Υπάρχει γυναικολόγος που δεν συστήνει Utrogestan?

Adreas · 10 Νοεμβρίου,2011

Official reprint from UpToDate www.uptodate.com

Progesterone: Drug information

(For additional information see "Progesterone: Patient drug information")

ALERT: U.S. Boxed WarningThe FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.

U.S. Brand Names

Crinone;
Endometrin;
First™-Progesterone VGS 100;
First™-Progesterone VGS 200;
First™-Progesterone VGS 25;
First™-Progesterone VGS 400;
First™-Progesterone VGS 50;
Prochieve [DSC];
Prometrium

Pharmacologic Category

Progestin

Dosing: AdultFemales:

Amenorrhea: I.M.: 5-10 mg/day for 6-8 consecutive days

Amenorrhea, secondary:

Intravaginal gel: 45 mg (4% gel) every other day for 6 doses; if response is inadequate, may increase to 90 mg (8% gel) at same schedule

Oral: 400 mg every evening for 10 days

ART in patients who require progesterone supplementation:

Intravaginal gel: 90 mg (8% gel) once daily. If pregnancy occurs, may continue treatment for 10-12 weeks.

Intravaginal tablet: 100 mg 2-3 times daily starting at oocyte retrieval and continuing for up to 10 weeks.

ART in patients with partial or complete ovarian failure:

Intravaginal gel: 90 mg (8% gel) twice daily. If pregnancy occurs, continue treatment for 10-12 weeks.

Endometrial hyperplasia prevention (in postmenopausal women with a uterus who are receiving daily conjugated estrogen tablets): Oral: 200 mg as a single daily dose every evening for 12 days sequentially per 28-day cycle

Functional uterine bleeding: I.M.: 5-10 mg/day for 6 doses

Dosing: GeriatricRefer to adult dosing.

Dosage Forms: U.S.Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, oral:

Prometrium: 100 mg, 200 mg [contains peanut oil]

Gel, vaginal:

Crinone: 4% (1.45 g) [contains palm oil; 45 mg/dose]

Crinone: 8% (1.45 g) [contains palm oil; 90 mg/dose]

Prochieve: 4% (1.45 g [DSC]) [contains palm oil; 45 mg/dose]

Prochieve: 8% (1.45 g [DSC]) [contains palm oil; 90 mg/dose]

Injection, oil: 50 mg/mL (10 mL)

Powder, for prescription compounding [micronized]: USP: 100% (10 g, 25 g, 100 g)

Powder, for prescription compounding [wettable]: USP: 100% (10 g [DSC], 25 g [DSC], 100 g [DSC])

Suppository, vaginal [compounding kit]:

First™-Progesterone VGS 25: 25 mg (30s)

First™-Progesterone VGS 50: 50 mg (30s)

First™-Progesterone VGS 100: 100 mg (30s)

First™-Progesterone VGS 200: 200 mg (30s)

First™-Progesterone VGS 400: 400 mg (30s)

Tablet, vaginal:

Endometrin: 100 mg

Generic Equivalent Available: U.S.Yes: Injection, powder

AdministrationI.M.: Administer deep I.M. only

Intravaginal:

Vaginal gel: (A small amount of gel will remain in the applicator following insertion): Administer into the vagina directly from sealed applicator. Remove applicator from wrapper; holding applicator by thickest end, shake down to move contents to thin end; while holding applicator by flat section of thick end, twist off tab; gently insert into vagina and squeeze thick end of applicator.

For use at altitudes above 2500 feet: Remove applicator from wrapper; hold applicator on both sides of bubble in the thick end; using a lancet, make a single puncture in the bubble to relieve air pressure; holding applicator by thickest end, shake down to move contents to thin end; while holding applicator by flat section of thick end, twist off tab; gently insert into vagina and squeeze thick end of applicator.

Vaginal tablet: Insert tablet in vagina using disposable applicator provided.

Oral capsule: For patients who experience difficulty swallowing the capsules, taking with a full glass of water in the standing position may be beneficial.

UseOral: Prevention of endometrial hyperplasia in nonhysterectomized, postmenopausal women who are receiving conjugated estrogen tablets; secondary amenorrhea

I.M.: Amenorrhea; abnormal uterine bleeding due to hormonal imbalance

Intravaginal gel: Part of assisted reproductive technology (ART) for infertile women with progesterone deficiency; secondary amenorrhea

Vaginal tablet: Part of ART for infertile women with progesterone deficiency

Adverse Reactions SignificantInjection (I.M.):

Cardiovascular: Cerebral edema, cerebral thrombosis, edema

Central nervous system: Depression, fever, insomnia, somnolence

Dermatologic: Acne, allergic rash (rare), alopecia, hirsutism, pruritus, rash, urticaria

Endocrine & metabolic: Amenorrhea, breakthrough bleeding, breast tenderness, galactorrhea, menstrual flow changes, spotting

Gastrointestinal: Nausea, weight gain/loss

Genitourinary: Cervical erosion changes, cervical secretion changes

Hepatic: Cholestatic jaundice

Local: Injection site: Irritation, pain, redness

Ocular: Optic neuritis, retinal thrombosis

Respiratory: Pulmonary embolism

Miscellaneous: Anaphylactoid reactions

Oral capsule (percentages reported when used in combination with or cycled with conjugated estrogens):

>10%:

Central nervous system: Headache (16% to 31%), dizziness (15% to 24%), depression (19%)

Endocrine & metabolic: Breast tenderness (27%), breast pain (6% to 16%)

Gastrointestinal: Abdominal pain (10% to 20%), abdominal bloating (8% to 12%)

Genitourinary: Urinary problems (11%)

Neuromuscular & skeletal: Joint pain (20%), musculoskeletal pain (12%)

Miscellaneous: Viral infection (12%)

5% to 10%:

Cardiovascular: Chest pain (7%)

Central nervous system: Fatigue (8%), irritability (8%), worry (8%)

Gastrointestinal: Nausea/vomiting (8%), diarrhea (7% to 8%)

Genitourinary: Vaginal discharge (10%)

Respiratory: Cough (8%)

<5%: Breast biopsy, breast cancer, cholecystectomy, constipation

Postmarketing and/or case reports: Aggression, alopecia, anaphylactic reaction, arthralgia, asthma, blurred vision, choking, cholestasis, cholestatic hepatitis, circulatory collapse, confusion, consciousness depressed/loss, convulsion, depersonalization, diplopia, disorientation, drunk feeling, dysarthria, dysphagia, dyspnea, endometrial carcinoma, facial edema, feeling abnormal, gait abnormal, hepatic enzymes increased, hepatic failure, hepatic necrosis, hepatitis, hyperglycemia, hyper-/hypotension, hypersensitivity, jaundice, liver function tests increased, menorrhagia, menstrual disorder, metrorrhagia, muscle cramps, ovarian cyst, pancreatitis (acute), paresthesia, pruritus, sedation, slurred speech, stupor, suicidal ideation, syncope, tachycardia, throat tightness, TIA, tinnitus, tongue swelling, urticaria, vertigo, visual disturbance, walking difficulty, weight gain/loss

Vaginal gel (percentages reported with ART); also refer to oral capsule reactions listing for additional effects noted with progesterone:

>10%:

Central nervous system: Somnolence (27%), headache (13% to 17%), nervousness (16%), depression (11%)

Endocrine & metabolic: Breast enlargement (40%), breast pain (13%), libido decreased (11%)

Gastrointestinal: Constipation (27%), nausea (7% to 22%), cramps (15%), abdominal pain (12%)

Genitourinary: Perineal pain (17%), nocturia (13%)

5% to 10%:

Central nervous system: Pain (8%), dizziness (5%)

Gastrointestinal: Diarrhea (8%), bloating (7%), vomiting (5%)

Genitourinary: Vaginal discharge (7%), dyspareunia (6%), genital moniliasis (5%), genital pruritus (5%)

Neuromuscular & skeletal: Arthralgia (8%)

Vaginal tablet (percentages reported with ART); also refer to oral capsule reactions listing for additional effects noted with progesterone:

>10%:

Gastrointestinal: Abdominal pain (12%)

Miscellaneous: Post-oocyte retrieval pain (25% to 28%)

1% to 10%:

Central nervous system: Headache (3% to 4%), fatigue (2% to 3%)

Endocrine & metabolic: Ovarian hyperstimulation syndrome (7%)

Gastrointestinal: Nausea (7% to 8%), abdominal distension (4%), constipation (2% to 3%), vomiting (2% to 3%)

Genitourinary: Uterine spasm (3% to 4%), vaginal bleeding (3%), urinary tract infection (1% to 2%)

<1%: Burning, discomfort, itching, peripheral edema, urticaria, vaginal irritation

ContraindicationsHypersensitivity to progesterone or any component of the formulation; undiagnosed abnormal vaginal bleeding; history of or current thrombophlebitis or venous thromboembolic disorders (including DVT, PE); history of, active or recent (within 1 year) arterial thromboembolic disease (eg, stroke, MI); history of or known or suspected carcinoma of the breast or genital organs; hepatic dysfunction or disease; missed abortion or ectopic pregnancy; diagnostic test for pregnancy; capsules are also contraindicated for use during pregnancy

Warnings/PrecautionsBoxed warnings:

• Breast cancer: See “Concerns related to adverse effects” below.

• Cardiovascular disease: See “Disease-related concerns” below.

• Dementia: See “Concerns related to adverse effects” below.

Concerns related to adverse effects:

• Breast cancer: [u.S. Boxed Warning]: An increased risk of invasive breast cancer was observed in postmenopausal women using conjugated equine estrogens (CEE) in combination with medroxyprogesterone acetate (MPA). An increase in abnormal mammograms has also been reported with estrogen and progestin therapy.

• CNS effects: Patients should be warned that progesterone might cause transient dizziness or drowsiness during initial therapy.

• Dementia: [u.S. Boxed Warning]: The risk of dementia may be increased in postmenopausal women; progestins used in combination with estrogen should not be used to prevent dementia. Increased incidence was observed in women ≥65 years of age taking CEE alone or in combination with MPA.

• Endometrial carcinoma: Unopposed estrogens may increase the risk of endometrial carcinoma in postmenopausal women with an intact uterus. Risk appears to be associated with long-term use. The use of a progestin should be considered when administering estrogens to postmenopausal women with an intact uterus. Adequate diagnostic measures, including endometrial sampling (if indicated), should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.

• Ovarian cancer: Postmenopausal estrogen therapy and combined estrogen/progesterone therapy may increase the risk of ovarian cancer; however, the absolute risk to an individual woman is small. Although results from various studies are not consistent, risk does not appear to be significantly associated with the duration, route, or dose of therapy. In one study, the risk decreased after 2 years following discontinuation of therapy .

• Retinal vascular thrombosis: Discontinue pending examination in cases of sudden partial or complete vision loss, sudden onset of proptosis, diplopia, or migraine; discontinue permanently if papilledema or retinal vascular lesions are observed on examination.

Disease-related concerns:

• Cardiovascular disease: [u.S. Boxed Warning]: Progestins used in combination with estrogen should not be used to prevent cardiovascular disease. Use caution with cardiovascular disease or dysfunction. Progestins used in combination with estrogen may increase the risks of hypertension, myocardial infarction (MI), stroke, pulmonary emboli (PE), and deep vein thrombosis; incidence of these effects was shown to be significantly increased in postmenopausal women using CEE in combination with MPA. Similar risk should be assumed with other progestins.

• Depression: Use with caution in patients with a history of depression.

• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, diabetes, or renal dysfunction.

Special populations:

• Pediatrics: Not for use prior to menarche.

• Surgical patients: Whenever possible, progestins in combination with estrogens should be discontinued at least 4-6 weeks prior to and for 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

Dosage form specific issues:

• Benzyl alcohol: Some products may contain benzyl alcohol.

• Palm oil: Some products may contain palm oil.

• Peanut oil: Some products may contain peanut oil.

• Sesame oil: Some products may contain sesame oil.

Other warnings/precautions:

• Risks vs. benefits: Before prescribing progestin therapy in combination with estrogen to postmenopausal women, the risks and benefits must be weighed for each patient. Women should be informed of these risks and benefits, as well as possible effects of estrogen when added to progestin therapy. Progestins with or without estrogen should be used for shortest duration possible consistent with treatment goals. Conduct periodic risk:benefit assessments.

Metabolism/Transport EffectsSubstrate of CYP1A2 (minor), 2A6 (minor), 2C9 (minor), 2C19 (major), 2D6 (minor), 3A4 (major); Inhibits CYP2C9 (weak), CYP2C19 (weak), CYP3A4 (weak), P-glycoprotein

Drug Interactions

(For additional information: Launch Lexi-Interact™ Drug Interactions Program )

Aminoglutethimide: May increase the metabolism of Progestins. Management: Progestin-containing contraceptives are not recommended; consider the use of alternative, nonhormonal contraceptives. Risk D: Consider therapy modification

Colchicine: P-Glycoprotein Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Dabigatran Etexilate: P-Glycoprotein Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. According to Canadian labeling, dabigatran dose for prevention of venous thromboembolism post hip or knee replacement should be reduced to 150 mg/day in patients receiving amiodarone, verapamil, or quinidine. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Everolimus: P-Glycoprotein Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification

Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

P-Glycoprotein Substrates: P-Glycoprotein Inhibitors may increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Rivaroxaban: P-Glycoprotein Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy

Silodosin: P-Glycoprotein Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Topotecan: P-Glycoprotein Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Ethanol/Nutrition/Herb InteractionsFood: Food increases oral bioavailability.

Herb/Nutraceutical: St John's wort may decrease progesterone levels. Herbs with progestogenic properties may enhance the adverse/toxic effects of progestin; example herbs include bloodroot, chasteberry, damiana, oregano, yucca.

Pregnancy Risk FactorB (Prometrium, per manufacturer); none established for vaginal gel, vaginal tablet, or injection (show table)

Pregnancy Implications: Adverse events were not observed following oral administration in animal reproduction studies. There is an increased risk of minor birth defects in children whose mothers take progesterones during the first 4 months of pregnancy. Hypospadias has been reported in male and mild masculinization of the external genitalia has been reported in female babies exposed during the first trimester. Cleft lip, cleft palate, congenital heart disease, patent ductus arteriosus, ventricular septal defect, intrauterine death, and spontaneous abortion have been noted in case reports following use of oral progesterone during pregnancy. High doses of progesterone would be expected to impair fertility. According to the American College of Obstetricians and Gynecologists, additional studies are needed to evaluate the use of progesterone to reduce the risk of preterm birth. If needed, use should be restricted to women with history of previous spontaneous abortion at <37 weeks. The vaginal gel and tablet are indicated for use in ART. The oral capsules are contraindicated for use during pregnancy.

LactationEnters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)

Pricing: U.S. (www.drugstore.com)Capsules (Prometrium)

100 mg (30): $68.99

200 mg (30): $121.99

Gel (Prochieve)

4% (26.1): $159.99

8% (26.1): $221.00

INST (Endometrin)

100 mg (21): $157.41

Oil (Progesterone)

50 mg/mL (10): $37.99

Monitoring ParametersRoutine physical examination that includes blood pressure and Papanicolaou smear, breast exam, mammogram. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding. Signs and symptoms of thromboembolic disorders, vision changes

Canadian Brand Names

Crinone;
Prometrium

International Brand Names

Crinone (AR, AU, BE, CH, CL, DE, DK, ES, FI, GB, GR, HK, ID, IE, IL, IT, KP, MY, NO, PH, RU, SE, SG, TR, TW, UY, VE);
Cyclogest (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, MY, OM, PK, QA, SA, SG, SY, YE, ZA);
Cygest (ID);
Endometrin (HK, IL);
Estima Ge (FR);
Gepromi (MX);
Geslutin (CO, DO, GT, HN, MX, NI);
Geslutin PNM (EC, PE);
Glanducorpin (HU);
Gynprogest (PY);
Luteina (PL);
Lutogynestryl Fuerte (PE);
Mafel (AR);
Naturogest (IN);
Progendo (CN);
Progering (PE);
Progestan (NL);
Progestin (GT, NI, PA, SV);
Progestogel (HK, LU);
Utrogestan (AT, BE, BG, BR, CH, CZ, ES, FR, GB, HU, KP, LU, MX, MY, PT, SG, UY)

Mechanism of ActionNatural steroid hormone that induces secretory changes in the endometrium, promotes mammary gland development, relaxes uterine smooth muscle, blocks follicular maturation and ovulation, and maintains pregnancy. When used as part of an ART program in the luteal phase, progesterone supports embryo implantation.

Pharmacodynamics/KineticsAbsorption: Vaginal gel: Prolonged

Absorption half-life: 25-50 hours

Protein binding: Albumin (50% to 54%) and cortisol-binding protein (43% to 48%)

Metabolism: Hepatic to metabolites

Half-life elimination: Vaginal gel: 5-20 minutes

Time to peak: Oral: Within 3 hours; I.M.: ~8 hours; Vaginal tablet: ~17-24 hours

Excretion: Urine, bile, feces

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REFERENCES

American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89. [PubMed 11533352]
American College of Obstetricians and Gynecologists, Society for Maternal Fetal Medicine Publications Committee, ACOG Committee Opinion No. 419 (replaces No. 291, November 2003), “Use of Progesterone to Reduce Preterm Birth,”Obstet Gynecol, 2008, 112(4):963-5. [PubMed 18827143]
Doody K, Shamma N, Paulson R, et al. “Endometrin for Luteal Phase Support in a Randomized, Controlled, Open-Label, Prospective IVF Clinical Trial Using a Combination of Menopur and Bravelle,” Fertil Steril, 2007, 87(4 Suppl 2):24 [abstract]. [PubMed 17081533]
Mψrch LS, Lψkkegaard E, Andreasen AH, et al, “Hormone Therapy and Ovarian Cancer,” JAMA, 2009, 302(3):298-305. [PubMed 19602689]
Ng EH, Chan CC, Tang OS, et al, “A Randomized Comparison of Side Effects and Patient Convenience Between Cyclogest Suppositories and Endometrin Tablets Used for Luteal Phase Support in IVF Treatment,” Eur J Obstet Gynecol Reprod Biol, 2007, 131(2):182-8. [PubMed 16920249]

Adreas · 10 Νοεμβρίου,2011

Μου προξένησαν εντύπωση τα παρακάτω στο τελευταίο ποστ, οπότε βάζω και την αυτόματη μετάφραση του Google

• Breast cancer: [U.S. Boxed Warning]: An increased risk of invasive breast cancer was observed in postmenopausal women using conjugated equine estrogens (CEE) in combination with medroxyprogesterone acetate (MPA). An increase in abnormal mammograms has also been reported with estrogen and progestin therapy.

• Ο καρκίνος του μαστού: [ΗΠΑ Συσκευασμένο Προειδοποίηση]: Αυξημένος κίνδυνος διηθητικού καρκίνου του μαστού παρατηρήθηκε σε μετεμμηνοπαυσιακές γυναίκες που χρησιμοποιούν συζευγμένο οιστρογόνο αλόγου (CEE) σε συνδυασμό με οξική μεδροξυπρογεστερόνη (MPA). Η αύξηση της ανώμαλη μαστογραφίες έχει επίσης αναφερθεί με θεραπεία με οιστρογόνα και προγεστερόνη.</SPAN>

Pregnancy Implications: Adverse events were not observed following oral administration in animal reproduction studies. There is an increased risk of minor birth defects in children whose mothers take progesterones during the first 4 months of pregnancy. Hypospadias has been reported in male and mild masculinization of the external genitalia has been reported in female babies exposed during the first trimester. Cleft lip, cleft palate, congenital heart disease, patent ductus arteriosus, ventricular septal defect, intrauterine death, and spontaneous abortion have been noted in case reports following use of oral progesterone during pregnancy. High doses of progesterone would be expected to impair fertility. According to the American College of Obstetricians and Gynecologists, additional studies are needed to evaluate the use of progesterone to reduce the risk of preterm birth. If needed, use should be restricted to women with history of previous spontaneous abortion at <37 weeks. The vaginal gel and tablet are indicated for use in ART. The oral capsules are contraindicated for use during pregnancy.

Επιπτώσεις Εγκυμοσύνη: Οι ανεπιθύμητες ενέργειες που δεν παρατηρήθηκαν μετά από του στόματος χορήγηση σε μελέτες αναπαραγωγής σε ζώα. Υπάρχει αυξημένος κίνδυνος των ανήλικων συγγενών ανωμαλιών σε παιδιά των οποίων οι μητέρες λαμβάνουν προγεστερόνες κατά τους πρώτους 4 μήνες της εγκυμοσύνης. Υποσπαδίας έχει αναφερθεί σε άνδρες και ήπια αρρενοποίηση των εξωτερικών γεννητικών οργάνων έχει αναφερθεί σε θηλυκά μωρά που εκτίθενται κατά τη διάρκεια του πρώτου τριμήνου. Λαγόχειλο, λυκόστομα, συγγενή καρδιοπάθεια, ανοιχτός αρτηριακός πόρος, έλλειμμα μεσοκοιλιακού διαφράγματος, ενδομήτριο θάνατο, και την αυτόματη αποβολή που έχουν παρατηρηθεί σε αναφορές περιστατικών μετά τη χρήση του από του στόματος προγεστερόνης κατά τη διάρκεια της εγκυμοσύνης. Οι υψηλές δόσεις της προγεστερόνης αναμένεται να βλάψει τη γονιμότητα. Σύμφωνα με το Αμερικανικό Κολέγιο Μαιευτήρων και Γυναικολόγων, οι συμπληρωματικές μελέτες που απαιτούνται για την αξιολόγηση της χρήσης της προγεστερόνης στην μείωση του κινδύνου πρόωρου τοκετού. Εάν χρειαστεί, η χρήση πρέπει να περιορίζεται σε γυναίκες με ιστορικό προηγούμενων αυτόματων αποβολών σε <37 εβδομάδες. Το κολπικό τζελ και δισκίο ενδείκνυνται για χρήση στην τέχνη. Οι κάψουλες από το στόμα αντενδείκνυται για χρήση κατά τη διάρκεια της εγκυμοσύνης.</SPAN>

Cristy · 10 Νοεμβρίου,2011

Νάσαι καλά βρε aantonie, μας ανοίγεις τα μάτια.

Τουλάχιστον εγώ θα ζητήσω και εξέταση προγεστερόνης μαζί με τη χοριακή την επόμενη φορά, (που εύχομαι να υπάρξει).

Παραθέτω και μια χρήσιμη πληροφορία που άντλησα από το δικτυακό τόπο:

http://www.clinical.bioiatriki.gr/analysis/pdfs/b73.pdf

Σε κύηση τιμές προγεστερόνης πάνω από

20ng/ml υποδηλώνουν φυσιολογική εγκυμοσύνη

ενώ τιμές κάτω από 8ng/ml είναι συμβατές με

παλίνδρομη ή έκτοπη κύηση.

Μέθοδος

• RΙΑ.

Προετοιμασία ασθενούς και δείγματος

Καμία.

Ορός.

Σημειώνεται η τελευταία έμμηνος ρύση.

Φυσιολογικές τιμές

Άνδρες <1,6ng/ml

Γυναίκες

Παραγωγική Φάση 0,2-1,0ng/ml

Ωχρινική Φάση 3,1-31ng/ml

Παιδιά <0,5ng/ml

newbie G · 10 Νοεμβρίου,2011

Εγώ μένω στο τελευταίο: "The vaginal gel and tablet are indicated for use in ART"

Το ART τι είναι; Γιατί δε νομίζω να είναι "τέχνη" :rolleyes:

Adreas · 10 Νοεμβρίου,2011

Management of couples with recurrent pregnancy loss

Authors

Togas Tulandi, MD, MHCM

Haya M Al-Fozan, MD

Section Editor

Charles J Lockwood, MD

Deputy Editor

Vanessa A Barss, MD

Disclosures

Last literature review version 19.2:Μάϊος 2011 |This topic last updated:Μάϊος 16, 2011 (More)

INTRODUCTION — High quality data on management of recurrent pregnancy loss (RPL) are limited; therefore, therapeutic recommendations are largely based upon clinical experience and data from observational studies. Nevertheless, the prognosis for a successful future pregnancy is generally good: the overall live birth rates after normal and abnormal diagnostic evaluations for RPL are 77 and 71 percent, respectively [1].

Therapeutic intervention is guided by the underlying cause of RPL. In all cases, emotional support is important in caring for these often anxious couples, and may enhance therapeutic success [2-4].

Management of RPL will be discussed here. Causes and evaluation of RPL are reviewed separately. (See "Definition and etiology of recurrent pregnancy loss" and "Evaluation of couples with recurrent pregnancy loss".)

PARENTAL KARYOTYPE ABNORMALITY — Couples in whom chromosomal abnormalities are discovered in one or both partners or the abortus are generally referred for genetic counseling [5]. They should receive information regarding the probability of having a chromosomally normal or abnormal conception in the future. In the latter case, the risk of miscarriage and bearing a chromosomally abnormal offspring who may be phenotypically normal or abnormal and a carrier of a chromosomal defect should be discussed. The magnitude of these risks varies according to the specific chromosomal abnormality and the sex of the carrier parent. (See "Chromosomal translocations, deletions, and inversions" and "Cytogenetic abnormalities in the embryo, fetus, and infant".)

Couples with karyotypic abnormalities may choose to undergo prenatal genetic studies, such as amniocentesis or chorionic villus sampling, to determine the fetal karyotype. Pregnancy termination is an option if the fetus is affected. In vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD) can be used to avoid transfer and implantation of an affected embryo [6-8]. PGD improves the pregnancy outcome of translocation carriers with a history of repeated pregnancy loss [9]. On the other hand, this procedure reduces the live birth rate after IVF if preimplantation testing is performed solely because of advanced maternal age [10]. (See "Preimplantation genetic diagnosis".)

Gamete donation (egg or sperm), surrogacy, and adoption are methods of preventing conception of an affected embryo. The choice depends upon the specific abnormality and parental preference. (See individual topic reviews on these topics).

UTERINE ABNORMALITIES — Uterine abnormalities are managed surgically if the defect is a surgically correctable cause of pregnancy loss, such as a uterine septum, intrauterine adhesions, and submucosal myoma. These conditions can be treated hysteroscopically. (See "Surgical management of congenital uterine anomalies" and "Intrauterine adhesions" and "Vaginal myomectomy for a prolapsed uterine leiomyoma (fibroid)".)

There are no randomized, controlled studies evaluating pregnancy outcome after surgical correction of uterine anomalies. In a classic observational series, repair of bicornuate and septate uteri reduced the abortion rate from 84 percent (before surgery) to 12 percent (after surgery) [11]. Others have reported successful pregnancy in 85 to 90 percent of women after hysteroscopic resection of a uterine septum or lysis of adhesions [12-17]. The problem with all of these studies is use of patients as their own controls.

Women with recurrent second trimester pregnancy losses may benefit from placement of a cervical cerclage. The value of prophylactic cervical cerclage in women with a uterine anomaly, but no history of second trimester pregnancy loss, is controversial [18]. We do not advocate prophylactic cervical cerclage in women with no history of cervical insufficiency. (See "Cervical insufficiency" and "Transvaginal cervical cerclage".)

A gestational carrier is an option for women with irreparable uterine defects. (See "Gestational carrier pregnancy".)

ANTIPHOSPHOLIPID SYNDROME — Drugs such as aspirin and heparin appear to improve pregnancy outcome in women with antiphospholipid syndrome who have recurrent fetal losses. There is controversy about the benefit of such therapy in selected women with recurrent embryonic losses. (See "Management of pregnant women with antiphospholipid antibodies or the antiphospholipid syndrome".)

SUSPECTED IMMUNOLOGIC DYSFUNCTION — Although no alloimmune mechanism has been proven to cause RPL, several immunologic treatments have been advocated to improve the live birth rate in women with previous unexplained RPL. None are effective, and some appear to be harmful [19-25].

Immunotherapy — Systematic reviews have consistently found no beneficial effect of immunotherapy for treatment of RPL [20,22,26,27]. The general findings are illustrated by the following two examples:

A systematic review of 20 trials of high quality showed that immunotherapy did not result in a statistically significant improvement in live births compared to untreated controls [20]. Four types of immunotherapy were evaluated: paternal cell immunization (OR 1.23, 95% CI 0.89-1.70; 12 studies including 641 participants); third party donor cell immunization (OR 1.39, 95% CI 0.68-2.82; three studies including 156 participants); trophoblast membrane infusion (OR 0.40, 95% CI 0.11-1.45; one study including 37 participants); and intravenous immune globulin (OR 0.98, 95% CI 0.61-1.58; eight studies including 303 participants).
Another systematic review evaluated three randomized and two cohort trials of immunotherapy treatment specifically in patients who failed IVF; a total of 373 patients were involved in these trials [26]. Patients treated with IVIG showed a consistently higher live birth rate than untreated controls; this benefit was statistically significant when the trial results were pooled in meta-analysis. However, there were many differences among these trials, such as the preparations used, the timing of the intervention (preconception, postconception, both), and dosage, as well as the immunological abnormalities of the patients. In addition, some controls received heparin and aspirin while others did not receive any therapy. Thus, appropriate use of this therapy remains unclear.

Immune therapy of RPL should be considered experimental, and used only in the setting of a clinical trial regulated by an Institutional Review Board.

Glucocorticoids — Glucocorticoids have several anti-inflammatory effects, including suppression of natural killer cell activity, but do not appear to be effective for preventing RPL. This was illustrated by a trial in which 202 women with RPL and a variety of autoantibodies (antinuclear, anti-DNA, antilymphocyte, anticardiolipin, lupus anticoagulant) were randomly assigned to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy [24]. The two groups did not have a statistically significant difference in rate of live birth (66 and 56 percent, respectively).

Oral administration of glucocorticoids for treatment of RPL has been abandoned because of uncertain efficacy and a clearly demonstrable increase in complications, such as preterm premature rupture of membranes, gestational diabetes, and maternal hypertension [23,24]. Alternative methods of glucocorticoid treatment, which are under investigation, may be safer [25].

THYROID DYSFUNCTION AND DIABETES MELLITUS — Women with overt thyroid disease or diabetes mellitus should be treated, as medically appropriate, since these disorders can result in serious sequelae. (See "Overview of medical care in adults with diabetes mellitus" and "Treatment of Graves' hyperthyroidism" and "Treatment of hypothyroidism" and "Subclinical hypothyroidism".)

Women with elevated serum thyroid peroxidase antibody concentrations are at high risk of developing hypothyroidism in the first trimester and autoimmune thyroiditis postpartum, and should be followed appropriately [28]. Euthyroid women with high serum thyroid peroxidase antibody concentrations may benefit from treatment with thyroid hormone during pregnancy as this therapy may reduce the risk of miscarriage and preterm birth. In a randomized trial, administration of levothyroxine (median dose 50 mcg daily) to early pregnant euthyroid women with positive thyroid peroxidase antibodies decreased the miscarriage rate from 13.8 to 3.5 percent (RR 1.72, 95% CI 1.13-2.25) [29]. In addition, the incidence of premature deliveries in treated women was lower than in those who were not treated (7 versus 22.4 percent, RR 1.66, 95% CI 1.18-2.34). Further study is required to evaluate the efficacy of levothyroxine in women with RPL and positive thyroid peroxidase antibodies. (See "Overview of thyroid disease in pregnancy", section on 'Thyroid peroxidase antibodies'.)

POLYCYSTIC OVARY SYNDROME — The miscarriage rate in women with polycystic ovary syndrome (PCOS) is 20 to 40 percent, higher than the baseline rate in the general obstetric population [30]. Metformin has been used in women with PCOS to decrease this risk, but the effectiveness of this approach is unproven. (See "Metformin for treatment of the polycystic ovary syndrome", section on 'Spontaneous abortion'.)

HYPERPROLACTINEMIA — Normal circulating levels of prolactin may play an important role in maintaining early pregnancy. A study of 64 hyperprolactinemic women with RPL randomly assigned to bromocriptine therapy or no bromocriptine found treatment was associated with a significantly higher rate of successful pregnancy (86 versus 52 percent) [31]. Prolactin levels during early pregnancy were significantly greater in women who miscarried. We suggest treatment of women with hyperprolactinemia and RPL, even in the absence of overt hypogonadism. (See "Treatment of hyperprolactinemia due to lactotroph adenoma and other causes".)

THROMBOPHILIA — Anticoagulation of women with certain inherited thrombophilias may improve maternal outcome (eg, prevention of venous thromboembolism), but does not appear to prevent pregnancy loss. These issues are discussed separately. (See "Inherited thrombophilias in pregnancy".)

UNEXPLAINED RPL — After evaluation, RPL remains unexplained in approximately one-half of couples. Nevertheless, the chance of a live birth is good, ie, over 50 percent with no intervention [32]. This rate must be considered in evaluating therapies for unexplained RPL.

Treatments that have been offered to couples with unexplained RPL, ranked in order of low to high risk, simplicity, and expense to the patient, include:

Lifestyle modification — Epidemiological studies suggest that lifestyle modifications can increase fertility potential, although these have not been definitively tested in randomized trials. These modifications include eliminating use of tobacco products, alcohol, and caffeine and reduction in body mass index (for obese women). (See "Optimizing natural fertility in couples planning pregnancy".)

Progesterone — Large randomized trials demonstrating the efficacy of progesterone treatment in RPL are lacking, but the drug is commonly prescribed for this indication. Meta-analyses of available randomized and semi-randomized trials of progesterone versus placebo or no treatment in women with unexplained RPL have shown a significant benefit (risk of RPL with progesterone OR 0.4 to 0.5) [33,34]. However, the use of progesterone to prevent RPL remains controversial because of the small total number of women treated with progesterone in these trials (<140), wide confidence intervals in most trials, and significant methodological problems in study design. Large, well-designed randomized trials are needed.

We typically prescribe progesterone (100 mg twice daily, vaginally) as empiric treatment of unexplained RPL. It is started three days after the LH surge, so as not to inhibit ovulation, and continued until 10 weeks of gestation, when placental progesterone production should be fully functional. Alternatively, progesterone in gel (90 mg vaginally once daily) or micronized progesterone (100 mg orally, two to three tablets per day) can be administered. The therapeutic effect of progesterone may be related to immune modulation [35].

Aspirin with or without heparin — A large randomized trial found that neither aspirin alone nor aspirin plus heparin improved the live-birth rate of women with unexplained RPL [36]. In this trial, 364 women with unexplained RPL after a thorough evaluation were randomly assigned to receive daily aspirin (80 mg), aspirin plus nadroparin (2850 international units), or placebo. Aspirin or placebo was begun preconceptionally and nadroparin was started as soon as a viable pregnancy was documented by ultrasound. Among the 299 women who became pregnant, the live-birth rates for combination therapy, aspirin alone, and placebo were not significantly different: 69, 62, and 67 percent, respectively.

Similarly, another trial randomly assigned 294 women with ≥2 consecutive unexplained pregnancy losses at ≤24 weeks to treatment with enoxaparin and low dose aspirin or no treatment; both groups received intensive pregnancy surveillance [37]. Medical therapy did not reduce the rate of pregnancy loss, which was 22 percent with drug treatment and 20 percent without it.

Human chorionic gonadotropin — Human chorionic gonadotropin (hCG) therapy during early gestation may be useful in preventing miscarriage since endogenous hCG is known to play a critical role in the establishment of pregnancy [24]. A systematic review of four trials involving 180 women with RPL found hCG therapy was associated with a significantly reduced risk of miscarriage (OR 0.26, 95% CI 0.14-0.52), particularly in women with oligomenorrhea [38]. However, there were important methodological weaknesses in two of these studies. To date, there is insufficient evidence to recommend the use of hCG to prevent pregnancy loss in women with a history of unexplained RPL. Large randomized controlled trials are needed.

Human menopausal gonadotropin — An observational study reported that controlled ovarian stimulation via human menopausal gonadotropin (hMG) administration appeared effective for treatment of endometrial defects in women with RPL [39]. The mechanism may be correction of a luteal phase defect or stimulation of a thicker endometrium, thus leading to a better implantation site. Our clinical experience supports the efficacy of this treatment.

Clomiphene citrate — By increasing serum FSH, clomiphene citrate increases follicular number and serum estradiol levels, which should lead to an increase in the number of corpora lutea and a higher midluteal progesterone concentration [40]. Two randomized trials comparing clomiphene to progesterone for treatment of inadequate luteal phase demonstrated similar pregnancy rates (20 to 30 percent) with each treatment [41,42]. Clomiphene, unlike progesterone, does not prolong the luteal phase, thereby lessening the anxiety and period of uncertainty of infertile couples concerning possible conception. Due to the anti-estrogen effect of clomiphene on the endometrium, we do not use clomiphene in women with RPL.

In vitro fertilization and preimplantation genetic diagnosis — Studies evaluating the value of in vitro fertilization (IVF) in women with RPL have yielded mixed results [43-46]. Embryos of women with unexplained RPL have a higher incidence of aneuploidy for chromosomes 13,16,18, 21, 22, X, and Y than embryos obtained from healthy women [47]. However, the value of preimplantation genetic screening in this setting has not been proven. (See "Preimplantation genetic diagnosis".)

Gestational carrier — Women with RPL or recurrent IVF implantation failures not associated with recurrent embryonic aneuploidy or obvious intrinsic gamete factors (eg, single gene defects, diminished oocyte and embryo quality) may consider use of a gestational carrier. Women who decide to pursue this route should undergo a thorough evaluation as to the etiology of the RPL or failed IVF. (See "Gestational carrier pregnancy".)

Oocyte donation — Poor quality oocytes may be responsible for 25 percent of pregnancy losses [48]. Ovum donation can overcome this problem and has been associated with a live birth rate of 88 percent in women with RPL [48]. The success of ovum donation, even when the male partner's sperm is utilized for fertilization, suggests the absence of a significant paternal contribution to the etiology of RPL. (See "Oocyte donation for assisted reproduction".)

Combination therapy — An observational study compared 50 pregnant women who were treated before and during pregnancy with prednisone (20 mg/day), progesterone (20 mg/day), aspirin (100 mg/day) and folate (5 mg every second day) with 52 women who were not treated during the same observation period [49]. The first trimester miscarriage rate was 19 percent in the treated group and 63 percent in the control group; this difference was not statistically significant. The live birth rate in the treated group and control groups was 77 and 35 percent, respectively (P = 0.04). With combined treatment of four agents, it is unclear which of the treatments was beneficial. The nonrandomized design and small number of cases also limits the usefulness of this study.

FUTURE PREGNANCY ISSUES — Women with a history of RPL who become pregnant may be at higher risk for developing fetal growth restriction and premature delivery, but not for gestational hypertension or diabetes. As an example, one study of 162 women with RPL who progressed beyond 24 weeks of gestation reported the rates of preterm delivery (13 percent), fetal growth restriction (13 percent), perinatal loss (2.5 percent) and cesarean delivery (36 percent) were significantly higher than those of the control group (approximately 4, 2, 1, and 17 percent, respectively) [50].

The greatest risk of recurrent loss occurs during the period up to the time of previous miscarriage. In women with recurrent early first trimester pregnancy loss, the presence of fetal cardiac activity is reassuring of subsequent viable delivery, although the pregnancy loss rate remains above that of the general population. A literature review of studies examining fetal loss rates after sonographic demonstration of fetal cardiac activity reported the rate of such losses in women with RPL was 5 to 22 percent compared to 7 to 15 percent in infertile populations and 3 to 6 percent in controls [51].

Second trimester pregnancy loss is significantly associated with recurrent second-trimester loss and future spontaneous preterm birth. After a second trimester pregnancy loss, one study reported 39 percent of women had a preterm delivery in their next pregnancy, 5 percent had a stillbirth, and 6 percent had a neonatal death [52]. In another study of 30 women with second trimester loss, the frequency of recurrent second trimester loss was 27 percent and the frequency of subsequent preterm birth was 33 percent [53].

Obstetrical management depends upon the underlying cause of RPL, if known. (See individual topic reviews).

SUMMARY AND RECOMMENDATIONS

Couples in whom chromosomal abnormalities are discovered in one or both partners or the abortus are generally referred for genetic counseling, which should include information about the probability of having a chromosomally normal or abnormal conception, and options for managing this risk. (See 'Parental karyotype abnormality' above.)
Given that resection of uterine septa, intrauterine adhesions, and submucosal myomas may be associated with a reduction pregnancy loss, we suggest surgical treatment of women with RPL and these abnormalities (Grade 2C). (See 'Uterine abnormalities' above.)
We recommend not using immunotherapy (Grade 1A) or glucocorticoids (Grade 1B) for treatment of RPL. These drugs are not effective and may be harmful. (See 'Immunotherapy' above.)
We suggest treatment of women with hyperprolactinemia and RPL (Grade 2B). (See 'Hyperprolactinemia' above.)
A variety of treatments have been offered to couples with unexplained RPL. We start with low risk, simple, and less expensive interventions and, if unsuccessful, move on to higher risk, more complex and expensive options. (See 'Unexplained RPL' above.)
Women with a history of RPL who become pregnant may be at higher risk for developing fetal growth restriction and premature delivery. Detection of fetal cardiac activity in early pregnancy is reassuring of subsequent viable delivery, although the pregnancy loss rate remains above that of the general population. (See 'Future pregnancy issues' above.)

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REFERENCES

Adreas · 10 Νοεμβρίου,2011

Prevention of spontaneous preterm birth

Author

Errol R Norwitz, MD, PhD

Section Editor

Charles J Lockwood, MD

Deputy Editor

Vanessa A Barss, MD

Disclosures

Last literature review version 19.2:Μάϊος 2011 |This topic last updated:Ιούνιος 9, 2011 (More)

INTRODUCTION — Twelve percent of births in the United States occur before 37 weeks and are considered preterm. Approximately 20 percent of preterm deliveries are iatrogenic; they are performed due to medical or obstetrical complications that are believed to put the health of the mother or fetus in jeopardy (eg, intrauterine growth restriction, preeclampsia, placenta previa, nonreassuring antenatal fetal testing). The remaining 80 percent of preterm deliveries are spontaneous, related to preterm labor or preterm premature rupture of the membranes.

Potential interventions for reducing the incidence of spontaneous preterm birth can be classified as primary (aimed at all women), secondary (aimed at eliminating or reducing risk in women with a previous preterm birth), or tertiary (aimed at preterm infants) [1]. While the ability of obstetrical care providers to identify women at risk for preterm birth has improved over the past three decades, application of primary and secondary interventions has not reduced the incidence of preterm delivery, which has actually increased. In the vast majority of cases, it is beyond the capabilities of obstetric medicine to prevent preterm delivery. Neonatal outcome, however, has improved during this interval as a result of widespread use of antenatal glucocorticoids and advances in neonatal care (eg, exogenous surfactant treatment, new methods of mechanical ventilation).

Strategies for the prevention of spontaneous preterm labor and delivery will be reviewed here. Other issues relating to preterm labor and birth are discussed separately (partial list):

(See "Pathogenesis of spontaneous preterm birth".)
(See "Risk factors for preterm labor and delivery".)
(See "Fetal fibronectin for prediction of preterm labor and delivery".)
(See "Inhibition of acute preterm labor".)

IDENTIFICATION OF RISK FACTORS FOR PRETERM BIRTH — In theory, identification of risk factors for preterm delivery before conception or in early pregnancy provides an opportunity for intervention to prevent this complication (table 1). However, many preterm births occur among women with no risk factors and there are few interventions that have been proven to prolong pregnancy in women at risk. (See "Risk factors for preterm labor and delivery".)

POTENTIALLY EFFECTIVE INTERVENTIONS

Supplemental progesterone — Progesterone supplementation to reduce spontaneous preterm birth has been studied in a variety of high risk populations [2]. The best evidence is for a reduction in risk of preterm birth in women with a history of prior preterm birth. There also appears to be a reduction in risk of preterm birth in women with a short cervix on ultrasound and possibly after arrested preterm labor, but the evidence is less robust. There is no evidence that progesterone supplementation is beneficial in other settings (eg, multiple gestation, preterm premature rupture of membranes) or that it reduces the risk of perinatal death [3]. The only adverse effect reported is a three-fold increase in risk of developing gestational diabetes in some studies [4,5], but this finding was not confirmed in analysis of data from another large study [6].

Progesterone preparations — The optimal progesterone formulation, route of delivery, and dose have not been determined. There is evidence from in vitro and animal research that the type of progestin, formulation, dose, and route of delivery have a significant impact on efficacy [7,8]. These factors likely played a role in the discordant findings reported in the trials discussed below.

The two types of progesterone are natural and synthetic. Natural progesterone is typically administered vaginally. The advantage of vaginal progesterone is its high uterine bioavailability since uterine exposure occurs before the first pass through the liver. It also has few systemic side effects, but vaginal irritation can be bothersome and the drug needs to be administered daily. Side effects include sleepiness, fatigue and headache [9,10]. The synthetic progesterone 17-alpha-hydroxyprogesterone is administered intramuscularly. Micronized progesterone is available for oral administration, but has only been administered vaginally for prevention of preterm birth [11].

In February 2011, an FDA-approved formulation of hydroxyprogesterone caproate (Makena™) became available commercially for use in women with a history of a prior spontaneous preterm birth. The FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate when obstetrically indicated, unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products [12]. Some pharmacies may elect to continue to compound the drug because of the significantly higher cost of the commercially available product ($690/dose versus $10 to 20/dose compounded). Standard contraindications to progesterone administration include past or present history of thromboembolic disorders, hormone-sensitive cancer, liver disease, or uncontrolled hypertension.

Dose and administration — The following progesterone formulations and doses can be used to reduce the risk of preterm birth [13]. There is no evidence that one approach is better than another, as comparative studies have not been performed.

Progesterone supplementation is begun between 160days and 206days weeks of gestation and continued until 366days weeks [14-18]. Early discontinuation of therapy appears to increase the risk of recurrent preterm birth.

Hydroxyprogesterone caproate: Administer 250 mg [14] intramuscularly each week, either as a generic formulation compounded locally or Makena®.
Natural progesterone: (the FDA has not reviewed the following preparations for treatment of preterm birth)

Crinone® or Prochieve® 8% (90 mg progesterone gel). Administer 90 mg vaginally each day via a prefilled applicator [19].
Endometrin® 100 mg vaginal tablet. Administer 100 mg [15] or 200 mg [20] vaginally each day.
Prometrium® 100 mg or 200 mg capsules. Administer 100 mg [15] or 200 mg [20] vaginally each day.

Clinical indications for progesterone supplementation

History of spontaneous preterm birth — Based on evidence of from meta-analyses, we recommend progesterone supplementation to women with a prior preterm birth [3,21-23]. We suggest limiting progesterone supplementation to women with a previous preterm delivery at less than 34 weeks. This recommendation is based on secondary analysis of data from a randomized trial by the Maternal Fetal Medicine Units Network that showed progesterone supplementation of women whose previous preterm birth was at ≥34 weeks of gestation resulted in similar rates of recurrent preterm delivery and a similar gestational age at delivery as those who received placebo [24]. Progesterone was more effective than placebo in women whose previous preterm birth was before 34 weeks. The American College of Obstetricians and Gynecologists recommends that progesterone supplementation be restricted to women with a singleton pregnancy and a previous history of spontaneous preterm birth [16].

In 2003, two large well-designed randomized controlled trials created a resurgence of interest in progesterone supplementation by providing the initial evidence of efficacy:

Maternal-Fetal Medicine Units Network trial — Meis and coinvestigators randomly assigned 459 patients with a documented history of spontaneous preterm delivery to weekly intramuscular injections of 17-alpha-hydroxyprogesterone caproate (250 mg) or placebo beginning at 16 to 20 weeks of gestation and continuing until 36 weeks [14]. Active prophylaxis significantly reduced the risk of delivery:

<37 weeks (36 versus 55 percent in the placebo group [RR, 0.66; 95% CI, 0.54-0.81]),
<35 weeks (21 versus 31 percent [RR, 0.67; 95% CI, 0.48-0.93])
<32 weeks (11 versus 20 percent [RR, 0.58; 95% CI, 0.37-0.91])
In addition, progesterone exposed infants had lower perinatal morbidity, with significantly reduced rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen. There was no evidence of virilization of female offspring, which was a theoretic concern of this therapy.

da Fonseca trial — da Fonseca and coinvestigators randomly assigned 142 women at high-risk for preterm delivery (based on at least one previous spontaneous preterm birth, prophylactic cervical cerclage, or uterine malformation) to daily supplementation with progesterone vaginal suppositories (100 mg) or placebo from 24 through 34 weeks of gestation [15]. Active prophylaxis significantly reduced the risk of delivery:

<37 weeks (14 versus 29 percent in the placebo group)
<34 weeks (3 versus 19 percent in the placebo group)
In addition, by monitoring all patients with an external tocodynamometer once a week for 60 minutes, the investigators were also able to demonstrate a significant difference in the frequency of spontaneous uterine contractions between the two groups.

Subsequently, meta-analyses of these and other randomized trials confirmed these findings: the preterm birth rate with use of progestational agents was 25 to 31 percent versus 33 to 47 percent in controls [3,21-23]. Statistically significant reductions in the clinical sequelae of preterm birth (perinatal mortality or prematurity-related morbidity) were not demonstrated consistently, likely because of lack of adequate power to evaluate these less common outcomes.

The effectiveness of progesterone supplementation for prevention of preterm birth is far from settled. The most recent and largest randomized trial of progesterone supplementation for prevention of recurrent preterm birth did not find a benefit.

O’Brien trial — In this trial, 659 women with a history of prior preterm birth were randomly assigned to self-administer progesterone gel (90 mg) or placebo vaginally each day from between 18 and 22 6/7ths weeks to 37 weeks of gestation [9]. Women with uterine anomalies and cervical cerclage or planned cervical cerclage were excluded.

Progesterone supplementation did not significantly reduce the frequency of preterm birth at any gestational age compared with placebo (for both groups, the rates of preterm birth ≤32, ≤35, and ≤37 weeks were about 10, 25, and 40 percent, respectively). There were no differences between groups for any maternal or neonatal outcome measure.

The reason for the discordance between this trial and other trials is unclear. Although progesterone gel was used instead of 17-alpha-hydroxyprogesterone caproate, both progesterone and the 17-alpha-hydroxyprogesterone caproate were effective in previous trials. Nevertheless, as discussed above, the type, dose, and route of administration of progesterone may have accounted for the disparity in results [7,8].

Although supplemental progesterone appears to be effective in preventing preterm birth in some high risk women, it should not be seen as a panacea. An analysis of 2002 national birth certificate data demonstrated that even if all eligible women received progesterone prophylaxis, it would only reduce the overall preterm birth rate in the United States by approximately 2 percent (from 12.1 to 11.8 percent) [25]. This is because only 22.5 percent of preterm births in 2002 were recurrent and prophylaxis only reduces the incidence of recurrent preterm birth by 33 percent.

Other situations where progesterone may be effective — There is limited high quality evidence regarding progesterone supplementation in women with other high risk conditions [26]. Some promising results in women with arrested preterm labor or short cervical length have been reported:

Arrested preterm labor — Progesterone supplementation after arrested preterm labor prolongs latency compared to no supplementation.

A randomized trial of 60 women who remained undelivered after an episode of preterm labor reported treatment with 17-alpha-hydroxyprogesterone caproate (341 mg twice weekly) was associated with less shortening of the cervix and a reduced rate of preterm delivery compared with observation alone [27].
A similar trial randomly assigned 70 women who remained undelivered after an episode of preterm labor to progesterone vaginal suppository (400 mg daily) or no intervention [28]. Progesterone maintenance therapy was associated with longer latency, fewer preterm births and complications of prematurity, and higher birth weight than expectant management, although some of the results did not reach statistical significance.

Short cervix — Data from randomized trials show that progesterone supplementation prolongs pregnancy in women with a short cervix. Sonographic measurement of cervical length in asymptomatic low or high risk women followed by progesterone treatment of women with short cervices may prove to be a useful approach to prevention of spontaneous preterm birth. (See "Cervical insufficiency", section on 'Incidental discovery of a short cervix at <24 weeks, no prior preterm birth'.)

In the largest randomized trial, 458 asymptomatic women found to have a short cervix (10 to 20 mm) at 19 to 24 weeks of gestation were randomly assigned to receive progesterone gel (90 mg) or a placebo daily until 37 weeks of gestation [19]. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks (8.9 [n = 21] versus 16.1 [n = 36] percent, RR 0.55, 95% CI 0.33-0.92). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1 versus 10.3 percent, RR 0.50, 95% CI 0.25-0.97) and 35 weeks (14.5 versus 23.3 percent, RR 0.62, 95% CI 0.42-0.92), respiratory distress syndrome (3.0 versus 7.6 percent, RR 0.39, 95% CI 0.17-0.92), any neonatal morbidity or mortality event (7.7 versus 13.5 percent, RR 0.57, 95% CI 0.33-0.99), and birth weight <1500 g (6.4 [15/234] versus 13.6 [30/220] percent, RR 0.47, 95% CI 0.26-0.85).
In another randomized trial, 250 asymptomatic women with a short cervix (≤15 mm) on ultrasound at 20 to 25 weeks of gestation were treated with either vaginal progesterone (200 mg each night) or placebo [20]. Progesterone administration significantly reduced the rate of spontaneous preterm birth (delivery before 34 weeks 19.2 versus 34.4 percent in controls, RR 0.54, 95% CI 0.36-0.86).
Findings from a small randomized trial also suggested progesterone supplementation (90 mg vaginally) was effective in preventing early preterm birth in women with sonographic evidence of a short cervix [29].

There is conflicting evidence as to whether progesterone treatment significantly attenuates further cervical shortening [27,30].

Clinical situations where progesterone has no proven efficacy — On the other hand, there is no evidence that progesterone supplementation prolongs gestation in multiple gestations, preterm premature rupture of membranes, or women with a cerclage:

Twin pregnancy — A randomized trial including 661 healthy women with twin gestations compared outcomes of weekly intramuscular injections of 250 mg of 17-alpha-hydroxyprogesterone caproate or matching placebo, starting at 16 to 20 weeks of gestation and ending at 35 weeks [31]. Delivery or fetal death before 35 weeks occurred in 41.5 percent of pregnancies in the progesterone group and 37.3 percent of those in the placebo group (RR 1.1; 95% CI 0.9 to 1.3). Few adverse events occurred and the rate did not differ between the two groups.

In a second randomized trial (Study Of Progesterone for the Prevention of Preterm Birth In Twins [sTOPPIT]), 500 women with twin pregnancy were randomized to receive daily vaginal progesterone gel 90 mg or placebo gel for 10 weeks from 24 weeks of gestation [32]. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was similar for both groups: 24.7 percent (61/247; six intrauterine deaths) in the progesterone group and 19.4 percent (48/247; four intrauterine deaths) in the placebo group (OR 1.36, 95% CI 0.89-2.09). The rate of adverse events did not differ between the two groups.

A meta-analysis including these two trials and a smaller one (26 subjects) confirmed that progesterone does not prevent early preterm birth in twin gestation (pooled OR 1.16, 95% CI 0.89-1.51). A subsequent randomized trial including 240 twin pregnancies also did not show a benefit [33].

Triplet pregnancy — In a randomized trial, the rate of fetal loss or preterm birth less than 35 weeks was not significantly different between women with triplets assigned to receive 17-alpha-hydroxyprogesterone caproate (250 mg intramuscularly once per week) and those who received a placebo from 16 to 20 weeks of gestation [34].

Another placebo-controlled randomized trial of prophylactic 17-alpha-hydroxyprogesterone caproate supplementation in triplet pregnancy also found no benefit, as well as a possible increase in midtrimester pregnancy loss [35].

Preterm premature rupture of membranes — A placebo-controlled randomized trial found no evidence that weekly injection of 17-alpha-hydroxyprogesterone extended gestation in women with premature rupture of membranes at 20 to 30 weeks of gestation [36]. Whether women with a history of a prior preterm birth due to preterm premature rupture of membranes benefit from progesterone supplementation in a subsequent pregnancy is not known.

Women with a cerclage — It is not clear whether 17-alpha-hydroxyprogesterone caproate provides additional benefit to women with a cervical cerclage in place. In a secondary analysis of a randomized trial evaluating cerclage, women with a prior spontaneous preterm birth, short cervix (<25 mm), and a cerclage had the same frequency of delivery before 35 weeks as comparable women who did not receive progesterone supplementation [37].

Other — There is no information on use of progesterone supplementation in fFN positive women (asymptomatic or symptomatic).

Inhibition of acute preterm labor — Tocolytic therapy of an acute episode of idiopathic preterm labor often abolishes contractions temporarily, but does not remove the underlying stimulus that initiated the process of parturition or reverse parturitional changes in the uterus. The net effect is that tocolytics are unlikely to prolong pregnancy by weeks or months. However, delivery can often be delayed for at least 48 hours so that glucocorticoids given to the mother can achieve their maximum effect. (See "Inhibition of acute preterm labor".)

Diagnosis and treatment of asymptomatic bacteriuria — Pregnant women with asymptomatic bacteriuria should be treated with antibiotics to reduce the risk of preterm birth. A meta-analysis of 14 randomized trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria demonstrated that antibiotic treatment was effective in clearing asymptomatic bacteriuria (OR 0.07, 95% CI 0.05-0.10), reducing the incidence of pyelonephritis (OR 0.24, 95% CI 0.19-0.32), and reducing preterm delivery and delivery of low-birth-weight infants (OR 0.60, 95% CI 0.45-0.80) [38].

A first trimester urine culture should be performed on all pregnant women [39,40], and regular antenatal screening is recommended for women at high-risk of asymptomatic bacteriuria (eg, women with sickle cell trait, recurrent urinary tract infections, diabetes mellitus, underlying renal disease). Reliance on symptoms to prompt screening is inadequate because symptoms such as frequency and nocturia are often attributed to the state of pregnancy. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)

Smoking cessation — Cigarette smoking has a modest dose-dependent relationship with preterm birth [41-44]. This effect can be explained, in part, by increased rates of smoking-related complications of pregnancy, such as placental abruption, placenta previa, premature rupture of membranes, and intrauterine growth restriction. However, the association remains after adjustment is made for these possible confounding factors, suggesting there may be a direct effect of cigarette smoking on spontaneous preterm labor and delivery. (See "Smoking and pregnancy".)

Smoking cessation should always be encouraged for its general health benefits. It is likely that smokers who decrease or stop cigarette smoking will reduce their risk of preterm birth, but this has not been proven.

Avoidance of cocaine — In the United States, cocaine has been detected in approximately 60 percent of women in preterm labor who have positive toxicology tests [45]. Health care providers should attempt to identify maternal cocaine use, provide information on the maternal and fetal risks associated with using cocaine, and help patients to stop using this drug. It is likely that this will reduce their risk of preterm birth, but this has not been proven. (See "Substance use in pregnancy".)

Decrease the rate of multiple gestation from ART — Multiple births are six times more likely to be preterm than singleton births [46]. The incidence of multiple gestation (especially higher-order multiple pregnancies) has increased in the past two decades, largely due to the increasing availability and success of assisted reproduction techniques (ART).

Strategies to prevent multiple conceptions resulting from ART include a firm diagnosis of infertility before initiating ART, limiting the number of pre-embryos that are transferred in each ART cycle, and, as a last resort, the judicious use of multifetal pregnancy reduction. (See "Strategies to control the rate of high order multiple gestation".)

Cervical cerclage — There is some evidence that cerclage may prolong pregnancy in subgroups of women, such as those with a history of multiple painless second trimester fetal losses associated with gross cervical changes. The efficacy of cerclage for prolonging pregnancy in women with a shortened cervix has not been consistently demonstrated in randomized trials [47]; the optimum treatment of these women remains to be determined. These issues are discussed in detail separately. (See "Cervical insufficiency".)

Reduce occupational fatigue — We feel that a woman with an uncomplicated pregnancy who is employed where there are no greater potential hazards than those encountered in routine daily life may continue to work without interruption until the onset of labor. Nevertheless, the physical demands of the woman's job should be considered, especially in women at high risk of preterm delivery.

A meta-analysis of 21 studies including a total of 146,457 women identified a high cumulative work fatigue score as the strongest work-related risk factor for preterm birth (OR 1.63, 95% CI 1.33-1.98) [48]. The results of this analysis are summarized in the table (table 2). Similar findings were reported in a subsequent large European case-control study that noted employed women were at higher risk of preterm birth if they worked longer than 42 hours/week, stood more than six hours/day, or had low job satisfaction [49].

The effects of reducing occupational fatigue have not been evaluated in randomized trials. Maternity legislation in many European countries has regulated work schedules and working conditions for pregnant women; however, none of the European countries except France have experienced a reduction in preterm birth rates [50]. Nevertheless, paid maternity leave, guaranteed job protection, and regulation of hazardous working conditions remain desirable societal goals.

Nutritional intervention — Women with adequate nutrition and a normal body-mass index have better pregnancy outcomes than other women, which suggests that nutritional interventions may have a role in preventing preterm birth. Randomized trials have provided evidence that some dietary interventions increase the length of gestation, but the evidence is not conclusive and these supplements cannot be recommended at this time.

N-3 fatty acid supplements — Low consumption of n-3 fatty acids (eg, fish oil) has been associated with a higher rate of preterm birth [51]. N-3 fatty acid supplements may induce uterine quiescence by favoring production of noninflammatory cytokines and weak eicosanoids over production of proinflammatory cytokines and eicosanoids causing uterine contractions [52]. When this hypothesis was evaluated, however, dietary intervention did not significantly reduce the maternal or fetal blood concentration of a variety of biomarkers associated with inflammation [53]. The following randomized trials exemplify this area of research:

A meta-analysis of six randomized trials involving 2783 women compared pregnancy outcome after supplementation with fish oil (and other prostaglandin precursors) versus placebo/no treatment [54]. Women allocated to receive fish oil had a lower risk of giving birth before 34 weeks of gestation (RR 0.69, 95% CI 0.49-0.99; two trials, 860 women), but the proportion delivering before 37 completed weeks was similar for both groups. These results were largely due to one large multicenter trial (Fish Oil Trials In Pregnancy [FOTIP]) [55,56].
After this meta-analysis, a randomized trial including 852 women with a history of preterm birth found the combination of omega-3 fatty acid and progesterone supplements was no more effective than progesterone supplementation alone (spontaneous preterm birth rate <37 weeks in omega-3/progesterone group 32.9 percent versus 35.6 percent in placebo/progesterone group; RR 0.92, 95% CI 0.77-1.11) [57]. There were no significant differences in preterm birth <32 or 35 weeks either.
Supplementation with docosahexaenoic acid (n-3 long chain polyunsaturated fatty acid) increased gestation by a mean of six days in women who received it in fortified eggs from 24 to 28 weeks of gestation until parturition (133 mg in fortified eggs versus 33 mg in unfortified eggs) [58].

Fish consumption — The effect of fish oil supplements on preterm birth has been studied in randomized trials and no benefit was found, as discussed above. The effect of fish consumption of length of gestation has only been evaluated in observational studies, which have reported discordant results [51,59-64]. In these studies, the benefits of fish consumption may be confounded by socioeconomic class, avoidance of more harmful foods that fish replaces, beneficial effects of nutrients in fish other than n-3 fatty acids, and/or other attributes that are discordant between fish consumers and nonconsumers. Two representative studies are illustrated below:

The Cardiovascular Risk Reduction Diet in Pregnancy (CARRDIP) trial reported a diet low in saturated fat and cholesterol and enriched with polyunsaturated fatty acids (fish, low-fat meats and dairy products, oils, whole grains, fruits, vegetables, legumes) markedly reduced the rate of preterm birth in low-risk pregnancies compared with controls consuming their usual diet (preterm birth 1/141 versus 11/149; mean gestational age at delivery 281 versus 277 days) [59].
In contrast, a prospective observational cohort study including 2109 pregnant women examined the association between seafood intake and length of gestation and preterm delivery and reported seafood intake was not associated with length of gestation or risk of preterm birth after adjustment for maternal and child factors [62].

Under-nutrition — There is some evidence supporting the hypothesis that maternal under-nutrition in pregnancy results in preterm birth [65]. In sheep, moderate maternal undernutrition around the time of conception results in accelerated maturation of the fetal hypothalamic-pituitary-adrenal axis, a precocious fetal cortisol surge, and preterm birth [66,67]. In Gambian women, pregnancies conceived during the rainy season when food is scarce were significantly shorter than those conceived when food was more plentiful [68]. Observations of shorter gestational length with early pregnancy exposure to the Dutch famine also support this hypothesis [69]. Thus, focusing on dietary events around the time of conception may be important in prevention of some cases of preterm birth.

Systematic reviews have found that neither isocaloric protein supplements [70] nor balanced protein/energy supplements [71] reduce the rate of preterm delivery. Most studies show that vitamin supplements during pregnancy do not reduce the risk of preterm birth [72-77], although they have other benefits. There may be potential benefits of micronutrient supplementation in specific subpopulations of pregnant women, such as those who are undernourished or HIV infected [78]; this topic is discussed in more detail separately. (See "Nutrition in pregnancy", section on 'Dietary components'.)

Avoiding a short interpregnancy interval — The highest risk of preterm birth appears to be in women with an interpregnancy interval of less than six months. (See "Interpregnancy interval and pregnancy outcome".)

UNPROVEN INTERVENTIONS

Diagnosis and treatment of genital tract infection — Lower genital tract infection has been associated with preterm delivery [79-85]. Such infection may serve as a marker of upper genital tract infection or may lead to direct migration of organisms to the decidua, fetal membranes, and amniotic fluid. Nevertheless, most studies have not shown a reduction in preterm birth after treatment of asymptomatic vaginal or cervical infection.

Evidence against the effectiveness of screening for and treating asymptomatic lower genital tract infection is summarized below by organism:

Chlamydia and gonorrhea — There is no evidence that treatment of chlamydia or gonorrhea prolongs gestation. The only controlled trial that evaluated the effect of treatment of chlamydia on gestational duration did not show a reduction in preterm birth [86]. However, screening for and treatment of these infections is recommended to prevent other maternal and neonatal sequelae. (See "Genital Chlamydia trachomatis infections in women" and "Diagnosis of gonococcal infections" and "Treatment of urogenital gonococcal infections".)
Bacterial vaginosis, Ureaplasma, group B streptococcus (GBS) — Prospective controlled trials and meta-analyses have reported either a modest or no effect of antibiotic treatment on prolonging gestation in asymptomatic women who screened positive for bacterial vaginosis [87-91], Ureaplasma urealyticum [92,93], or GBS [94], although these studies are undoubtedly confounded by recolonization or reinfection after therapy and intercurrent use of nonprotocol antibiotics. GBS screening in late pregnancy and chemoprophylaxis for prevention of early onset neonatal GBS infection is recommended. (See "Chemoprophylaxis for the prevention of neonatal group B streptococcal disease".)

Women with bacterial vaginosis and a previous preterm birth may benefit from bacterial vaginosis screening and treatment, but there are insufficient data to recommend this as a routine practice. This subject is discussed in detail separately. (See "Bacterial vaginosis", section on 'Treatment in pregnancy'.)

Trichomonas — Treatment of asymptomatic Trichomonas infection is not recommended during pregnancy because it does not prevent, and may even increase, the risk of preterm delivery [95]. In one large trial, 617 women with culture proven asymptomatic infection at 16 to 23 weeks of gestation were randomly assigned to receive either two doses of metronidazole (2 g) or placebo 48 hours apart [95]. All women were retreated with the same regimen at 24 to 29 weeks of gestation. Trichomonas resolved in 93 percent of metronidazole treated women and 35 percent of the placebo group. The rate of preterm birth was higher in treated than control women (19 versus 11 percent, relative risk 1.8; 95% CI 1.2-2.7), primarily related to an increased frequency of spontaneous preterm labor (10.2 versus 3.5 percent, relative risk 3.0; 95% CI 1.5- 5.9). This outcome was unexpected. The authors commented that the regimen of metronidazole administered was not a standard one and speculated that other bacteria may have increased in density during metronidazole treatment. Since extensive culturing was not performed, the presence of other infections was not determined. (See "Diagnostic approach to women with vaginal discharge or vulvovaginal symptoms", section on 'Vaginal culture'.)
Positive gram stain of vaginal smear — One exception to these negative studies was a multicenter trial in which all pregnant women presenting for a routine prenatal visit at 15 to 19 weeks of gestation were screened for bacterial vaginosis, vaginal candidiasis, and T. vaginalis by Gram stain of a vaginal smear [96]. The women were then randomly assigned to an intervention group (Gram stain results provided to care-giver and positive results treated with appropriate antibiotics) or a control group (Gram stain results not released to care-giver, usual care). Women in the intervention group had a significantly lower rate of spontaneous preterm birth than controls (3 versus 5 percent). This is surprising since over 70 percent of preterm births occurred in women with normal Gram stains. Given the low overall rate of preterm birth in this study, it is not clear whether such findings can be extrapolated to other populations.

The results of this trial need to be confirmed before any practice changes can be recommended. Of particular concern, other trials that randomly assigned women at high risk of preterm birth to antibiotic therapy or no antibiotic therapy found that antibiotic therapy had no, or a deleterious, effect (see 'Antibiotics' below).

Treatment of periodontal disease — The effect of treatment of periodontal disease on preterm birth is unclear, given discordant results among randomized controlled trials.

A meta-analysis of seven randomized trials on the effect of periodontal disease treatment on preterm birth found a benefit [97]. Using a random effects model, treatment of periodontal disease during pregnancy resulted in a significant reduction of preterm birth (OR 0.55, 95% CI 0.35-0.86) and a strong trend in reduction of low birthweight infants (OR 0.48, 95% CI 0.23-1.00). However, we are not convinced that this analysis proves that treatment of periodontal disease reduces the risk of preterm birth, given that the unadjusted data showed no effect, there was no effort to address the important issue of publication bias, and there was moderate heterogeneity among the trials. The available trials used varying criteria to diagnose periodontal disease and to define adverse outcomes. Moreover, they generally did not adequately adjust for confounders or have adequate sample size to detect significant differences in pregnancy outcomes.

After publication of this meta-analysis, results of the Maternal Oral Therapy to Reduce Obstetric Risk Study were published and showed that periodontal therapy did not reduce the incidence of preterm delivery before 37, 35, or 32 weeks of gestation, weight for gestational age, or neonatal morbidity [98]. This is the largest randomized controlled trial of the effects of maternal periodontal disease treatment on preterm birth rates; over 1800 pregnant women with periodontal disease were randomly assigned to receive treatment before 24 weeks of gestation or postpartum. Treatment consisted of up to four sessions of supra- and sub-gingival scaling and root planing using hand and ultrasonic instruments, full mouth tooth polishing, and oral hygiene instruction. Two subsequent large randomized trials of pregnant women with periodontal disease had a similar design and also found that treatment did not result in a significant improvement in any pregnancy outcome [99,100]. One of these, the Periodontal Infections and Prematurity Study (PIPS) [100], found that treatment might increase the risk of indicated preterm birth; this requires further study.

Periodontal disease could cause preterm birth if pathogens or inflammatory cytokines from the mother's mouth enter her blood and are transported across the placenta to the fetal compartment. It is also possible that periodontal infection is not a direct cause of preterm birth, but rather a marker of individuals who exhibit an excessive local or systemic inflammatory response to bacteria [101-104]. Such individuals may also hyperrespond to vaginal bacteria with enhanced production of cytokines that lead to preterm labor or rupture of membranes. Even if there is a causal association, it is possible that treatment of periodontal disease during pregnancy is inadequate to prevent sequelae in the index pregnancy. Although controlled trials have shown that treatment in pregnancy significantly improved periodontal health in the treatment group, periodontal disease was not cured and many patients demonstrated progression of disease [98].

At this time, there are inadequate data in this area on which to base a conclusion or recommendation with respect to pregnancy complications resulting from periodontal disease [105-107]. Prospective studies are needed in both low and high risk populations. Nevertheless, good oral health is desirable and periodontal disease should be treated as a component of good dental hygiene [108]. (See "Complications, diagnosis, and treatment of odontogenic infections".)

Measurement of uterine activity — Although an increase in uterine activity is a prerequisite for labor, randomized trials have shown that self-measurement of the frequency of uterine contractions by self-palpation/detection of signs of labor or through use of a home uterine monitor does not lead to a reduction in the rate of preterm delivery [109-113]. Moreover, such an approach increases visits to the labor and delivery unit, increases obstetrical intervention, and increases the cost of antepartum care [109,114,115].

Bed rest and hospitalization — Bed rest is often recommended for women at increased risk for preterm birth [116]. While bed rest improves uteroplacental blood flow and can lead to a slight increase in birth weight, there is no evidence that it decreases the incidence of preterm delivery [117-119]. Although underpowered, the only randomized trial attempting to determine whether hospitalization of women with arrested preterm labor improved outcome found hospitalized women had similar outcomes to those discharged home [120]. Moreover, exercise does not appear to increase the risk of preterm birth in healthy women. (See "Recommendations for exercise during pregnancy and the postpartum period".)

Abstinence — Coitus is not a risk factor for preterm birth; therefore, abstinence after pregnancy has been achieved has no role in strategies for prevention of preterm birth. (See "Risk factors for preterm labor and delivery".)

Prophylactic tocolytic drugs — The only randomized trial of prophylactic tocolytic therapy for prevention of preterm birth did not show a benefit [121,122]. (See "Management of pregnant women after inhibition of acute preterm labor".)

By comparison, pharmacological therapy is the cornerstone of management for acute preterm labor. (See "Inhibition of acute preterm labor".)

Antibiotics

Randomized trials — Randomized trials have shown that broad spectrum antibiotic therapy administered to asymptomatic women (pregnant or nonpregnant) without known infection does not prevent preterm labor or birth, and may increase the risk [123-126]. Three representative trials are illustrated below:

Treatment during pregnancy (fFN positive subjects) — In one trial, 715 women at high risk for preterm birth because of positive fFN test results (but no contractions) were randomly assigned to receive either metronidazole (250 mg orally three times per day) plus erythromycin (250 mg orally four times per day) or placebo pills for 10 days [123]. There was no difference between groups in the rate of preterm birth before 37 weeks, less than 35 weeks, or less than 32 weeks of gestation. Moreover, women with a prior spontaneous preterm delivery who took antibiotics had a higher rate of repeat spontaneous preterm delivery at less than 37 weeks than those taking placebo (47 versus 24 percent).
Treatment between pregnancies — In another trial, 241 postpartum women who had a spontaneous preterm birth between 16 and 34 weeks of gestation were randomly assigned to receive a course of azithromycin (two doses of 1 g four days apart)/metronidazole (750 mg daily for one week) or placebo every four months until they became pregnant again [124,127]. Antibiotic treatment did not reduce the risk of preterm birth in the subsequent pregnancy, and may have increased the risk. However, the antibiotic regimen did prevent the acquisition and promoted the resolution, but not the eradication, of bacterial colonization [128].
HIV infected women — A third trial randomly assigned 2661 mostly HIV positive women to receive a course of antibiotics or placebo at 20 to 24 weeks of gestation and then again during labor [125]. The antibiotic regimen was metronidazole 250 mg plus erythromycin 250 mg three times daily for seven days antepartum and metronidazole 250 mg plus ampicillin 500 mg every four hours beginning at the onset of labor and continuing until delivery. Antibiotic therapy did not significantly reduce the incidence of preterm birth, low birth weight, or histologic chorioamnionitis.

Meta-analysis — A meta-analysis of 17 randomized trials including diverse groups of high risk women confirmed these findings [129]. This analysis involved 12 trials that identified women at risk by abnormal vaginal flora, three that selected women at risk based on a previous preterm birth, and two that recruited women with a positive fetal fibronectin test result. There was no significant association between antibiotic treatment and reduction in preterm birth regardless of the criteria used to assess risk, the antimicrobial drug administered, or gestational age at time of treatment (overall combined random effect for delivery at less than 37 weeks RR 1.03, 95% CI 0.86–1.24).

Antibiotic therapy is also not effective as an adjunct to tocolysis for prolongation of pregnancy in the setting of intact membranes. (See "Inhibition of acute preterm labor", section on 'Antibiotics'.)

This population is different from that with threatened preterm birth in the setting of preterm premature rupture of membranes, where broad-spectrum antibiotics significantly prolong latency and improve perinatal outcome. (See "Preterm premature rupture of membranes".)

Enhanced prenatal care — The absence of prenatal care has been consistently identified as a risk factor for preterm labor and delivery, but it is less clear whether this association is causal or a marker of other factors that contribute to preterm birth. Retrospective studies cannot be adequately controlled to adjust for these confounding factors, while prospective randomized trials (no prenatal care versus standard care) would be unethical. Therefore, the only well-designed studies on the effect of prenatal care on preterm birth compare standard to enhanced care (ie, some combination of patient education, case management, home visits, nutrition counseling, and extra prenatal visits and cervical examinations).

To investigate whether enhanced prenatal care can decrease the incidence of preterm birth, the March of Dimes Multicenter Prematurity Prevention Trial conducted a randomized, controlled trial of 2395 women at high-risk of preterm birth [111]. The women were randomly assigned to either standard of care or an enhanced care intervention (more frequent prenatal visits, improved patient education regarding symptoms and signs of preterm labor, and weekly pelvic examinations after 20 to 24 weeks of gestation). There was no significant difference between the two groups in spontaneous preterm delivery rates.

Regular prenatal care should be encouraged and improves perinatal outcome in women with underlying medical disorders (eg, diabetes, chronic hypertension, thyroid disease) or pregnancy-related conditions (eg, preeclampsia); however, the March of Dimes trial suggests enhanced care is unlikely to decrease the incidence of preterm birth.

Social support — Likewise, intervention trials that provided enhanced social support (defined as emotional support and tangible assistance) have not clearly shown a benefit in terms of gestational length [130-132]. In particular, the two largest randomized trials concluded a program of social support did not reduce the overall rate of preterm delivery or low birth weight [131,132]. One of the trials included over 6000 teenagers [131] and the other included over 2000 high risk Latin American women [132].

There are limited data on other interventions for reducing stress in pregnant women (eg, physical relaxation, meditation, assessment and referral for services), but definite effects on birth outcome have not been proven [133]

Thyroid hormone — In a single randomized trial of 115 pregnant euthyroid women with thyroid peroxidase antibodies, levothyroxine therapy significantly reduced the rate of preterm birth (RR 0.28; 95% CI 0.10-0.80) [134]. Before thyroid antibody assessment or treatment can be considered in euthyroid women with history of preterm birth, further study is needed to confirm these findings.

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Adreas · 10 Νοεμβρίου,2011

Management of pregnant women after inhibition of acute preterm labor

Authors

Steve Caritis, MD

Hyagriv N Simhan, MD, MSCR

Section Editor

Charles J Lockwood, MD

Deputy Editor

Vanessa A Barss, MD

Disclosures

Last literature review version 19.2:Μάϊος 2011 |This topic last updated:Μάρτιος 31, 2011 (More)

INTRODUCTION — The optimal management of pregnancies after resolution of the acute episode of preterm labor (PTL) is unknown; there are no large randomized trials assessing various management strategies on which to base recommendations. Management of women after treatment of idiopathic PTL will be discussed here. Evaluation and management of women with suspected PTL are reviewed separately. (See "Fetal fibronectin for prediction of preterm labor and delivery" and "Inhibition of acute preterm labor".)

INPATIENT VERSUS OUTPATIENT MANAGEMENT — The only randomized controlled trial designed to determine whether hospitalization of women with arrested PTL affected the proportion of deliveries ≥36 weeks compared to women discharged home did not find a benefit [1]. In this trial, 101 women with singleton gestations, intact membranes, mean cervical dilation approximately 2.7 cm, and a diagnosis of arrested PTL between 24 and 33 4/7ths weeks of gestation were randomly assigned to hospitalization until 34 weeks of gestation or discharged home upon completion of a dexamethasone course. Tocolytics were not used; contractions arrested with conservative management. The proportion of deliveries ≥36 weeks was similar in both groups (71 and 72 percent, respectively).

This trial has been criticized for being underpowered and for a lack of generalizability because labor inhibiting drugs were not used at the study institution [2]. Nevertheless, in the absence of any convincing data showing a benefit of prolonging hospitalization, we feel outpatient management is the best option for managing most women with arrested PTL. There are, however, reasonable indications for longer hospitalization in some women. These include advanced cervical dilation (eg, >4 cm with bulging membranes or >3 cm with a funic presentation and breech lie), recurrent heavy vaginal bleeding (particularly if there has been a drop in the patient's fibrinogen or platelet count), concern regarding fetal well being (eg, recurrent variable decelerations associated with a funic presentation), or long travel time from a care facility with an appropriate level of obstetric and neonatal services and/or absence of a companion (eg, 30 to 45 minutes).

FETAL FIBRONECTIN TESTING — There are no data supporting the use of fetal fibronectin testing to further stratify risk status of fFN positive women after an episode of acute PTL. We do not recommend fetal fibronectin testing in asymptomatic women who are stable after an episode of acute PTL whether or not they have had a previous fFN test. (See "Fetal fibronectin for prediction of preterm labor and delivery", section on 'Fetal fibronectin'.)

HOME UTERINE ACTIVITY MONITORING — Results from studies on home uterine monitoring have reported inconsistent results and many have had serious design flaws [3-5]. The few well-designed trials show that home uterine activity monitoring does not significantly decrease the frequency of preterm delivery [6-8]. Based on these trials, the American College of Obstetricians and Gyecologists and other expert organizations do not recommend the use of home uterine activity monitoring to monitor women at risk for PTL or recurrent PTL [9,10].

BED REST — There is no evidence from large, well-designed trials that proves bed rest is effective or not effective for prevention of spontaneous preterm birth [11,12]. Bed rest is known to promote loss of trabecular bone density, increase venous thromboembolism risk, produce musculoskeletal deconditioning, and place significant psychosocial strain on individuals and families [11,13-19]. Thus, based on a lack of efficacy in prematurity prevention, and known significant risks, we do not suggest bed rest for this indication.

EXERCISE — Most trials of exercise in pregnancy have excluded women at risk for PTL or who develop PTL during the trial; therefore, it is difficult to assess the effect of exercise on these women. A Cochrane review found that women who engaged in aerobic exercise had no clinically important shortening of gestation compared to those who reduced their level of exercise or did not exercise [20]. By comparison, a meta-analysis concluded that physically demanding work may be modestly associated with preterm birth (OR 1.22, 95% CI 1.16-1. 29) [21]. Based on these associations, we feel it is reasonable to suggest modification of activities in women who have had one or more episodes of PTL [21]. In particular, we suggest that patients avoid prolonged standing (more than eight hours in a work day or more than four continuous hours per shift) [22,23], as this activity has been associated with PTL in observational studies. (See "Risk factors for preterm labor and delivery", section on 'Physical activity and work' and "Anatomical and physiological changes of pregnancy and exercise", section on 'Premature labor'.)

SEXUAL ACTIVITY — There is no evidence from well-designed trials that sexual activity affects the risk of preterm birth or onset of labor [24]. In a classic observational series, data were analyzed from 26,886 pregnancies to determine whether coitus was involved in the genesis of amniotic-fluid infections [25]. The frequency of infection was 156 of 1000 births when mothers reported coitus once or more per week during the month before delivery, versus 117 of 1000 when no coitus was reported; this difference was not statistically significant. However, the percentage of infected infants who died was higher in women who reported recent coitus (11.0 versus 2.4 percent when there was no coitus). The frequencies of low Apgar scores, neonatal respiratory distress, and hyperbilirubinemia were also about doubled when mothers reported coitus. The coitus-associated effects were greater in preterm than in fullterm infants. The pregnancies in the study took place between 1959 and 1966, when national perinatal mortality rates were higher than they are now. Deaths from coitus-associated infections may be less frequent today.

Both prostaglandins in semen and orgasm can contribute to increases in myometrial activity [26,27]. For this reason, as well as the data above, it is reasonable to suggest avoidance of intercourse for women with an arrested episode of preterm labor.

MAINTENANCE TOCOLYSIS — The utility of administering a tocolytic agent after successful suppression of an acute episode of PTL is controversial [28-38]. Several randomized controlled trials have been reported; however, most are small and with study design limitations.

There are several rationales for considering maintenance tocolysis after successful arrest of the initial episode of PTL: (1) the underlying stimulus for labor may persist and cause a recurrence; (2) the myometrium, having experienced a recent episode of PTL, may be in a chemical state of preparedness and thus have a low threshold for recurrence; and (3) contractions may have a positive feedback on myometrial contractility and lead to further contractions. As an example, elevated endogenous prostaglandins are known to increase oxytocin receptor density [39]. The inhibition of contractions, therefore, may reduce prostaglandin production and oxytocin receptor up-regulation.

There have been at least 11 randomized trials in which maintenance tocolysis was compared to placebo or to no treatment after arrest of acute PTL in patients with intact membranes (table 1).

Nifedipine — In two randomized trials comparing nifedipine to placebo, women treated with nifedipine maintained pregnancy one to four days longer than women who received no therapy, but this difference was not statistically significant [30,38]. The trials were too small to detect anything but large differences (>35 percent) in efficacy.
Beta-agonists — The remaining nine trials evaluated beta-agonist therapy: one of the nine reported that beta-agonist therapy was superior to placebo for prolonging pregnancy and two reported this therapy reduced the risk of recurrent PTL. The sample sizes in these three trials were small, but the effect size was large, thus allowing for a statistical difference to be demonstrated.

On the other hand, four of the nine trials reported beta-agonist therapy was no better than placebo in prolonging pregnancy or preventing recurrent PTL. These four trials, however, are of limited value because the prevalence of preterm birth was low; therefore, a very large sample size would be needed to demonstrate whether drug therapy was superior to placebo. The trials were too small to exclude the possibility of clinically important differences in outcome.

The remaining trial also found no benefit of beta-agonist maintenance therapy over placebo in prolonging pregnancy [35]. Although the authors found a possible benefit in the subgroup of patients with PTL prior to 32 weeks of gestation, this analysis was performed post hoc and needs to be confirmed in a prospective, randomized trial. This may be because women with contractions recruited after 32 weeks gestation are having normal uncoordinated uterine contractions and cervical ripening and thus are often not at great risk of preterm delivery. Their inclusion in tocolysis trials limits the ability of the study to determine treatment efficacy.

A Cochrane review, which included 11 randomized trials comparing oral beta-mimetics with alternative therapies or placebo for maintenance therapy after threatened PTL, concluded there was no significant benefit to oral beta-mimetic therapy [40]. Outcomes evaluated included rate of NICU admission, preterm birth, perinatal mortality, and perinatal morbidity.

The US Food and Drug Administration concluded that the risk of serious adverse events from prolonged terbutaline therapy of preterm labor (beyond 48 to 72 hours) outweighs any potential benefit [41].
Magnesium sulfate — Oral magnesium is not well absorbed and causes diarrhea. Moreover, a Cochrane review concluded that oral magnesium sulfate did not appear to be effective for preventing preterm birth after threatened preterm labor, although data were limited [42]. Magnesium sulfate did not reduce preterm birth compared to placebo or alternative therapy.
Atosiban — Lastly, the only randomized trial comparing an oxytocin antagonist (atosiban) to placebo for maintenance therapy after an episode of PTL did not find that active therapy significantly reduced preterm birth before 28, 32, or 37 weeks of gestation [32]. This double blind multicenter trial included 513 patients.

In summary, data from poorly designed studies do not support the use of maintenance labor inhibition for prevention of preterm birth. (See "Inhibition of acute preterm labor".)

PROGESTERONE SUPPLEMENTATION — There are some data suggesting progesterone supplementation is effective for prolonging latency in women with PTL during the current pregnancy [43,44]. Current clinical evidence does not support prescribing supplemental progesterone alone or as an adjunct to labor inhibition therapy for women with acute preterm labor. However, women who are already receiving supplemental progesterone for prevention of preterm birth because of a history of prior preterm birth may continue to receive the supplemental progesterone after an episode of PTL. (See "Prevention of spontaneous preterm birth", section on 'Supplemental progesterone'.)

REPEATED COURSES OF ANTENATAL GLUCOCORTICOIDS — A course of antenatal glucocorticoids is given to women at risk for preterm birth to reduce neonatal morbidity and mortality if preterm delivery occurs, these drugs do not prevent PTL or preterm birth. We do not recommend routine weekly courses of antenatal glucocorticoid therapy. This topic is discussed in detail separately. (See "Antenatal use of corticosteroids in women at risk for preterm delivery", section on 'Repeated courses of therapy'.)

ANTIBIOTICS — There is no proven benefit to use of prophylactic broad-spectrum antibiotics to delay delivery in the setting of PTL with intact membranes. A systematic review and meta-analysis of trials of asymptomatic nonlaboring women at high risk of preterm birth randomly assigned to antibiotic therapy or placebo did not find a significant association between antibiotic treatment and reduction in preterm birth, irrespective of criteria used to assess risk, the antimicrobial agent administered, or gestational age at time of treatment (relative risk of delivery at less than 37 weeks with antibiotic treatment 1.03; 95% CI 0.86-1.24) [45].

Likewise, there is no benefit to GBS chemoprophylaxis (even if GBS recto-vaginal culture is positive) once the patient is no longer at imminent risk of preterm birth. (See "Chemoprophylaxis for the prevention of neonatal group B streptococcal disease", section on 'Approach to threatened preterm delivery'.)

FOLLOW-UP — Follow-up visits typically are scheduled on a weekly basis to review signs and symptoms of PTL and to evaluate whether there has been further cervical change. Typically, this evaluation is performed by digital examination and/or sterile speculum inspection of the cervix. This examination permits the detection of further cervical dilation or effacement in the setting of minimal to no symptoms. As an example, a woman whose cervix was noted to be 2 cm of dilation on hospital discharge who subsequently is noted to have a cervical exam consistent with 4 cm of dilation may warrant hospitalized observation in case of precipitous delivery.

After acute labor inhibition, we do not routinely recommend a specific strategy of NSTs or serial ultrasound examinations for fetal growth assessment unless there is a medical or obstetrical indication. Preterm labor alone is not an indication for antenatal fetal surveillance. (See "Overview of fetal assessment".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient information: Preterm labor")

SUMMARY AND RECOMMENDATIONS — There are no large, well-designed randomized trials on which to base management of women after an episode of preterm labor.

We suggest outpatient management for stable patients (Grade 2B). Advanced cervical dilatation, vaginal bleeding, nonreassuring fetal status, or a long travel time to a hospital with appropriate levels of obstetric and neonatal care services are signs of an unstable situation. (See 'Inpatient versus outpatient management' above.)
We suggest patients avoid prolonged standing, heavy lifting, and sexual intercourse (Grade 2C). (See 'Exercise' above and 'Sexual activity' above.)
Fetal fibronectin testing, home uterine activity monitoring, and maintenance tocolysis are not useful for follow-up assessment and management of women with an episode of arrested preterm labor. Supplemental progesterone may or may not be useful for prolonging latency; additional data confirming this benefit are needed before we can make a clinical recommendation for its routine use. (See 'Fetal fibronectin testing' above and 'Home uterine activity monitoring' above and 'Maintenance tocolysis' above and 'Progesterone supplementation' above.)
Specific patient instructions upon hospital discharge must be individualized based on the woman's distance from the hospital, the nature of her symptoms, and her gestational age. (See 'Follow-up' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

GRAPHICS

Maintenance tocolysis compared to placebo

Author Treatments Sample size Primary endpoint Conclusion CreasyRitodrine vs placebo55Time to recurrent PTLRitodrine significantly delayed time to recurrence and number of recurrencesBrownTerbutaline vs placebo46Days to deliveryTerbutaline significantly prolonged pregnancyHolleboomRitodrine vs placebo95Recurrent PTL during oral treatment (7d)Ritodrine significantly reduced recurrencesLewisTerbutaline vs placebo200Prolongation of pregnancy >7dTerbutaline significantly prolonged pregnancy in women recruited <32 weeks; otherwise, no benefitValenzuelaAtosiban vs placebo512Time to recurrent PTLAtosiban significantly delayed time to recurrent laborCarrNifedipine vs no nifedipine74Days until deliveryNo benefit with nifedipineParillaTerbutaline vs placebo55Days until deliveryNo benefit of terbutaline either in prolongation or number of recurrencesRustMag chloride vs terbutaline vs placebo205Days until deliveryNo benefit with either magnesium or terbutaline in pregnancy prolongationGuinnTerbutaline pump vs placebo52Days until deliveryNo benefit with terbutaline in prolongationHow Terbutaline vs no terbutaline 184 Re-admissionsNo benefit with terbutaline in re-admissions or pregnancy prolongation Days until deliveryLyellNifedipine vs placebo71Achievement of 37 weeks of gestationNo benefit with nifedipine

newbie G · 10 Νοεμβρίου,2011

@aantonios

Μπορείτε να μας εξηγήσετε τι σημαίνουν τα αρχικά ART και PTL;

Adreas · 10 Νοεμβρίου,2011

Οι ενδείξεις και οι δόσεις της προγεστερόνης έχουν υπογραμμιστεί μαυριστεί και με πλάγια γράμματα

Πάτησα ART στο uptodate και έβγαλε ότι είναι assisted reproduction: υποβοηθούμενη αναπαραγωγή

PTL: preterm labor πρόωρος τοκετός

newbie G · 11 Νοεμβρίου,2011

Οι ενδείξεις και οι δόσεις της προγεστερόνης έχουν υπογραμμιστεί μαυριστεί και με πλάγια γράμματα
Πάτησα ART στο uptodate και έβγαλε ότι είναι assisted reproduction: υποβοηθούμενη αναπαραγωγή

PTL: preterm labor πρόωρος τοκετός

Ωραια, ευχαριστώ.

Άρα να μείνουμε στο ότι....

"The vaginal gel and tablet are indicated for use in ART"

Για να μην σχηματίζονται λαθος εντυπώσεις. Για μένα είναι πολύ σημαντικό το ότι η χρήση κολπικού τζελ και κολπικών υποθέτων προγεστερόνης συνιστάται στην υποβοηθούμενη αναπαραγωγή. Άρα κάποιες φορές καλά κάνουν οι γυναικολόγοι και χορηγούν προγεστερόνη. Δεν είναι όλες οι περιπτώσεις ίδιες.

Adreas · 11 Νοεμβρίου,2011

Υποβοηθούμενη αναπαραγωγή: τεχνητή γονιμοποίηση είναι αν δεν καταλάβατε, παιδιά του σωλήνα που έλεγαν παλιά

Adreas · 11 Νοεμβρίου,2011

Εγω νομίζω ότι πρέπει να παίρνουμε ότι μας λένε γιατροί είναι και ξέρουν σίγουρα κάτι παραπάνω άπο εμάς.μην τα ισοπεδώνουμε όλα ακόμα κ την ιατρική.

Η απάντησή μου είναι το θέμα αυτό:

http://parents.org.gr/forum/showthread.php?t=104546&page=2

AthinaP · 12 Νοεμβρίου,2011

Όταν σε μια εγκυμοσύνη αρχίζει το αίμα, είναι δύσκολο να φανεί σε ποια κατηγορία είναι οι εγκυμοσύνη:

Είτε είναι μια εγκυμοσύνη που πρόκειται να αποβληθεί, ό,τι και να δοκιμάσει ή να μη δοκιμάσει κανείς. Μπορεί να οφείλεται σε χρωμοσωμική ανωμαλία ή σε κάποιο άλλο λόγο που δεν θα γίνει γνωστός ποτέ. Πιστεύω, ότι ήσασταν σε αυτή την περίπτωση. Προφανώς, δεν βοήθησε η προγεστερόνη, δεν θα είχε βοηθήσει να μην πάρετε προγεστερόνη...

Μπορεί η εγκυμοσύνη να είναι σε μια κατηγορία που θα πάει τελικά καλά, άσχετα με το τι θα κάνει ή δεν θα κάνει κανείς. Υπάρχουν γυναίκες που μπέρδεψαν το αίμα με περίοδο και συνέχισαν κανονικά τις δραστηριότητές τους και κατάλαβαν την εγκυμοσύνη αρκετά μετά. Στο μεταξύ η εγκυμοσύνη προχωρούσε κανονικά.

Μπορεί τέλος, η εγκυμοσύνη να είναι σε μια γκρίζα περιοχή, που κάτι μπορεί να γίνει για να τη βοηθήσει. Είτε να τη βοηθήσει η προγεστερόνη (έχοντας η γυναίκα κάποια έλλειψη ήδη είτε απλά γενικώς), μπορεί να βοηθήσει η ακινησία. Στη δική μου εγκυμοσύνη με τα δίδυμα φάνηκε ότι μας βοήθησε η ξάπλα. Αντικειμενικά, στο αίμα η προγεστερόνη δεν έκανε τίποτα (φυσικά δεν ισχύει αυτό για όλες τις γυναίκες), αλλά κάθε φορά που σταματούσε το αίμα για 2-3 μέρες και ξανασηκωνόμουν, ξανάρχιζε πάλι. Οι πιο πολλές γυναίκες δεν μπορούν να πουν με σιγουριά αν και κατά πόσο τις βοήθησε ή δεν τις βοήθησε κάτι. Μπορουν να πουν, πήρα/δεν πήρα προγεστερόνη και έκανα παιδί, έμεινα αυστηρά/λιγότερο αυστηρά ξάπλα και έκανα παιδί, αλλά δεν μπορεί να εκτιμήσει κανείς με ακρίβεια ποια είναι αυτά τα ποσοστά.

Τέλος πάντων, απο τη στιγμή που μια γυναίκα έχει αίμα, είναι δύσκολο να εκτιμήσει σε ποια από τις παραπάνω κατηγορίες ανήκει. Και κάθε εγκυμοσύνη είναι διαφορετική. Υπάρχουν πράγματι κάποιες γυναίκες με επαναλαμβανόμενες αποβολές και αξίζει να διερευνηθούν όλοι οι γνωστοί σήμερα λόγοι για αποβολές (πιστεύω ότι δεν τους ξέρουμε ακόμα όλους). Πάντως οι περισσότερες από αυτές τις γυναίκες κάνουν τελικά παιδάκι.

Η προσωπική μου εμπειρία ήταν ότι το καλύτερο που έκανα για την κύηση ήταν που περάσαμε τις πρώτες μέρες στο κρεβάτι και δεν σηκώθηκα ούτε για γιατρό, ούτε για υπέρηχο... Και ο γιατρός μου αυτό με συμβούλεψε. Κάποιες εξετάσεις αίματος που έπρεπε να κάνω, ήρθε ειδικό άτομο σπίτι και πήρε το αίμα για τις εξετάσεις. Όταν είδαμε ότι συνέχιζε να στάζει το αίμα και κάπως είχε σταθεροποιηθεί η κατάσταση, τότε πήγα και στο γυναικολόγο. Σε κανένα χρονικό σημείο δεν υπήρχε μεγάλη ροή που να έδειχνε αποβολή. Μετά από αρκετές μέρες πήγα για τον πρώτο υπέρηχο και με πολλή προσοχή και καθόλου περπάτημα. Το αίμα κράτησε τελικά όλο το πρώτο τρίμηνο. Τα συμπτώματα εγκυμοσύνης, χωρίς φαρμακευτική προγεστερόνη ήταν ήδη πάρα πολύ έντονα και έγιναν εντελώς χάλια με την προγεστερόνη. Στην περίπτωσή μου υπήρχαν (πριν εμφανιστεί το αίμα) και αποτελέσματα εργαστηρίου πάνω από τα ανώτερα φυσιολογικά όρια καθώς και υπέρηχος, με ένα τεράστιο ωχρό σωμάτιο. Τίποτα δεν έδειχνε ότι η προγεστερόνη θα είχε κάποιο όφελος, αλλά μιλάω μόνο για μια προσωπική περίπτωση. Σε πολλές άλλες έχει αποδειχτεί στατιστικά ότι κάποιο όφελος μπορεί να έβγαινε.

Επίσης, υπάρχουν θεωρίες που είναι κατά του κολπικού υπερήχου όταν υπάρχει αίμα, ή ρήξη του σάκου σε πιο προχωρημένη κύηση (μου έτυχε και αυτό) γιατί μπορεί να εισάγει μικρόβιο. Αυτό είδα ότι αρκετοί γιατροί το αγνοούν. Τουλάχιστον έδινα σημασία στην προσωπική υγιεινή πριν την επισκεψη στο γιατρό.

Εννοείται ότι στην υποβοηθούμενη αναπαραγωγή χρησιμοποιείται η προγεστερόνη, καθώς ο οργανισμός της γυναίκας από μόνος του δεν είναι σε φυσική εγκυμοσύνη με τις αναμενόμενες ορμονες της εγκυμοσύνης. Οπότε κάποια φάρμακα δίνονται πρόσθετα, για να κάνουν προσομοίωση αυτού που θα συνέβαινε στον οργανισμό σε μια φυσικη εγκυμοσύνη. Θα υπήρχε ένα ωχρό σωμάτιο που θα παρήγαγε φυσική προγεστερόνη. Στην υποβοηθούμενη αναπαραγωγή, αυτό δεν υπάρχει φυσικά.

newbie G · 12 Νοεμβρίου,2011

Υποβοηθούμενη αναπαραγωγή: τεχνητή γονιμοποίηση είναι αν δεν καταλάβατε, παιδιά του σωλήνα που έλεγαν παλιά

Μια χαρά κατάλαβα. Για εξωσωματική μιλάμε κι εγώ ανήκω σ' αυτήν την κατηγορία.

Adreas · 13 Νοεμβρίου,2011

Πάντως με όλα που έψαξα, η συνταγογράφηση προγεστερόνης δεν έχει ένδειξη παρά μόνο στην εξωσωματική γονιμοποίηση.

Στις αιμορραγίες της εγκυμοσύνης δεν χορηγείται. Αμφισβητούμενα χορηγείται για τις γυναίκες με επαναλαμβανόμενες αποβολές καθώς και σε αυτές με ιστορικό πρόωρων τοκετών.

Όμως και εκεί που αμφισβητήσιμα που τη δίνουν είναι για μικρότερα διαστήματα. Μάλιστα η δόση είναι 1 ή 2 caps Utrogestan ημερησίως ενδοκολπικά (προσοχή οι παρενέργειες στο έμβρυο αναφέρονται σε αυτές τις δόσεις), ενώ στη χώρα μας είδα να χρησιμοποιούνται μέχρι δωδεκαπλάσιες δόσεις και μάλιστα από το στόμα και μάλιστα στο πρώτο τρίμηνο και για πολύ μεγαλύτερο χρόνο.

mmdad · 13 Νοεμβρίου,2011

Κανετε εκστρατια κατα της χρησης της προγεστερονης? Προσπαθητε να ενημερωθηται αν επρεπε να παρετε ή οχι? Ειστε γιατρος και ξερεται απο τον εαυτο σας αν εχουν παντα δικιο οι γιατροι ή οχι. Ζητησατε καποια ονοματα και σας δοθηκαν. Τι νοημα εχει συζυτηση? Και ποιον ενδιαφερει τελικα αν "εγω" πειρα ή δεν πειρα προγεστερονη???

Ευχομαι την επομενη φορα να πανε ολα καλα για σας και να κρατατε συντομα ενα μωρακι

Adreas · 13 Νοεμβρίου,2011

Έψαξα, έγραψα, αφιέρωσα πάρα πολλές ώρες. Για αυτό το συμπέρασμα το έγραψα για όσους δεν ξέρουν Αγγλικά.

Πολλοί με κατέκριναν όταν ζήτησα γιατρό που δεν χορηγεί προγεστερόνη, μου είπαν δεν είμαι καλός γιατρός, μου είπαν να πάω Αμερική ή Αγγλία να μείνω, εσείς μου είπατε ότι κάνω εκστρατεία…

Τι να κάνω, ήθελα να δείξω ότι είχα δίκιο.

Τώρα εσείς αφού σας αρέσει να παίρνετε προγεστερόνη, σε άλλους να δίνουν προγεστερόνη, εγώ πράγματι δεν έχω λόγο.

Ευχαριστώ τους ανθρώπους που με βοήθησαν με τις πληροφορίες τους για τα ονόματα και εύχομαι να το βρουν στο δρόμο τους το καλό!

SpirosT · 22 Αυγούστου,2012

Αγαπητοι φίλοι,

Διαβασα αυτο το ποστ σχετικα με την αναζητηση γυναικολογου που δε συνταγογραφει προγεστερονη, και μιας που βρεθηκαμε στην ιδια κατασταση (και εχουμε τα ιδια...μυαλα) με τον χρηστη aantonios, θα ηθελα πολυ να μοιραστειτε μαζι μου τα ονοματα γιατρων που ειχατε προτεινει στον χρηστη aantonios με PM.

Ειμαστε στις πρωτες 4-6 εβδομαδες της εγκυμοσυνης, και η συζυγος εχει παρουσιασει πολυ μικρες, καθημερινες ομως, αιμορραγιες. Ουσιαστικα δεν εχουμε γυναικολογο ακομα, και 2 γυναικολογοι που μας προταθηκαν απο γνωστους, κατοπιν τηλεφωνικης επικοινωνιας απλα μας εστειλαν για εξεταση β-χοριακης+προγεστερονης. Κατοπιν ληψης των αποτελεσματων (που ηταν εντος των φτ) μας συνεστησαν utrogestan (ο δευτερος συνεστησε και ενεσιμη IM προγεστ.). Ολη αυτη η διαδικασια εγινε μονο απο το τηλεφωνο (!), χωρις καμια εξεταση (!!), ουτε ληψη ιστορικου (!!!). Θεωρω απαραδεκτη την ασκηση ιατρικης με αυτον τον τροπο, γι'αυτο ψαχνω εναν αξιολογο γιατρο, ο οποιος δεν κανει του κεφαλιου του, ή οτι του λενε οι ιατρικοι επισκεπτες. Αν μπορειτε να μας βοηθησετε θα ημασταν ευγνωμονες!

Ευχαριστω!

Ευη@ · 23 Αυγούστου,2012

Eχεις δίκιο που δε συμφωνείς με την εξεταση-διαγνωση απο το τηλέφωνο,ούτε κι εγω.Σκέψου όμως πως μια μετακίνηση της εγκύου μπορεί να επιδεινώσει την κατάσταση καθως επίσης και πως ο διακολπικός υπέρηχος (μια και είναι τόσο λίγων εβδομάδων) επίσης δεν είναι οτι καλύτερο.Δυστυχώς για την χρήση των φαρμάκων στην εγκυμοσύνη δεν μπορούν να γίνουν σοβαρές έρευνες και είναι λογικό.Κανένας δε θα δεχότανε να πάρει φάρμακα για να δει αν πραγματικά θα βλάψουν ή θα βοηθήσουν το έμβρυο!!!Οσο αφορά την προγεστερόνη χωρίς να μπορώ να σου πω με βεβαιότητα οτι θα έχει θετικά αποτελέσματα είναι ίσως η μόνη που μπορεί να βοηθήσει διοτι διατηρεί σε καλή κατάσταση το ενδομήτριο.Πιστεύω πως σε μια τόσο μικρή εγκυμοσύνη αν έχει "αποφασιστεί" η αποβολή δε γίνεται τίποτα,εκτος κι αν η αιτία είναι το ενδομήτριο.Δε μου αρέσουν τα φάρμακα στην εγκυμοσύνη αλλά.....το ρισκάρεις?Μιλάμε για την γυναίκα και το παιδί σου.Μια λογική δόση δε θα προκαλέσει προβλήματα και να ξέρεις οι ορμόνες δεν παρουσιάζουν και την καλύτερη απορρόφηση σαν χημικες ουσίες.

Ευη@ · 23 Αυγούστου,2012

Το οτι ένας γιατρός προτείνει προγεστερόνη δεν είναι απαραίτητο να το κάνεις κιόλας.Εξηγήστε του τη θέση σας και θα το σεβαστεί.Πλήρη ακινησία και υπομονή!Σας εύχομαι ΟΛΑ να πάνε καλά!!

Cristy · 23 Αυγούστου,2012

Είχα κι εγώ τις ανησυχίες μου για την προγεστερόνη, τις οποίες και έχω εκφράσει σε προηγούμενα ποστ.

Τελικά είμαι έγκυος σε δίδυμα μετά από επιτυχημένη εξωσωματική στο κέντρο ΓΕΝΕΣΙΣ με γιατρό τον κο Πάντο.

Πήρα προγεστερόνη στη φάση προετοιμασίας του ενδομητρίου και στη φάση αναμονής των αποτελεσμάτων.

Με την πρώτη μέτρηση χοριακής και την τεράστια τιμέ της, έμεινα έκπληκτη όταν μου είπε ο γιατρός ότι οι δόσεις των λοιπών συμπληρωμάτων που παίρνω θα καθοριστούν και από τις τιμές προγεστερόνης και οιστραδιόλης.

Όντως, μέτραγα αυτές τις 3 τιμές (χοριακή - προγεστερόνη - οιστραδιόλη) ανά 3 μέρες για 5 φορές, όπου πάντα ήταν πάρα μα πάρα πολύ καλές.

Την προγεστερόνη μου την έκοψε ΑΜΕΣΩΣ και σταδιακά και τα οιστρογόνα.

Ειλικρινά, αισθάνομαι μεγάλη ευγνωμοσύνη. Βρήκα την όλη αντιμετώπιση πολύ πιο επαγγελματική από ότι περίμενα.

Και για τις εγκυούλες που έχουν "προβληματάκια" και θα επιθυμούσαν να μην μετακινηθούν, τα περισσότερα μικροβιολογικά με ένα τηλεφώνημα, στέλνουν άτομο για αιμοληψία στο σπίτι...

Adreas · 29 Οκτωβρίου,2012

Επειδή με ρωτούν με πμ και δεν μπαίνω συχνά

Σύμφωνα με όλα αυτά που δημοσίευσα: η προγεστερόνη-utrogestan σύμφωνα με τις οδηγίες της Αμερικής, που ισχύουν παγκοσμίως δεν έχει θέση σε απειλούμενη κύηση και αιμορραγίες.

Δίδεται σε μικρή δόση μόνο κατά την τεχνητή γονιμοποίηση στις αρχικές ημέρες. Επίσης δίδεται στο τέλος της κυήσεως, σε γυναίκες με ιστορικό πολλαπλών αποβολών στο τελευταίο τρίμηνο για ορισμένες μέρες πάλι.

Η δόση της είναι 1-2 κάψουλες ημερησίως κυρίως ενδοκολπικώς.

Οι μετέπειτα παρενέργειες της στο έμβρυο είναι αρρενοποίηση του θηλέως, θηλεοποίηση του αρρένος, και καρκίνος μαστού για τη μητέρα. Προσοχή στις προαναφερόμενες δόσεις και ενδείξεις. Σε πολλαπλάσιες δόσεις και χορήγηση σε όλα τα τρίμηνα δεν έχει μελετηθεί. Θα έπρεπε να γίνει μελέτη μόνο στην Ελλάδα, αφού είναι εξαίρεση.

Όλα τα παραπάνω δεν είναι δικά μου λόγια, αλλά αναφέρονται σαφέστατα στις δημοσιεύσεις που σας ανάρτησα. Οπότε αν έχετε αντιρρήσεις θα πρέπει να τις στείλετε στους καθηγητές πανεπιστημίου της Αμερικής που αναφέρονται στην αρχή μετά τον τίτλο. Το site είναι www.uptodate.com http://www.uptodate.com/home/contact-us και έχει τρόπο αποστολής μηνυμάτων και να πείτε ότι για τα συγκεκριμένα άρθρα και συγγραφείς κάνοντας αντιγραφή τίτλου και συγγραφείς

Γιατρούς που μου είπαν μέχρι τώρα εδώ στο φορουμ που δεν χρησιμοποιούν προγεστερόνη και μου ζητήθηκαν και αυτοί:

Δημήτρης Μπιλάλης

Βασ. Σοφίας 122

2107704393

http://www.venusmed.gr/el/content/gynaikologiko-iatreio-toy-maieytira-kai-gynaikologoy-dr-mixalis-s-lazanakis-kai-tis-maias-fi

TanKan · 16 Ιανουαρίου,2013

Πολλά συγχαρητήρια για το πολύ κατατοπιστικό φόρουμ!
1. Η σύζυγός μου είναι 40 ετών και θέλουμε να τεκνοποιήσουμε για πρώτη φορά. έμεινε έγκυος με την πρώτη προσπάθεια, αλλά στις 14 μέρες εγκυμοσύνης παρουσίασε αιμορραγία και ξεκινήσαμε 1 ένεση Lentogest υδροξυπρογεστερόνη 341 mg και χάπια Utrogestan 2 μαζί τρεις φορές την ημέρα για τρεις ημέρες. Η σύλληψη ήταν κακή και αποβλήθηκε τελικά πλήρως και ευτυχώς δεν χρειαστήκαμε απόξεση.

Όμως διάβασα ότι δεν κάνουν τίποτε για τις αιμορραγίες της κύησης. Επιπλέον δεν υπάρχουν στις αντίστοιχες περιπτώσεις στις οδηγίες της Αμερικής προς τους γυναικολόγους.

Από τώρα και έπειτα ο γυναικολόγος θέλει προληπτικά να λάβουμε Utrogestan από την στιγμή διαπίστωσης της εγκυμοσύνης!

Άρα πρέπει να βρω κάποιον γυναικολόγο που να μη χορηγεί Utrogestan στην περιοχή της Αθήνας ή Πειραιά. Ασφαλώς θέλω να τον πληρώνω κανονικά ως κανονικός ασθενής και όχι επειδή είμαι γιατρός να έχω ειδική αντιμετώπιση. Όπως δηλαδή ισχύει σε όλες τις χώρες, Αγγλία, Αμερική και Γερμανία που γνωρίζω από πρώτο χέρι.

2. Επίσης βλέπω ότι στο εξωτερικό η γέννα είναι δουλειά της Μαίας, εδώ έρχεται και ο γυναικολόγος. Όμως μόνο στην Ελλάδα κόβουν το περίνεο τη στιγμή της γέννας. Όπότε θα ήθελα ο γιατρός αυτός να μην κόβει την είσοδο του κόλπου προς τα κάτω. Δηλαδή να γίνουν τα πράγματα όπως γίνονται σε όλες τις χώρες εκτός της Ελλάδος.

3. Επίσης να μη βάζει ωκυτοκίνη για να γεννήσει γρήγορα η επίτοκος, αλλά να την περιμένει. Γιατί αν βάλεις ωκυτοκίνη τότε αν δεν πετύχει πας για καισαρική. Κανονικά στο εξωτερικό η μαία περιμένει την επίτοκο, 12 ώρες και συνήθως ξεγεννάει πάντα ξημερώματα. Αν κάτι πάει στραβά καλεί τον ιατρό. Βέβαια θα ήθελε η γυναίκα μου τον ιατρό παρόν, τη στιγμή που γεννά.

Άρα ψάχνω βασικά ιατρό να μη δίνει utrogestan και αν τα άλλα είναι δυνατό να μη γίνουν, καλό θα ήταν.

Σας ευχαριστώ εκ των προτέρων και περιμένω με αγωνία τις απαντήσεις σας

http://www.aalfafamily.com/ProgesteroneInPregnancy.html

http://www.naprotechnology.com/progesterone.htm

http://summaries.cochrane.org/CD005943/progestogen-for-treating-threatened-miscarriage

Υπάρχουν κι άλλες βιβλιογραφικές αναφορές. Βέβαια, η έρευνα είναι πάντα συνεχιζόμενη και προσφέρει πληροφορίες συνεχώς. Ας μην είμαστε απόλυτοι σε τίποτε.

Εάν δεν εμπιστευόμαστε το γιατρό μας, απλά επιλέγουμε άλλον. Η ιατρική επιστήμη στη χώρα μας είναι σε καλά επίπεδα. Δεν είμαστε Ουγκάντα. Δείτε σας παρακαλώ τη σχετική αναφορά: http://health.in.gr/news/scienceprogress/article/?aid=1231086186

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