Micronized progesterone use for miscarriage: discussion questions of clinical trials

Ю. А. Дубоссарская, З. М. Дубоссарская

Abstract


Recurrent miscarriage is defined by two or more consecutive unsuccessful clinical pregnancies and occurs in 1–3% of couples. It is caused by a chromosomal abnormality, anatomical factors, including cervical incompetence, antiphospholipid syndrome and hereditary thrombophilia, immune, endocrine, and infectious causes.

The purpose of this review is to summarize published studies on the clinical aspects of the vaginal progesterone use in women with threatened miscarriage and recurrent miscarriage.

Indications for progesterone drugs use for the threatened abortion are: habitual miscarriage, luteal phase deficiency, pregnancy and infertility cured, which came as a result of assisted reproductive technology. It is intended that serum progesterone level is not a diagnostic criterion for evaluation of the luteal phase deficiency in connection with impulse hormone secretion.

A systematic review and meta-analysis of randomized controlled trials published in recent years comparing the use of vaginal progesterone to placebo or no treatment for the prevention of preterm birth and improve neonatal outcomes in singleton gestation and a short cervix. But the evidence is the progestogens use for the threatened miscarriage and recurrent miscarriage is still insufficient.

Results of a meta-analysis perfumed Wahabi H.A. et al. that united the 4 studies, have confirmed that progestogen is effective in the treatment of threatening miscarriage without an increase in the incidence of fetus congenital anomalies. However, data in this meta-analysis were combined various gestagens (progesterone, dydrogesterone), regardless of the dose, duration, and method of application.

Described the significant limitations of randomized placebo-controlled trial PROMISE, which do not adequately assess the potential reduction in risk of miscarriage during progesterone use.

Conducting a large randomized double-blind placebo-controlled multi-centre trial PRISM involving 4150 women for study progesterone effectiveness in reducing miscarriage rates in women with early pregnancy bleeding, the results of which are expected in 2018, gives hope to receive objective data.


Keywords


luteal phase insufficiency; threatened miscarriage; recurrent miscarriage; vaginal progesterone

References


Practice Committee of the American Society for Reproductive Medicine. “Evaluation and treatment of recurrent pregnancy loss: a committee opinion.” Fertil Steril 98.5 (2012): 1103–11. DOI: 10.1016/j.fertnstert.2012.06.048

Clinical protocol for obstetric care “Miscarriage”. Order of the Ministry of Health of Ukraine № 624 from 03.11.2008.

Van Niekerk, E.C., Siebert, I., Kruger, T.F. “An evidence-based approach to recurrent pregnancy loss.” South African Journal of Obstetrics and Gynaecology 19.3 (2013): 61–65.

Nybo Andersen, A.M. “Maternal age and fetal loss: Population based register linkage study.” BMJ 320.7251 (2000): 1708–12.

De la Rochebrochard, E., Thonneau, P. “Paternal age and maternal age are risk factors for miscarriage: Results of a multicentre European study.” Hum Reprod 17.6 (2002): 1649–56.

Stirrat, G.M. “Recurrent miscarriage.” Lancet 336.8716 (1990): 673–5.

Practice Committee of the American Society for Reproductive Medicine. “Current clinical irrelevance of luteal phase deficiency: a committee opinion.” Fertil Steril 103.4 (2015): 27–32.

Romero, R., Nicolaides, K.H., Conde-Agudelo, A., et al. “Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study.” Ultrasound Obstet Gynecol (2016). DOI: 10.1002/uog.15953

Carp, H.J. “Progestogens in the prevention of miscarriage.” Horm Mol Biol Clin Investig (2015). DOI: 10.1515/hmbci-2015-0058

Wahabi, H.A., Abed Althagafi, N.F., Elawad, M. “Progestogen for treating threatened miscarriage (Review).” Cochrane Database Syst Rev 12 (2011): CD005943. DOI: 10.1002/14651858.CD005943.pub4

Coomarasamy, A., Williams, H., Truchanowicz, E., et al. “A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.” N Engl J Med 373 (2015): 2141–8. DOI: 10.1056/NEJMoa1504927

Carpentier, P.A., Stanford, J.B., Boyle, P.C. “Progesterone in Women with Recurrent Miscarriages.” N Engl J Med 374 (2016): 894 DOI: 10.1056/NEJMc1600491

Haas, D.M., Ramsey, P.S. “Progestogen for preventing miscarriage.” Cochrane Database Syst Rev 10 (2013): CD003511. DOI: 10.1002/14651858.CD003511.pub3. Review.


GOST Style Citations


1. Practice Committee of the American Society for Reproductive Medicine. “Evaluation and treatment of recurrent pregnancy loss: a committee opinion.” Fertil Steril 98.5 (2012): 1103–11. DOI: 10.1016/j.fertnstert.2012.06.048

2. Клінічний протокол із акушерської допомоги «Невиношування вагітності». Наказ Міністерства охорони здоров’я України № 624 від 03.11.2008.

3. Van Niekerk, E.C., Siebert, I., Kruger, T.F. “An evidence-based approach to recurrent pregnancy loss.” South African Journal of Obstetrics and Gynaecology 19.3 (2013): 61–65.

4. Nybo Andersen, A.M. “Maternal age and fetal loss: Population based register linkage study.” BMJ 320.7251 (2000): 1708–12.

5. De la Rochebrochard, E., Thonneau, P. “Paternal age and maternal age are risk factors for miscarriage: Results of a multicentre European study.” Hum Reprod 17.6 (2002): 1649–56.

6. Stirrat, G.M. “Recurrent miscarriage.” Lancet 336.8716 (1990): 673–5.

7. Practice Committee of the American Society for Reproductive Medicine. “Current clinical irrelevance of luteal phase deficiency: a committee opinion.” Fertil Steril 103.4 (2015): 27–32.

8. Romero, R., Nicolaides, K.H., Conde-Agudelo, A., et al. “Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study.” Ultrasound Obstet Gynecol (2016). DOI: 10.1002/uog.15953

9. Carp, H.J. “Progestogens in the prevention of miscarriage.” Horm Mol Biol Clin Investig (2015). DOI: 10.1515/hmbci-2015-0058

10. Wahabi, H.A., Abed Althagafi, N.F., Elawad, M. “Progestogen for treating threatened miscarriage (Review).” Cochrane Database Syst Rev 12 (2011): CD005943. DOI: 10.1002/14651858.CD005943.pub4

11. Coomarasamy, A., Williams, H., Truchanowicz, E., et al. “A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.” N Engl J Med 373 (2015): 2141–8. DOI: 10.1056/NEJMoa1504927

12. Carpentier, P.A., Stanford, J.B., Boyle, P.C. “Progesterone in Women with Recurrent Miscarriages.” N Engl J Med 374 (2016): 894 DOI: 10.1056/NEJMc1600491

13. Haas, D.M., Ramsey, P.S. “Progestogen for preventing miscarriage.” Cochrane Database Syst Rev 10 (2013): CD003511. DOI: 10.1002/14651858.CD003511.pub3. Review. 





DOI: http://dx.doi.org/10.18370/2309-4117.2016.30.36-39

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ISSN 2411-1295 (Online), ISSN 2309-4117 (Print)