Evaluation of progestogen supplementation for luteal phase support in fresh in vitro fertilization cycles

Abstract

Objective: To evaluate the effectiveness of progestogen supplementation in improving clinical pregnancy rates in women undergoing fresh IVF cycles and to compare different routes, start times, durations and estrogen co-administration regimen.Design: Comprehensive systematic review and meta-analysis. Setting: University. Patients: Women undergoing fresh IVF cycles who did and did not receive progestogen supplementation. Intervention(s): Summary odds ratios (ORs) were calculated by binomial logistic regression. Main Outcome Measure(s): Clinical pregnancy rates. Results: 82 articles (26,726 women) were included. Clinical pregnancy rates were increased by intramuscular (OR=4.57; p<0.001), vaginal (OR=3.34; p<0.01), subcutaneous (OR=3.36; p<0.01) or oral (OR=2.57; p<0.05) progestogen supplementation versus no treatment. Greatest benefit was observed when progestogenswere supplemented intramuscularly versus vaginally (OR=1.37; p<0.001). The optimal time to commence administration was between oocyte retrieval and embryo transfer (OR=1.31; p<0.01), with oocyte retrieval +1 day being most beneficial. Co-administration of estrogen had no benefit (OR=1.33; p>0.05) whether progestogens were coadministered vaginally or intramuscularly. Clinical pregnancy rates were equivalent when progestogen supplementation was ceased after ≤3 weeks or continued for up to 12 weeks (OR=1.06; p>0.05). Conclusion:This broad-ranging meta-analysis highlights the need to re-evaluate current clinical practice. The use of progestogens in fresh IVF cycles is substantially beneficial to clinical pregnancy. Critically, the use of intramuscular progestogens should not be dismissed, as it yielded the greatest clinical pregnancy rates. Pregnancy success was impacted by initiation of therapy, with one day after oocyte retrieval being optimal. There is little evidence to support co-administration of estrogen or prolonging progestogen treatment beyond three weeks.

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats

“…A “uterine first-pass effect” that occurs when steroid hormones are delivered through the vagina has been suggested [ 27 ]. Vaginal administration of progesterone supplements in the luteal phase has been proven to have uterine effects that exceed the response that can be expected from the circulating levels of progesterone [ 28 , 29 ], with ~10-fold progesterone delivery to the uterus in ~7-fold lower circulating concentrations than intramuscular injections [ 30 , 31 ]. In our previous pilot study, we demonstrated that intermittent vaginal injection of rhFSH in women receiving IVF treatment resulted in proper folliculogenesis, fertilization rate, implantation rate, and pregnancy rates [ 32 , 33 ].…”

Luteal-phase support in assisted reproductive technology: An ongoing challenge

“…However, a systematic review suggested that the day after oocyte pick up is the best time for initiation of LPS and that continuing more than three wk does not improve clinical pregnancy rates (85). The ESHRE guidelines recommended that LPS should be started in the interval time between the evening of the day of ovum pick up and day 3 post oocyte retrieval (39).…”

Termination of pregnancy: what can we do for the prevention?

“…В пользу микронизированного прогестерона говорит еще один систематический обзор и метаанализ, включающий 82 статьи (26 726 пациенток) [25]. Установлено, что на благоприятный исход беременности повлияло назначение прогестерона с первого дня после получения ооцитов в программах ВРТ.…”