Luteal phase support for assisted reproduction cycles

• Published in: Cochrane database of systematic reviews 2015-07, Vol.2015 (7), p.CD009154
• Main Authors: van der Linden, Michelle, Buckingham, Karen, Farquhar, Cindy, Kremer, Jan A M, Metwally, Mostafa
• Format: Article
• Language: English
• Subjects: Chorionic Gonadotropin - adverse effects; Chorionic Gonadotropin - therapeutic use; Drug Therapy, Combination; Estrogens - therapeutic use; EVALUATION OF SUBFERTILITY TREATMENTS RELATING TO THE FEMALE PARTNER; Female; Gonadotropin-Releasing Hormone - agonists; Gynaecology; Humans; Live Birth - epidemiology; Luteal Phase - drug effects; Luteal Phase - physiology; Ovarian Hyperstimulation Syndrome - chemically induced; Pregnancy; Pregnancy Maintenance - drug effects; Progesterone - therapeutic use; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD009154.pub3

Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques(ART), progesterone and/or hCG levels are low, so the luteal phase is supported with progesterone, hCG or gonadotropin-releasing hormone (GnRH) agonists to improve implantation and pregnancy rates. To determine the relative effectiveness and safety of methods of luteal phase support provided to subfertile women undergoing assisted reproduction. We searched databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and trial registers. We conducted searches in November 2014, and further searches on 4 August 2015. Randomised controlled trials (RCTs) of luteal phase support using progesterone, hCG or GnRH agonist supplementation in ART cycles. Three review authors independently selected trials, extracted data and assessed risk of bias. We calculated odds ratios (ORs) and 95%confidence intervals (CIs) for each comparison and combined data when appropriate using a fixed-effect model. Our primary out come was live birth or ongoing pregnancy. The overall quality of the evidence was assessed using GRADE methods. Ninety-four women RCTs (26,198 women) were included. Most studies had unclear or high risk of bias in most domains. The main limitations in the evidence were poor reporting of study methods and imprecision due to small sample sizes.1. hCG vs placebo/no treatment (five RCTs, 746 women)There was no evidence of differences between groups in live birth or ongoing pregnancy (OR 1.67, 95% CI 0.90 to 3.12, three RCTs,527 women, I2 = 24%, very low-quality evidence, but I2 of 61% was found for the subgroup of ongoing pregnancy) with a random effects model. hCG increased the risk of ovarian hyperstimulation syndrome (OHSS) (1 RCT, OR 4.28, 95% CI 1.91 to 9.6, low quality evidence).2. Progesterone vs placebo/no treatment (eight RCTs, 875 women)Evidence suggests a higher rate of live birth or ongoing pregnancy in the progesterone group (OR 1.77, 95% CI 1.09 to 2.86, five RCTs, 642 women, I2 = 35%, very low-quality evidence). OHSS was not reported.3. Progesterone vs hCG regimens (16 RCTs, 2162 women)hCG regimens included comparisons of progesterone versus hCG and progesterone versus progest