Endometrial preparation for egg donor recipients or for frozen embryo transfers

Couples undergo in vitro fertilisation (IVF) after a long period of subfertility, because women have blocked fallopian tubes or severe endometriosis, where the male partner has a reduced semen count, or when pregnancy has not resulted after previous less invasive fertility treatment. Subsequent to an unsuccessful fresh embryo IVF cycle, a frozen-thawed embryo transfer can be performed when frozen embryos are available. Alternatively for women who have:ovarian insufficiency (premature menopause), poor ovarian capacity to respond to stimulation, or or have had several unsuccessful IVF cycles, oocyte donation is a frequent treatment option, particularly for older women. Adequate hormonal preparation of the endometrium is of outmost importance in both egg donor and frozen embryo replacement cycles to provide the optimal chances of pregnancy. Many drugs and various modes of administration have been tried by several investigators in order to optimise implantation rates and consequently improve the success rates of the embryo transfer procedures. A total of 22 randomised controlled trials were included in this review. There is insufficient evidence from these trials to be able to identify one particular intervention for endometrial preparation that clearly improves the treatment outcome for women receiving embryo transfers with either frozen embryos or embryos derived from donated oocytes. Better quality studies are needed to more accurately evaluate each treatment.

Authors' conclusions: 

There is insufficient evidence to recommend any one particular protocol for endometrial preparation over another with regard to pregnancy rates after embryo transfers. These were either frozen embryos or embryos derived from donor oocytes. However, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation is commenced prior to oocyte retrieval in oocyte donation cycles. Adequately powered studies are needed to evaluate each treatment more accurately.

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Background: 

If a fresh embryo, assisted reproductive technology procedure cycle is unsuccessful and there are frozen embryos available, a frozen-thawed embryo transfer is performed. In some specific cases women may undergo oocyte donation treatment. In both situations the endometrium is primed by the administration of estrogen and progesterone. To prevent the possibility of spontaneous ovulation, gonadotropin-releasing hormone (GnRH) agonists are frequently used.

Objectives: 

To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate.

Search strategy: 

We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, and abstracts of reproductive societies' meetings (from inception). No language restrictions were applied. Experts in the field were contacted.

Selection criteria: 

Randomised controlled trials evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers.

Data collection and analysis: 

Two review authors independently applied the inclusion criteria, assessed trial risk of bias, and extracted data.

Main results: 

Twenty two randomised controlled trials were included. Five studies analysed the use of a GnRH agonist versus control. No significant benefit was demonstrated when using GnRH agonists. No evidence of statistically significant benefit was found for one GnRH agonist over another, or vaginal over intramuscular progesterone administration. No difference in pregnancy rate was demonstrated when no treatment was compared to aspirin, steroids, ovarian stimulation, or human chorionic gonadotropin (hCG) prior to embryo transfer, although using hCG several times before the oocyte retrieval decreases the pregnancy rate. Finally, when oocyte recipients were studied further, starting progesterone on the day of oocyte pick-up (OPU) or the day after OPU produced a significantly higher pregnancy rate (OR 1.87, 95% CI 1.13 to 3.08) than when recipients started progesterone the day prior to OPU.