CONTROLLED PREPARATION OF THE ENDOMETRIUM WITH EXOGENOUS ESTRADIOL AND PROGESTERONE - A NOVEL REGIMEN NOT USING A GONADOTROPIN-RELEASING-HORMONE AGONIST

In women having inactive ovaries, controlled preparation of the endometrium has been achieved with exogenous oestradiol and progesterone. We report on the feasibility and practicality of using a similar regimen for timing transfers of cryo-preserved embryos in women whose ovaries have not been suppressed. A total of 91 women having cryopreserved embryos from previous in-vitro fertilization (IVF) attempts received 4 mg/day of oestradiol valerate, starting on cycle day 1 of spontaneous (n = 85) or induced (n = 6) menstruation. A single blood sample was obtained on cycle day 14 for the measurement of plasma progesterone, oestradiol and luteinizing hormone (LH). Vaginal administration of micronized progesterone (300 mg/day) was started on day 15. Cryo-preserved embryos were transferred on day 17 or 18 provided that day 14 plasma progesterone remained less-than-or-equal-to 0.5 ng/ml, thereby confirming the absence of spontaneous ovulation prior to the administration of exogenous progesterone. Out of 91 cycles studied, plasma progesterone was found to be elevated (> 1 ng/ml) in only three (3.2%). Of the 88 scheduled transfers, 31 did not take place because no embryo survived thawing. In the remaining 57 cycles, 116 embryos were transferred resulting in 10 pregnancies, giving pregnancy and embryo implantation rates of 17.5 and 8.6% respectively. When a positive beta human chorionic gonadotrophin (HCG) titre was obtained, supplementation with oral oestradiol and vaginal progesterone was continued until placental autonomy was achieved. Of the 10 pregnancies, five (50%) were lost during the first trimester (biochemical, n = 1; miscarriage, n = 3; ectopic, n = 1). Because the supplementation regimen is similar to that used successfully in the egg donation programme, this unusually high incidence of first trimester pregnancy loss is believed to be coincidental. Yet it cannot be formally ruled out that the high miscarriage rate did not result from an inadequate preparation of the endometrium. When no transfer or no pregnancy occurred, resumption of menstrual cycles was prompt after oestradiol and progesterone treatment was discontinued on day 28. The value of this novel approach for timing transfers of cryopreserved embryos, involving the controlled preparation of the endometrium with oestradiol and progesterone, lies in its great clinical simplicity (only one hormonal sample) and practicality (2-week notice for scheduling transfers).