Human Reproduction vol.7 no. 10 pp.1353-1356, 1992 Controlled preparation of the endometrium with exogenous oestradiol and progesterone: a novel regimen not using a gonadotrophin-releasing hormone agonist* Christophe Lelaidier 1 , Dominique de Ziegler, Jao Gaetano, Andre Hazout, Herv^ Fernandez and Rene* Frydman Department of Obstetrics and Gynaecology, H6pital A.Beclere, 157 rue de la Porte de Trivaux, 92141 Clamart, France 'To whom correspondence should be addressed 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 (TVF) attempts received 4 mg/day of oestradiol vakrate, 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 lutein- izing hormone (LH). Vaginal administration of mkronized 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 ^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 ft human chorionk gonadotrophin (HCG) titre was obtained, supplementation with oral oestradiol and vaginal progesterone was continued until placenta] 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 menstrua] cycles was prompt after oestradiol and progesterone treatment was discontinued on day 28. The value of this novel •Presented at the Society for Gynaecological Investigation (SGI) annual meeting in San Antonio, TX, USA, March 17-21. © Oxford University Press 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). Key words: endometrial receptivity/oestradiol valerate/ progesterone Introduction Timing transfers of cryopreserved embryos may be problematic for various practical reasons. In women having irregular menstrual cycles or luteal phase defect obvious problems occur, for which complicated solutions have been proposed. In women having regular menstrual cycles, identifying the pre-ovulatory luteinizing hormone (LH) surge by semi-quantitative urinary measurements may fail for purely technical reasons. This often leads to complicated evaluations of the hormonal profile around the presumed time of ovulation, which multiplies the number of blood samples and office visits and in turn results in a more expensive procedure. To date, two distinct alternatives to the natural menstrual cycle have been described for replacement of cryopreserved embryos: light ovulation induction (Mandelbaum et al, 1987), and endometrial priming with exogenous oestradiol and progesterone after suppression of the ovarian function by a gonadotrophin- releasing hormone agonist (GnRHa) (Schmidt et al., 1989; Meldrum et al., 1989; de Ziegler and Frydman, 1990). In search of a simpler method for timing transfers of cryopreserved embryos, we analysed the practicality and the efficacy of a different approach. This consisted of priming endometrial receptivity with oral oestradiol valerate and progesterone without inducing prior suppression of the ovarian function with a GnRH agonist. The rationale for this approach was that oestradiol treatment initiated on cycle day 1 would prevent follicular recruitment by interfering with the inter-cycle rise in plasma follicle stimulating hormone (FSH); consequently spontaneous ovulation would be avoided. In a preliminary study we looked at the hormonal profile and endometrial histology at the presumed time of implantation (de Ziegler et al., 1991). Plasma LH increased to surge levels in all six women studied but no follicular growth was noticed and no increase in plasma progesterone was triggered by the LH surges. Day 20 endometrium specimens showed normal secretory changes similar to previous findings made when oestradiol and progesterone cycles were administered to women permanently deprived of their ovarian function. Encouraged by the results of 1353