Endometrial biopsies showing inadequate development were observed after ovarian stimulation with the GnRH agonist Buserelin and HMG for IVF or GIFT when luteal supplementation was omitted. Ninety-one patients were randomly allocated to two luteal supplementation regimens: in 41 women HCG and in 50 women progesterone and oestradiol valerate. The pregnancy patients treated with a combination of the GnRH agonist and HMG a delay of implantation of 1.3 days was observed compared to pregnancies after clomiphene citrate-HMG stimulation. This delay was not due to slower preimplantation embryo development after GnRH agonist-HMG treatment. Temporarily defective function of the corpus luteum was evidenced by measuring serum progesterone, 17 beta-oestradiol and 17-hydroxyprogesterone in the patients receiving progesterone and oestradiol valerate. This inadequate corpus luteum function could be related to the prolonged blockage of pituitary gonadotrophic function after arrest of the GnRH agonist.

No abstract

To evaluate any beneficial effect of progesterone supplementation during the luteal phase of GIFT or IVF cycles stimulated by clomiphene citrate and HMG, two random prospective studies were performed. In the first study, a group of patients received a luteal phase supplement of 50 mg natural progesterone i.m. daily from the day of oocyte retrieval onwards. Initial results on 168 patients indicated that the pregnancy rate was similar in patients with or without progesterone supplements. No differences were found between the two groups in an analysis of pregnant and failed cycles. In a second study two different protocols of luteal phase supplementation after Buserelin-HMG stimulation were compared: natural progesterone in combination with oestradiol valerate (50 patients) or HCG supplements (41 patients). A 32% pregnancy rate per cycle was encountered in both groups. Endometrial biopsies, taken during the luteal phase from patients who did not undergo embryo replacement, revealed retarded endometrial development in most of the biopsies.

Luteal phases after in vitro fertilization (IVF) and embryo replacement have been studied in 241 cycles. A positive correlation was observed between the follicular estradiol (E2) peak and the progesterone (P) level on day 3 of the luteal phase, but no correlation was found between the E2-peak value and the luteal-phase duration or midluteal P concentration. When the trials were classified in relation to their outcome (i.e., clinical pregnancies, chemical pregnancies, or failures), the mean P level on day 3 of the luteal phase was significantly higher in clinical pregnancies than in chemical pregnancies and in failures. Mean E2 levels on day 3 were not significantly different among the three groups. Values of the E2/P ratio were significantly higher in chemical pregnancies than in the other groups. No significant differences were observed among the three groups on day 8. When comparing trials ending in failure to those leading to clinical pregnancy for the same patients, pregnancies were obtained in cycles in which early luteal P was higher and the early luteal E2/P ratio was lower than in failures cycles. These data suggest that high P levels and a low E2/P ratio in the early luteal phase might have a favorable influence on the implantation process in human IVF.

Groups of ovariectomized rats were taken as controls or given hormonal treatment mimicking the successive steps in the sequence of ovarian secretions leading to implantation. Total endometrium or separated epithelium and stroma were incubated in vitro with [35S]methionine. Dissolved proteins were submitted to two-dimensional polyacrylamide gel electrophoresis (pH range 5-7), followed by autoradiography. Priming with oestradiol (2 days) and subsequent treatment with progesterone (3 days) enhanced the synthesis of 12 and 14 polypeptides, respectively, which are specific for each of these treatments. Progesterone also suppressed the production of 10 oestrogen-dependent proteins both in the epithelium and the stroma. When an oestrogen-progesterone-oestrogen treatment was given, synthesis of all but 4 of the progesterone-induced polypeptides in the epithelium was inhibited while 5 of the proteins abolished by progesterone in this tissue compartment reappeared. These results are compatible with a mechanism of implantation acting at the epithelial level by lifting of intrauterine inhibition and stimulation by embryotrophic substances.