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Reviewing 780 in-vitro fertilization (IVF) cycles, where buserelin was commenced in the preceding luteal phase and human menopausal gonadotrophin on day 4 of the ensuing menses, 53 cycles were identified with sonolucent cysts (30-50 mm diameter). Of the latter 53 cycles, the serum oestradiol was significantly greater on day 4 in 22 cycles abandoned for poor follicular development than in 31 cycles which proceeded to oocyte retrieval (P less than 0.05). Of the 31 cycles proceeding to oocyte retrieval, nine had a day 4 serum oestradiol greater than 200 pmol/l (95th centile for day 4 oestradiol in patients without apparent cysts), and these cycles produced significantly fewer grade 1 embryos than the cycles with day 4 oestradiol levels less than or equal to 200 pmol/l (P less than 0.05). Six of the 53 cycles with cysts resulted in conception, and all of these cycles had a day 4 serum oestradiol less than 200 pmol/l. Among the 53 cycles with ovarian cysts, the serum progesterone on the day of abandonment in four cycles and on the day of human chorionic gonadotrophin administration in one non-abandoned cycle, was above the range established for 104 cycles without cysts. No significant difference was seen in day 4 serum androstenedione levels, and the day 4 serum progesterone was less than 5 nmol/l in all but one patient. Functional activity of ovarian cysts is associated with an adverse influence on IVF cycles.

Biochemical monitoring was undertaken in 22 treatment cycles for women with normal ovarian function who underwent pituitary suppression with buserelin and administration of exogenous oestradiol (E2) and progesterone (P) for cryopreserved embryo transfer (ET). Eighteen transfers of 1-4 thawed embryos, on the third day of exposure to progesterone, resulted in five clinical pregnancies (27.8%) and one biochemical pregnancy. There was no difference between pregnant and non-pregnant patients in the number and quality of embryos transferred, age, weight or infertility diagnosis. Serum E2 level from days 10-17 (the late proliferative phase) of the therapy cycle were significantly higher in the pregnant group compared with the non-pregnant group (P less than 0.05--P less than 0.005). There were no significant differences in P levels between the two groups from the onset of progesterone administration to the end of the cycle. However, as might be expected, the mean E2/P molar ratio in the pregnant group was significantly higher at the time of ET (P less than 0.02). It is concluded that biochemical monitoring during the embryo replacement cycle is necessary to tailor drug dosages for individual requirements to achieve adequate E2 levels before ET. Alternative routes of oestradiol administration need to be considered in patients with poor E2 profiles.

This study identifies a group of 87 patients, who demonstrated a 'poor' response to a standard buserelin/human menopausal gonadotrophin (HMG) regime. The subsequent outcome in 61 of these 'poor' responders when treated with a higher dose of HMG to achieve a satisfactory response was compared with 250 patients, who showed a 'good' response to the standard regime. 'Poor' responders were significantly older than 'good' responders (P less than 0.001), but no significant difference was demonstrated in the indication for in-vitro fertilization (IVF). Even on higher doses of HMG, 'poor' responders took longer for their follicles to achieve maturity than the 'good' responders (P less than 0.01). 'Poor' responders produced 8.9 oocytes per oocyte collection compared to 11.8 in the 'good' responders (P less than 0.01). The fertilization rate was significantly lower in the 'poor' responders compared to the 'good' responders (P less than 0.01). Although there was no significant difference in morphometric grading between 'poor' responder embryos and 'good' responder embryos, the rate of cell division was significantly slower in embryos of the 'poor' responders than the 'good' responders (P less than 0.01). The pregnancy rate per oocyte retrieval was 9% in the 'poor' responders compared to 29% in the 'good' responders (P less than 0.01). The implantation rate in the 'poor' responders was 4.4% compared to 16.1% in the 'good' responders (P less than 0.001).

The circulating levels of placental protein 14 (PP14) and progesterone were measured in three pregnancies resulting from the transfer of cryopreserved embryos. Two of these women had suppressed ovarian activity as a result of pituitary down-regulation with the luteinizing hormone-releasing hormone agonist (buserelin) prior to treatment with exogenous oestradiol and progesterone. After 14 days of oral oestradiol treatment and if the endometrial thickness was greater than 7 mm, progesterone was given intramuscularly for a further 14 days with embryo transfer on the third day of this treatment. On confirmation of pregnancy by human chorionic gonadotrophin analysis, progesterone administration was altered to transvaginal pessaries for maintenance of adequate progesterone levels and endometrial support. In the two women with ovarian suppression, PP14 levels remained below the 2.5th centile of the normal range for pregnancy. In the third pregnancy, embryo transfer was performed 3 days after a spontaneous luteinizing hormone surge in a normal menstrual cycle. In this pregnancy, PP14 levels were within the normal range. Ultrasonic examination confirmed three normal ongoing singleton pregnancies. These results suggest that the majority of PP14 production in normal pregnancy is under ovarian or anterior pituitary control and that the influence of progesterone is of a secondary nature.