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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).

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.

Human granulosa cells were prepared from follicular aspirates obtained during oocyte collection for in-vitro fertilization. Following several days in culture, cells were washed and then progesterone output was measured in 2-h incubations. After culture for 3 days, incubated cells responded well to human chorionic gonadotrophin (hCG) and prostaglandin (PG) E2with similar levels of maximum response. Exposure of cultured cells to epidermal growth factor (EGF) for 2 days (days 3–5) led to substantial increases both in basal production and in responses to hCG and PGE2during subsequent incubations. These effects of EGF were not accompanied by measurable increases in DNA levels in cultures over this time. Results may point to a possible paracrine role for EGF-like factors modulating the activity of cells forming the early corpus luteum.Journal of Endocrinology(1989) 121,397–402

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.

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 < 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 < 0.01). ‘Poor’ responders produced 8.9 oocytes per oocyte collection compared to 11.8 in the ‘good’ responders (P < 0.01). The fertilization rate was significantly lower in the ‘poor’ responders compared to the ‘good’ responders (P < 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 < 0.01). The pregnancy rate per oocyte retrieval was 9% in the ‘poor’ responders compared to 29% in the ‘good’ responders (P < 0.01). The implantation rate in the ‘poor’ responders was 4.4% compared to 16.1% in the ‘good’ responders (P < 0.001).