P-789: Novel method of ovulation induction for the patients of so-called poor responders

Abstract

It is well known that there are some patients who cannot response properly by the exogenous administration of gonadotropin preparations. In addition, it is reported that plasma estrogen levels can modify the activities of gonadotropin receptors. Present study was performed to elucidate whether exogenous administration of estrogen preparation with Gn-RH agonist was effective to improve the response of gonadotropin administration in the patients of gonadotropin resistance syndrome. Open clinical trial under enough informed consents. Thirty-three patients who have resistance to gonadotropin therapy were subjected (35.4+/-3.2 years old). All of them had experiences of previous treatment of hMG (up to 600iu/day), and could not respond to the treatment (plasma estradiol levels, before: 15.3+/-5.1, after: 39.6+/-15.9 pg/ml). They were diagnosed as hyper-gonadotropic hypo-gonadismic state. Then, exogenous estrogen (conjugated equine estrogen: 1.25 - 2.5mg/day, or trans-dermal Estraderm M: 2-3 sheets/2days) was administered for 2 weeks with Gn-RH agonist (leuprorelin 1.88mg s.c.). After that, hMG preparation (Humegon 150iu/day) was administered to the subjects with estrogen preparations in gradual increasing method up to 600iu/day, and the follicular growths were observed by the transvaginal ultrasonic scanner. Then, 10000iu of hCG injection was performed when the matured follicles (diameter over 18mm) were observed, and the proper luteal support (administration of progesterone vaginal tablets, 60mg/day, for 2 weeks) was also done. Plasma FSH (before estrogen + Gn-RH agonist administration: 43.1+/-10.5, after: 7.3+/-3.1mIU/ml) and LH (before: 24.6+/-8.8, after: 5.8+/-2.6mIU/ml) decreased significantly by estrogen and Gn-RH agonist administration (p<0.001). Plasma estradiol levels increased up to 247.3+/-42.5 pg/ml after exogenous estrogen administration (p<0.001, compared to the levels before treatment). Twenty-seven cases out of 33 (total 102 cycles) could get mature follicles (over 18mm, 4.0+/-1.1 /case). Total dose of hMG preparation was 2375.6+/-239.0iu/case, and plasma estradiol level before hCG injection was 2220.5+/-472.2pg/ml. Twelve cases could get pregnancies (ten singletons and two twin) during this study. No severe side effect, such as ovarian hyper stimulation syndrome, was observed. It was suggested that gonadotropin receptors might be activated by the administration of exogenous estrogens, and the controlled ovarian stimulation using hMG with Gn-RH agonist after exogenous estrogen priming was effective for the treatment of the intractable ovulatory disturbances.