Endocrine Abstracts (2007) 14 P643

The clinical outcomes of stimulation of ovulation in patients with idiopathic hypogonadotropic hypogonadism (IHH) caused by mutations of GnRH receptor

Slawomir Wolczynski, Monika Zbucka & Katarzyna Jarzabek

Department of Reproduction and Gynecological Endocrinology, Medical University, Bialystok, Poland.

We report pregnancies obtained after stimulation by gonadotropins in 3 patients with IHH caused by homozygous or compound heterozygous mutations of GnRH receptor: (R139H/R262Q, R139C/ R139C, R139H/ Phe 308 del.);

Gonadotropin response to GnRH was observed in the first patient. All the patients were stimulated with gonadotrophins according to the protocole step up with the initial dose of 150IU FSH and 75 IU LH a day. The luteal phase was suported by hCG and progesterone. After 14 days of stimulation in the patient with R139H/R262Q mutated receptor, the estradiol concentration was 540 pg/ml and two mature follicles were observed. That patient was pregnant and gave birth. Patient with R139C/ R139C mutated receptor required higher doses and much longer stimulation, 225 IU FSH and 150 IU LH for 21 days. Compare to the estradiol concentration (620 pg/m) she developed three mature follicles and lot of small follicules. She conceived with triple pregnancies. The first trimester was complicated with OHHS. She miscarried at 22 weeks. In the second stimulation with the same doses for 21 days the estradiol concentration was 580 pg/ml, she was pregnant, the first trimester was also complicated with OHHS and she had twins.

The patient with R139H/ Phe 308 del required 225IU FSH and 150IU LH for 22 days and the estradiol concentration was 560 pg/ml and in the ovary three mature follicles and lots of small follicules was observed. She was pregnant,the first trimester was complicated with OHHS. Right now she is in 27 weeks of amenorrhea.

Conclusions: Patients with the mutations of GnRH receptor type loss off require much longer stimulation with higher doses comparing to IHH patients without GnRH receptor mutations. Despite low estradiol concentration the risk of OHSS and multiple pregnancy is high

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