Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate

CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.

Endocrine changes after laparoscopic ovarian drilling in clomiphene citrate - resistant women with polycystic ovarian syndrome

To study the effects of laparoscopic ovarian drilling on the serum hormone levels in clomiphene citrate resistant women with polycystic ovarian syndrome [PCOS] and to determine the criteria which influenced their clinical response. A prospective study that was carried out at Salmaniya Medical Complex in Bahrain. One hundred and eighty-one women with clomiphene citrate-resistant PCOS were treated with laparoscopic ovarian drilling, all procedures were performed over a 4-year period between June 1996 and June 2000. Fasting blood samples for determination of the serum levels of luteinizing hormone [LH], follicle stimulating hormone [FSH], LH-FSH ratio, testosterone and prolactin were taken during the follicular phase before and one month after laparoscopic ovarian drilling. Responders who ovulated spontaneously after the drilling were obese and had higher preoperative LH levels and the LH-FSH ratio. Both responders and non-responders showed a significant decline in LH, LH-FSH ratio and testosterone with a significant increase in FSH but no significant change in prolactin mean values compared with pretreatment levels. The magnitude of change was significantly higher for LH and the LH-FSH ratio [p<0.05] in responders, while there were no significant differences in the corresponding values of the other hormones between the 2 groups. Moreover, the decrease in LH [p<0.01] and the LH-FSH ratio [p<0.05] was significantly greater in obese than non-obese women and this was only observed in the responders group. Laparoscopic ovarian drilling is an effective procedure in women with clomiphene citrate resistant PCOS. It produces significant endocrine changes with better results in obese patients with higher preoperative LH values and LH-FSH ratio. The magnitude of these changes was the highest in obese responders

A má resposta à estimulaçäo ovariana controlada com gonadotrofinas em fertilizaçäo in vitro / The low response to ovulation induction with gonadotropins for in vitro fertilization

Existe um grupo especial de pacientes dentro da fertilizaçäo assistida chamadas de más respondedoras, que apresentam uma resposta diminuída à estimulaçäo ovariana controlada com gonadotrofinas, juntamente com uma baixa taxa de gravidez nestes ciclos. Além do elevado custo financeiro, os resultados desapontadores provocam um desgaste físico e emocional acentuados. Neste trabalho os autores procuram definir esse grupo de pacientes de acordo com a literatura médica mundial, bem como expor os métodos para se tentar prever uma má resposta e as alternativas de tratamento para essas pacientes.