enclomiphene and Infertility--Female

Enclomiphene, an isomeric component of clomiphene citrate, acts antagonistically to the oestradiol receptor at the hypothalamus level, inhibiting both negative and positive feedback, and resulting in the induction of ovarian stimulation and suppression of ovulation. The minimal ovarian stimulation protocol takes full advantage of these characteristics of clomiphene citrate. Administration of 50 mg clomiphene citrate is initiated on cycle day 3, and from day 8 patients receive 150 IU of FSH every other day. When the size of the dominant follicle and the oestradiol concentration reach the predefined values, gonadotrophin-releasing hormone agonist is administered to induce follicular maturation. Oocytes are then retrieved 32-35 h later. Because the short half-life of enclomiphene (24 h) is of critical importance in this protocol, it is necessary to continue oral administration of clomiphene citrate until the day before maturation is triggered. Of all 43,433 cycles initiated, the rates for oocyte retrieval and embryo cleavage were 83 and 64% respectively. The mean number of oocytes retrieved was 2.2. The rates for live births, miscarriages, and ectopic pregnancies, in relation to initiated cycles, including cases of frozen-thawed transfer, were 11.1, 3.4 and 0.2% respectively.

Topics: Adult; Clomiphene; Embryo Transfer; Enclomiphene; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Middle Aged; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Selective Estrogen Receptor Modulators

To determine the serum concentrations of enclomiphene and zuclomiphene across consecutive cycles of clomiphene citrate treatment in anovulatory infertile women.. Prospective cohort.. Tertiary institutional infertility clinic.. Fourteen consenting anovulatory infertile women receiving standardized, cyclic, incremental treatment with clomiphene citrate for ovulation induction.. Clomiphene citrate treatment (50-150 mg/d, cycle days 5-9), titrated to the minimum effective ovulation-inducing dose, was administered for three to six total cycles. Blood samples were obtained on cycle days 3 and 10 in each treatment cycle.. Serum concentrations of enclomiphene and zuclomiphene.. Cycle day 3 zuclomiphene levels were below assay limits in all initial cycles, increased progressively across three consecutive cycles, and thereafter plateaued. Cycle day 3 enclomiphene concentrations were uniformly undetectable. Cycle day 10 enclomiphene levels increased with dose administered, but these observations were not statistically significant.. Clomiphene citrate induction of ovulation results in an isomer-specific systemic accumulation of zuclomiphene across consecutive cycles of treatment. The combined maximum concentration of enclomiphene and zuclomiphene attained in practice approximates 100 nmol/L and is generally well below levels previously demonstrated to have adverse effects in vitro.

Topics: Adult; Anovulation; Clomiphene; Cohort Studies; Enclomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Ovulation Induction; Prospective Studies