ABSTRACT
Ovulation induction has been a major breakthrough in the management of female infertility since many decades. Letrozole, an aromatase inhibitor has been used as a potential therapy for ovulation induction. A large number of clinical evidences have been emerging which cite the beneficial role of Letrozole in conditions like anovulatory infertility, polycystic ovary syndrome (PCOS), unexplained infertility and an incipient role in endometriosis- related infertility with regards to higher live-birth rates. Letrozole is a superior alternative to Clomiphene citrate (CC) which has been used conventionally as ovulation inducer. Clomiphene citrate has certain well-defined disadvantages, whereas Letrozole overcomes these limitations to a reasonable extent. The peripheral anti-estrogenic effect of CC leads to prolonged depletion of estrogens receptors, adversely affecting endometrial growth and development as well as quantity and quality of cervical mucus. Persistent blockade of estrogen receptor leads to CC resistance and is associated with reduced ovulation and pregnancy rates. Available evidences suggest Letrozole is superior to CC owing to the lack of persistent anti-estrogenic action due to its short half- life and lack of action on estrogen receptors. This typically leads to monofollicular growth and also higher live birth rates. The current evidences suggest that Letrozole can be placed as first line therapy for the management of infertility due to PCOS and unexplained infertility.
ABSTRACT
Clomiphene citrate is the traditional first-line treatment for chronic anovulation that characterizes polycystic ovary syndrome (PCOS). A gold standard therapy has always been Clomiphene Citrate (CC). However, 20%-25% of PCOS women fail to ovulate with incremental doses of CC. A good body of evidence suggest that alternatives for PCOS women with CC-resistant anovulation include insulin sensitizers like metformin and pioglitazone. Insulin sensitizers improves pregnancy outcome and ovulation rate by and acts by ameliorating insulin sensitivity and hyperandrogenemia. Metformin is preferred in obese women. Gonadotropins induce ovulation and maintain optimal follicle growth via controlled administration of follicle stimulation hormone. Two regimens are used which includes high and low dose regimen. Low dose regimen is preferred but is associated adverse effects like ovarian hyperstimulation syndrome (OHSS) and increased cost. Extending clomiphene therapy reduces cost and improves pregnancy outcome. Glucocorticoids are preferably used when serum Dehydroepiandrosterone levels are > 200µg/dL. Bromocriptine improves ovulation rate by decreasing prolactin levels. Human Chorionic Gonadotropin restores ovulation but its use is limited during intrauterine insemination. Tamoxifen acts in a similar way as CC but has lesser antiestrogenic effect on the endometrium, cervical mucus, and granulosa cells, hence an added advantage of monofollicular ovulation. Aromatase inhibitors block conversion androstenedione and testosterone to estrogen in ovary and improves ovulation rate. Added advantage includes lesser cost, simple to use, no danger of multiple pregnancies and convenient for patient. Combination of GnRH analogues and Gonadotropins are associated with increased risk of OHSS. D-chiro-inositol, N-Acetylcysteine, melatonin and acarbose are tried with little success.
ABSTRACT
OBJECTIVE: The aim of this study was to evaluate the efficacy of metformin for ovualtion induction and pregnancy in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). METHODS: From March 2001 to March 2002, 19 patients with PCOS who had at least two consecutive cycles of anovulation in response to CC treatment up to 250 mg/day at the Infertility Center of Moon Hwa Hospital were enrolled in this study. The participants were required to have tubal patency on hysterosalpingography and their husbands were required to have normal semen analysis. The mean age was 30.5 +/- 3.6 years, the body weight 62.7 +/- 10.1 kg, the duration of infertility 3.7 +/- 2.1 years and the BMI 24.7 +/- 3.6 kg/m2. For 19 patients, a total of 75 cycles were treated with 1) CC+gonadotropin (group 1; 24 cycles), 2) CC+metformin (group 2; 29 cycles), or 3) CC+gonadotropin+metformin (group 3; 22 cycles). As for gonadotropin, highly purified-follicle stimulating hormone (HP-FSH) or/and hMG were used from the 3rd day of CC treatment. In the first cycle, metformin (1,500 mg/day) was administered during 1-28 days of menstrual cycle. Metformin was discontinued when a pregnancy was confirmed. RESULTS: Among 19 patients, 17 patients were ovulated (89.5%) and 7 patients (36.8%) were pregnant. Of a total of 75 cycles, 51 cycles (68.0%) were ovulated successfully with one of three treatment methods. Metformin treatment had similar ovulation rate compared to gonadotropin treatment. There was no significant difference in ovulation rate among the three groups (70.8% vs 58.6% vs 63.7%). However, the pregnancy rate was significantly higher in group 3 (18.2%, 4 cycles) compared to group 1 (8.3%, 2 cycles) and group 2 (6.9%, 2 cycles). Of pregnant cycles, all 2 cycles from group 1 were spontaneously aborted. One cycle in group 2 and one cycle in group 3 were spontaneously aborted and all other pregnant cycles were normally delivered. CONCLUSION: With the combination therapy of metformin, the improvement in pregnancy rate among CC-resistant PCOS infertile women might be expected.