Gonadotropin induction of ovulation

Gonadotropins have been widely used worldwide for many years to induce ovulation. Three main exogenous gonadotropins are used for ovulation induction—follicle stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG). Currently, these gonadotropins are available in the urinary (with the exception of LH) and recombinant forms. FSH (± LH) is used to stimulate follicular development and hCG is used to trigger ovulation of the mature follicle(s). Indications for gonadotropin ovulation induction include hypogonadotrophic hypogonadism and clomifene-resistant normogonadotrophic anovulation. Gonadotropins are also used for controlled ovarian hyperstimulation in conjunction with intrauterine insemination in ovulatory women treated for unexplained or mild male factor infertility. Two main regimens of gonadotropin ovarian stimulation are used, namely step-up and the step-down protocols. The choice of gonadotropin preparation and treatment regimen depends on the underlying ovarian dysfunction. Strict monitoring of gonadotropin treatment with implementation of strict cancellation criteria are recommended to minimise the risks of ovarian hyperstimulation and multiple pregnancy.     

Methods of ovulation induction

Basing on the mechanism of the endocrine regulation of the reproductive events in the women causes and therapy of the endocrine sterility are discussed. Causes of endocrine sterility are divided into the entities hyperprolactinemic, hyperandrogenemic, hypo- and dysgonadotropic hypogonadism. Concerning these disturbances the specific therapeutic opportunities with the inhibitor of the prolactin secretion, with antiandrogenes, corticosteroids, antiestrogens, gonadotropins or gonadotropin-releasing hormone, respectively, are summarized. With a proposed scheme for diagnostic and therapeutic use an effective and economic proceeding in the treatment of the endocrine caused female sterility is intended.     

Modern trends in ovulation induction

Patients with anovulatory infertility, who received treatment at one unit over a four year period, were assessed to determine the pregnancy rate and the incidence of complications while undergoing ovulation induction with gonadotropins. The patients in this group who had further in vitro fertilization (IVF) treatment were followed up, and the outcome in IVF cycles was assessed. Data from a total of 75 patients, who had completed 91 episodes of treatment involving 273 cycles of ovulation induction over a 4-year period in a University-affiliated teaching hospital, was analysed retrospectively. The cumulative pregnancy rate was 34% after three ovulation induction cycles, and was 46% overall. The clinical pregnancy rate per cycle was 15.4%, and per ovulatory cycle was 21%. The multiple pregnancy rate was 12%, and there were no cases of ovarian hyperstimulation syndrome (OHSS). In this group of patients undergoing ovulation induction, the multiple pregnancy rate was 12% and there were no cases of ovarian hyperstimulation syndrome (OHSS). The multiple pregnancy rate was 17%. Our result indicate that anovulatory patients benefit from ovulation induction with gonadotropins prior to IVF treatment.     

New advances in ovulation induction

PURPOSE OF REVIEW: To review recent advances in ovulation induction. RECENT FINDINGS: Aromatase inhibitors can replace clomiphene citrate as ovulation-inducing substances. The most widely used aromatase inhibitor for this purpose is letrozole and the optimal dose is 5 mg daily for 5 days. Compared to clomiphene citrate, it is associated with a thicker endometrium and a better pregnancy rate. It is as effective as gonadotropin but yet less expensive. The overall rates of congenital malformation among newborns conceived after infertility treatment with letrozole or clomiphene citrate are similar. When letrozole is combined with gonadotropin, it leads to lower gonadotropin requirements with pregnancy rates comparable to gonadotropin treatment alone. Another promising aromatase inhibitor is anastrazole. Recent evidence suggests that luteinizing hormone activity in human menopausal gonadotropin modifies follicular development so that fewer intermediate-sized follicles develop. Compared to the use of follicular stimulating hormone only, human menopausal gonadotropin is associated with less ovarian hyperstimulation. SUMMARY: Aromatase inhibitors are alternative drugs to clomiphene or gonadotropin for ovulation induction or superovulation.     

Clomiphene citrate and ovulation induction

Clomiphene can be used to treat anovulation due to hypothalamus or pituitary gland dysfunction, and it normalizes the luteal phase in stimulated patients. It can be used to estimate ovarian follicle reserve, and may be predictive of ovulation in women aged >/=35 years or with failed IVF. Contraindications include risk of congenital anomalies, chronic liver disease and visual disorders. Clomiphene may impair fertility through its effects on cervical mucus and in causing various endometrial dysfunctions. However, if clomiphene is administered in 50 mg doses, side-effects are avoided and efficacy is similar to that of a 100 mg dose, although daily dosages of 200 mg/day over 5 days can induce ovulation in approximately 70% of treated patients. Gonadotrophin concentrations increase up to days 5-9 when follicles are selected, and clomiphene is effective in patients with polycystic ovary syndrome (PCOS). Fifty percent of normal patients conceive, a value perhaps biased by the antagonistic effects of clomiphene on cervical mucus in some women. Clomiphene is valuable for IVF, and is used by some clinics in combination with HMG or recombinant FSH. Resistance to clomiphene can develop, and human chorionic gonadotrophin may be needed to induce ovulation in clomiphene cycles. Corticosteroids and human menopausal gonadotrophin (HMG) can be combined with clomiphene for stimulation, its combination with HMG long having been a standard protocol in assisted reproduction. PCOS patients may become insulin resistant, a condition improved by the administration of metformin. Other adverse effects include multiple pregnancies, an increase in the rate of multiple births, ovarian hyperstimulation and unsubstantiated claims of ovarian cancer.     

Aromatase inhibitors in ovulation induction

The new third generation aromatase inhibitors are extremely potent and specific oral inhibitors of estrogen production. We reported the success of using aromatase inhibitors for induction of ovulation in World Health Organization (WHO) type II anovulatory patients. Promising pregnancy rates were associated with the use of aromatase inhibitors for induction of ovulation in these women. In addition, the use of aromatase inhibition in conjunction with gonadotropin injection was associated with a significant reduction in the gonadotropin dose required for optimum controlled ovarian hyperstimulation. We believe that these oral agents are efficient and safe and have many advantages compared with clomiphene citrate (CC). We propose that aromatase inhibitors will replace CC in the future as the new primary treatment for ovulation induction. In this review, we present an update on the use of aromatase inhibitors for induction of ovulation and we discuss several new areas of potential interest regarding the use of aromatase inhibitors, either alone or together with recombinant follicle-stimulating hormone (FSH) for infertility treatment. Further research in these areas may demonstrate an expanded role in assisted reproductive technologies.     

促排卵临床应用进展

促排卵是辅助生殖临床的重点、难点,促排卵方案的正确应用关系到所获卵母细胞的数量和质量,是决定辅助生殖成功率的关键一环。关于促排卵的研究层出不穷,涉及方方面面。近年来,出现了一些新的促排方案,如微刺激促排卵方案、自然周期IVF;一些新的促排卵药物,如来曲唑、GnRH拮抗剂;还有一些促排方案从小范围应用到逐渐推广、流行。但各种方案的利弊目前还未形成清晰、统一的认识,还需进一步研究证实。