Low-dose gonadotropin induction of ovulation in anovulatory women: still needed in the age of IVF

Abstract

26Low-dose, step-up gonadotropin is the treatment of choice for women with polycystic ovary 27 syndrome (PCOS) who have not conceived after anti-estrogen treatment, and as an effective 28 alternative to pulsatile GnRH in women with hypogonadotropic hypogonadism (HH). There 29 has been, however, no large-scale, comparative study between the two groups using low-30 dose gonadotropins. Here we performed a retrospective, comparative analysis, in a single 31 clinic database, of efficacy and safety of induction of ovulation using low-dose 32 gonadotropins in 364 Women with PCOS and 80 women with HH. 33The rate of ovulation was high in both PCOS (83%) and HH (84%) but mono-follicular, 34 ovulatory cycles were more prevalent in PCOS than in HH (77% vs 53%, p<0.0001) and the 35 proportion of cycles that were abandoned was higher in HH than in PCOS (25% vs 15%, 36 p<0.0001). The median threshold dose of gonadotropin required to induce ovulation was 37 75iu/day in PCOS and 113iu/day in HH (p<0.001) and the range of doses was greater in HH 38women. Forty-nine percent of women with PCOS and 65% of those with HH conceived 39 (more than 90% within 6 cycles of treatment) and had a least one pregnancy. Multiple 40 pregnancies (all twins) occurred in only 4% of women with PCOS and 5% of those with HH. 41These findings emphasise the efficacy and safety of low-dose gonadotropin treatment for 42 both clomiphene-resistant women with PCOS and those with HH. These results highlight the 43 importance of choosing the more physiological approach of gonadotropin induction of 44 ovulation in both groups as the most appropriate treatment, in preference to IVF. 45 46

Late Effects of Parasellar Lesion Treatment: Hypogonadism and Infertility

“…Women and girls with parasellar lesions are at risk of infertility because of the potential detrimental effects of surgery and radiotherapy on the hypothalamic-pituitary axis. Retrospective studies report pregnancy rates of between 47 and 76% amongst women with hypopituitarism [86][87][88][89][90]. In childhood, both hypopituitarism and isolated HH may lead to smaller uterine dimensions and ovarian volume compared with healthy controls [91].…”

“…COS protocols for assisted reproduction in women with HH are described in Table 3. The reported pregnancy rates after COS amongst HH women vary wildly, from 19.4 to 100%, with a 3.6-41.7% risk of multiple pregnancies [88][89][90][95][96][97][98][99][100]. Higher gonadotropin doses are generally used than in patients with other causes of infertility [101].…”

Hormonal Treatments in the Infertile Women

“…In the most recent study, the threshold HMG dose was 75 IU in about 20% of patients, while 19% of patients required doses higher than 150 IU/day. The age and BMI of the hypogonadotropic women that required HMG doses >150 IU/day were higher than the patients with HMG threshold less than 150 IU/day (White et al 2018).…”

“…However, with both practices, there is a significant risk for multiple pregnancies, despite the goal of ovulation induction to select a single follicle. More recently, it was proposed that HCG should be given when the leading follicle is 18 mm, with no more than three follicles !15 mm (White et al 2018).…”

The 40th anniversary of human IVF: time to celebrate and time to reflect

“…But this is often ignored in reproductive medicine. Specific therapy for anovulation as Stephen Franks points out in this issue is more successful than IVF and cheaper (White et al 2018). Selected cases of tubal disease or pelvic adhesions may have a better prognosis with microsurgery or laparoscopic surgery.…”