Extended LH administration as a strategy to increase the pool of recruitable antral follicles in hypothalamic amenorrhea: evidence from a case series

Abstract

Abstract New evidence is indicating a growing role of LH in promoting ovarian follicular growth and maturation, even at the early stages. LH seems to enhance the transition of follicles to the antral stage hence leading to an increase in the so-called functional ovarian reserve (recruitable antral follicles). Hypogonadotropic hypogonadism is characterized by low, and sometimes undetectable, serum LH and FSH levels, which may indeed explain the low anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) found in patients affected by this condition. We report here the cases of two young women affected by hypothalamic amenorrhea (HA) that presented for fertility treatment with very low functional ovarian reserve. The two patients were treated with exogenous LH for 1 and 2 months (extended LH administration: ELHA) at the dose of 187.5 IU LH every day and 150 IU LH every other day, respectively. In both the cases there was an increase in serum AMH levels and in the AFC. In one patient, the AMH and AFC increased from a baseline 1.3 ng/ml and 8 to 2.3 ng/ml and 14 at end of treatment, respectively. In the second case, serum AMH and AFC increased from 0.4 ng/ml and 6 to 1.6 ng/ml and 13, respectively. One patient underwent ovarian stimulation before and after ELHA, showing an increase in the number of mature oocytes recruited (3 versus 8 metaphase II (MII) oocytes before and after, respectively). The second patient underwent an IVF cycle after ELHA resulting in the retrieval of six MII oocytes and an ongoing pregnancy following transfer of a single blastocyst. Women with HA are characterized by chronic, low levels of gonadotrophins, which may impact not only on the cyclic recruitment of follicles but also the progression of small growing follicles through the first stages of folliculogenesis. Some women with HA may in fact show very low serum AMH and AFC. Our case series shows that the administration of LH at a dose of at least 150–187.5 IU every day or every other day may contribute to a clinically evident increase in the functional ovarian reserve (AFC), and probably accounts for a positive effect of LH on the progression of follicles throughout the early stages of folliculogenesis.