Leptin linked to Unexplained Infertility

Leptin linked to unexplained infertility
Issue 13: 25 Jun 2007
Source: Journal of Reproductive Immunology 2007;in press

New study results suggest that the cytokine leptin may be involved in the pathophysiology of unexplained infertility.

Leptin is a hormone produced in adipose tissue and in ovarian follicles (both in granulosa and cumulus cells). It is involved in cycles regulating energy intake and energy expenditure, affecting appetite and metabolism. Leptin is also understood to play a role in regulating the menstrual cycle.

In the new study, researchers from centers in Diyarbakir and Ankara, in Turkey, measured leptin levels in 27 women with unexplained infertility and 30 fertile women matched for age and body mass index.

The women with unexplained infertility (mean age 29.3 years, range 23-38 years) had a history of failing to achieve pregnancy after at least 1 year of unprotected intercourse. They had adequate ovulation, tubal patency, a normal uterine cavity, and a cycle day 3 follicle-stimulating hormone concentration less than 15 mIU/ml. The women also had four or more antral follicles in the early follicular phase, and their partners had normal results from semen analysis.

The women in the control group (mean age 28.9 years, range 19-39 years) did not have a history of infertility, and had had at least one live birth within the previous 2 years. Women who smoked, were obese, had a history of cerebrovascular, cardiovascular or thromboembolic events, or had a history of hypertension or diabetes, were among those excluded from the study.

The researchers took serum samples from the women in the morning after an overnight 12-hour fast, on the follicular phase of the menstrual cycle (day 3).

In their paper scheduled for publication in the Journal of Reproductive Immunology, they report that mean serum leptin levels were significantly higher in the unexplained infertility group than in the fertile group: 7.0 ng/ml (range 4.2-10.4 ng/ml) compared with 3.4 ng/ml (range 1.3-6.2 ng/ml) respectively.

Subgroup analyses showed that the significant difference remained when considering women of normal weight (mean serum leptin level 7.2 ng/ml, compared with 3.5 ng/ml in the control group) and when considering women who were overweight (mean serum leptin level 6.8 ng/ml, compared with 3.3 ng/ml in the control group).

Regulating reproduction?
Discussing their findings, the researchers cite previous suggestions in the literature that leptin may have a dual role in regulating reproduction: low levels may negatively influence the neuroendocrine regulation of reproduction, with a threshold level required for normal reproductive function, while higher levels of leptin may negatively influence normal ovarian function and/or embryo development and viability.

They conclude that “serum leptin levels were elevated in women with unexplained infertility. Furthermore, this study reports a significant increase in serum leptin levels in the unexplained infertile group compared with the fertile group.” The findings need to be replicated in larger numbers of women, and serum and peritoneal fluid leptin levels should also be compared, the researchers add.