Is AMH a regulator of follicular atresia?

We discuss the hypothesis that AMH is an intraovarian regulator that inhibits follicular atresia within the human ovary. Several indirect lines of evidence derived from clinical and basic science studies in a variety of different patient populations and model systems collectively support this hypothesis. Evidence presented herein include 1) timing of onset of menopause in women with polycystic ovary syndrome, 2) site of cellular origin and timing of AMH production, 3) AMH's influence on other critical growth factors and enzymes involved in folliculogenesis, and 4) AMH's inhibition of granulosa apoptosis. If this hypothesis is true, it may provide insight for treatment strategies for prevention and treatment of premature ovarian insufficiency, slowing natural ovarian aging, and/or delaying eventual ovarian failure. Such findings may lead to the development of 1) AMH agonists for retarding the onset of menopause and/or as a chemoprotectant prior to cancer therapy and 2) AMH antagonists for the treatment of PCOS.

The type 2 anti-Müllerian hormone receptor has splice variants that are dominant-negative inhibitors.

Anti-Müllerian hormone (AMH) has both paracrine and hormonal actions that occur at different AMH concentrations, and in cells with different densities of its specific receptor (Amhr2). This diversity is not explained by canonical AMH signaling. We report that Amhr2 has two splice variants: Amhr2Δ2 (AMH binding site) and Amhr2Δ9/10 (kinase domain). Both spliced variants inhibit AMH signaling in a reporter assay. The mRNA for the spliced variants was relatively less abundant than Amhr2 mRNA in all tissues. This suggests that the physiological function(s) of the receptor variants may be restricted to specific cellular/subcellular sites and/or to the transport of AMH.

Anti-Müllerian hormone trend after laparoscopic surgery in women with ovarian endometrioma.

Operative laparoscopy is the gold standard in the treatment of endometriotic ovarian cysts. Excisional surgery is the best technique to prevent recurrences and improve symptoms but it may result in ovarian reserve damage due to the removal of healthy ovarian cortex. The aim of this study was to investigate the extent of the ovarian reserve damage after stripping technique of unilateral endometriomas, by dosing the Anti-Müllerian Hormone (AMH). This prospective study was conducted at the Center of Minimally Invasive Pelvic Surgery of the Department of Health of Woman and Child, University of Padua, from October 2010 to June 2012. Twenty-five women underwent excision of monolateral endometriosis ovarian cyst by stripping without accessing a bipolar coagulation and performing an intracortical suture. The AMH serum levels were estimated in the early proliferative phase of the cycle, before surgery (time 0), 24 h after surgery (time 1), the first menstrual cycle after surgery (time 2) and the third menstrual cycle after surgery (time 3). We found a nonstatistically significant decreases in serum AMH levels after surgical excision of the cysts. Our results suggest that an appropriate surgical technique, without the use of the bipolar coagulation of ovarian border, does not determine a significant reduction of ovarian reserve.

Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-Müllerian hormone levels.

OBJECTIVE: To evaluate the ovarian reserve changes after laparoscopic cystectomy, we prospectively evaluated pre- and postoperative serum anti-Müllerian hormone (AMH) level, and ovarian volumes. DESIGN: Prospective longitudinal study. SETTING: University Hospital. PATIENT(S): Twenty women with benign ovarian masses participated; endometrioma [13], mature teratoma [6], and mucinous cystadenoma [1]. Seven patients had bilateral ovarian masses. INTERVENTION(S): All patients had undergone laparoscopic ovarian cystectomy. Serum AMH levels were serially measured: preoperative, 1 week, 1 month, and 3 months after operation. Volumes of total ovary and ovarian mass were measured by 3D ultrasonography before operation. MAIN OUTCOME MEASURE(S): Postoperative serum AMH level and ovarian volume. RESULT(S): Median AMH level was 2.23 ng/mL (95% confidence interval [CI] 1.35-3.41 ng/mL) before operation, but reduced to 0.67 ng/mL (95% CI 0.44-1.70 ng/mL) at the first week postoperatively and then increased to 1.14 ng/mL (95% CI 0.79-2.36 ng/mL) in the first month and 1.50 ng/mL (95% CI 0.58-3.26 ng/mL) in the third month. The serum AMH level after 3 months postoperatively was recovered to about 65% of the preoperative level. The serum AMH level at postoperative 1 week was more decreased in endometrioma compared with nonendometrioma (33.9% vs. 69.2% of preoperative level), and in bilateral group compared with unilateral group (16.9% vs. 62.9%). CONCLUSION(S): This study suggests that ovarian reserve could be reduced after laparoscopic cystectomy; however, it could be restored thereafter up to 3 months postoperative in reproductive women.

Anti-Müllerian hormone and ovarian dysfunction.

Anti-Müllerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are elevated, which indicates its potential relevance in PCOS diagnosis and management. AMH represents a useful clinical marker for the assessment of ovarian reserve in cases of subfertility caused by advanced age in women. A potential role for AMH in dominant follicle selection has also been suggested. Future challenges comprise the availability of a well-standardized assay and the development of AMH agonists and antagonists as possible tools to manipulate ovarian function for contraception or ovarian longevity.