Assessing Ovarian Reserve



Fig. 3.1
A validated model of serum AMH from conception to menopause [20]





Current Data on AMH in Children Receiving Cancer Therapy


In women treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin lymphoma during childhood, AMH was noted to be lower compared with healthy women and women treated without MOPP [21]. In a larger series of 185 childhood cancer survivors, although the cohort’s median AMH concentration was no different from controls, the AMH levels were lower than the 10th percentile of normal values in 27 % of the survivors. Survivors treated with three or more procarbazine containing chemotherapy cycles and those treated with abdominal or total body irradiation had significantly lower AMH levels than controls [22]. In adult women with cancer, AMH declines during treatment followed by recovery in some patients, with the rate of recovery determined by the pretreatment AMH level [23].


Ovarian Reserve Testing as a Predictor of Menstrual Pattern and Fertility


Ovarian reserve testing to predict the risk of acute ovarian failure and early menopause and future fertility in females prior to cancer therapy would allow us to better target patients for ovarian preservation procedures [24]. In adults, one small series in breast cancer survivors demonstrated that inhibin B and AMH prior to therapy were significantly lower in the women who went on to develop amenorrhea after treatment [25]. Similarly, in 46 adolescent and young adult women with a new cancer diagnosis requiring chemotherapy, pretreatment AMH levels were associated with the rate of recovery of AMH after treatment. Participants with a pretreatment AMH level >2 ng/mL had a faster rate of recovery of AMH after chemotherapy compared to participants with pretreatment AMH levels </= 2 ng/mL [23].

In addition, the ability of ovarian reserve testing to predict time to menopause and ovarian insufficiency on survivors who are menstruating would be very useful in order for them to plan posttreatment fertility preservation and other therapies [24]. In a prospective study of breast cancer survivors who were still menstruating, the patients who had cessation of menses 2 years later were more likely to have lower AMH and higher FSH at study entry [24].

To date there is no data regarding the ability of ovarian reserve testing to predict risk of premature menopause in prepubertal girls before therapy or in survivors of childhood cancer.


Effect of Female Hormones on Ovarian Reserve Testing


Many young women who receive cancer therapy are placed on birth control pills to regulate menses or estrogen replacement therapy when ovarian insufficiency is suspected. It is important to understand the effect of this treatment on ovarian reserve testing. A study evaluating ovarian reserve testing in 887 healthy women, 18–46 years old, found that AMH, antral follicle counts, and ovarian volume were all significantly decreased in oral contraception users when compared to nonusers [26]. In a small study comparing young cancer survivors on birth control pills with control women on the pills during the third week of pills (while taking active pills), there were no differences noted in FSH, inhibin B, estradiol, or AMH, but the AFC was lower in the cancer survivors [27].

Several studies have evaluated ovarian reserve testing during the placebo or pill-free week comparing survivors with spontaneous menses and those on birth control pills. Results from these studies are contradictory, use small samples, and compare populations exposed to cancer therapy to each other and not healthy age-matched controls [21, 28]. In addition, there are no studies which evaluate whether ovarian reserve testing in women on female hormones is predictive of menstrual function or fertility.


Conclusions

Ovarian reserve testing has been extensively studied in healthy women who seek infertility treatment but not in young girls receiving cancer therapy. This population would benefit significantly from rigorous data regarding ovarian reserve testing which may predict their risk of early menopause and assess the risk and benefits of fertility preservation options. Research in this population is limited by the fact that the numbers of girls at individual institutions are low as well as the fact that the outcome of interest (the ability to achieve successful pregnancy) may be far in the future [27]. Future multicenter studies with collaborative efforts of reproductive specialists, oncologists, and patient advocates will need to be performed.



References



1.

Byrne J, et al. Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol. 1992;166(3):788–93.CrossRefPubMed


2.

Green DM, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27(14):2374–81.CrossRefPubMedPubMedCentral

Sep 24, 2017 | Posted by in GYNECOLOGY | Comments Off on Assessing Ovarian Reserve
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