Authors: Yasmin Gosiengfiao, MD and Veronica Gomez-Lobo, MD

Fertility is defined as the ability to produce young [1]. Conversely, infertility is defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse [2]. Having pregnancies thus would be the best measure of fertility. The Childhood Cancer Survivor Study (CCSS) showed that female survivors of childhood cancer are less likely to have ever been pregnant compared to their female siblings, especially those with a summed alkylating agent dose (AAD) score of three or four or who were treated with lomustine or cyclophosphamide [3]. However, using pregnancies as a measure of fertility limits one to waiting until a childhood cancer survivor has grown into an adult and has attempted to get pregnant. Even among adults, not all adult women attempt to get pregnant. So, surrogate measures of fertility are necessary to assess the effect of chemotherapy/radiation/surgery on fertility. Several markers have been used to assess ovarian and testicular reserve as surrogate measures of fertility. These markers can be affected by:

  • Age at time of testing
  • Age at time of chemotherapy and/or radiation therapy and/or gonadal surgery
  • Type and cumulative dose of chemotherapy received
  • Dose and target site of radiation received
  • Genetic factors
  • Other illnesses
  • History of infertility

Markers of Ovarian Reserve

The initial number of follicles in humans is established in utero at 5 months gestation with approximately 10 million primordial follicles. This number of follicles (or ovarian reserve) diminish in utero and after birth to nearly 500,000 at menarche and continue to decline thereafter.

It should be noted that most of the research regarding markers of ovarian reserve has been performed in women seeking treatment for infertility [4]. 

The following have been used as measures of ovarian reserve:

Menstrual cycles/amenorrhea (acute ovarian failure/premature menopause)

Endocrine hormones: Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estradiol, Inhibin B

 Antral follicle counts

Anti-Mullerian hormone (AMH)

Guidelines for assessing ovarian reserve:

Currently, the only available guideline regarding the assessment of ovarian reserve is from the Children’s Oncology Group (COG). This guideline applies to long-term survivors of childhood, adolescent and young adult cancer and is available at http://www.survivorshipguidelines.org/. The recommendations include checking pubertal (onset and tempo), menstrual and pregnancy history annually as well as Tanner staging annually until sexually mature. They also recommend checking a baseline FSH, LH and estradiol at age 13 and as clinically indicated in patients with delayed or arrested puberty, irregular menses, primary or secondary amenorrhea, and/or clinical signs and symptoms of estrogen deficiency. [21] There are currently no guidelines available on the use of AFC and AMH.

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