Pregnancy and Avoiding Premature Menopause after Chemotherapy

Fertility Preservation
Chemotherapy can render a woman infertile and cause premature menopause (premature ovarian insufficiency). Receiving chemotherapy in no way infers that a woman cannot become pregnant and bring her baby to term. There are, however, several hindrances that can cause issues. Most oncologists recommend women wait six months to 2 years after chemotherapy before trying to get pregnant. Waiting six months diminishes the risk of egg damage by chemotherapy. The 2-year recommendation is based on the knowledge that cancer recurrence is highest in the first two years after treatment. In addition, many women with estrogen receptor-positive cancers will be on anti-estrogen therapy such as tamoxifen for 5-10 years, during which time pregnancy is not recommended. However, the younger a woman is when receiving chemotherapy, the more likely she will regain ovarian function. Below are some strategies to improve the chances of a successful pregnancy and reduce the risk of premature ovarian insufficiency.

Embryo freezing
In embryo freezing, or cryopreservation, mature eggs are removed from the female and placed in a sterile dish with several thousand sperm. The goal is for one of the sperm to fertilize an egg. The process is called in vitro fertilization, or IVF. The embryo is then frozen, and after treatment, it is thawed and put back into the female’s uterus to achieve a pregnancy. It is essential to know that the younger the woman’s age at IVF, the higher potential for pregnancy.

Egg freezing
Though not used as long as embryo freezing, egg freezing is a good choice for women who do not have a partner or do not want to use donor sperm. In egg freezing, the surgeon removes mature eggs from the female then freezes them before being fertilized with sperm. When the woman is ready to become pregnant, the eggs can be thawed, fertilized by a partner or donor sperm, and implanted into her uterus to achieve a pregnancy.

Ovarian tissue freezing
Though still experimental, this procedure involves the removal of part of one ovary using laparoscopy. The surgeon cuts the ovarian tissue into small strips, which are frozen and stored. After cancer treatment is completed, the tissue is thawed and placed in the pelvis. Once the tissue begins to function again, eggs are collected and fertilized in the lab.

Gonadotropin-releasing hormone agonist improves the chances of pregnancy and reduces the risk of premature ovarian insufficiency (premature menopause)
Gonadotropin-releasing hormone (GnRH) is a chemical released by the hypothalamus in the brain, which stimulates the release of follicle-stimulating hormone and luteinizing hormone from the pituitary gland. During childhood, the level of this hormone is low. But as puberty arrives, there is an increase in the release of GnRH, which triggers the onset of sexual maturation. The level of GnRH is controlled by testosterone in men and estrogen plus progesterone in women. At first blush, one might think that a GnRH agonist would increase the hormone concentration. A rise does occur; however, it is only a brief surge. Ovarian function eventually turns off as the concentration of GnRH persists. It has been known for some time that women who receive GnRH agonists during chemotherapy have an improved chance of maintaining ovarian function and an improved chance of becoming pregnant. A recent article in the J Natl Cancer Inst (2021) by Lambertini et al. reported on a multicenter randomized phase 3 trial from 16 centers in Italy (PROMISE-GIM6 trial). Patients were randomized to neoadjuvant (preoperative) chemotherapy alone or combined with triptorelin (GnRH agonist). The endpoint of the study was premature ovarian insufficiency with secondary endpoints of overall survival, disease-free survival, and post-treatment pregnancies.

Of the 281 patients randomized, 80% had hormone receptor-positive breast cancer. The median follow-up was 12.4 years. Researchers reported no difference in disease-free or overall survival. There were only 13 pregnancies in the entire study cohort, with no difference between the two arms of the study. Most importantly, one year from the completion of cytotoxic therapy, there was a significant reduction in premature ovarian insufficiency. At five years, ovarian function recovered from 64% in patients not receiving GnRH to 73% in those that did.

In summary, several strategies exist to improve the chance of a successful pregnancy. Furthermore, in a recent study from Italy, the administration of GnRH to women undergoing chemotherapy was safe. No differences were noted in survival between women receiving GnRH and those who did not. You should also note that this was the largest study of its kind to include a substantial number of estrogen receptor-positive breast cancers. The study also demonstrated a reduction in premature ovarian insufficiency (premature menopause) in the group receiving GnRH. It is important that women discuss their options regarding future pregnancy and techniques for reducing early menopause before beginning chemotherapy.