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Hormone replacement before fertility treatment increases pregnancy chance in hypopituitarism
Women with childhood-onset combined pituitary hormone deficiencies have successful pregnancies when treated with adequate hormone replacement before ovarian stimulation, according to findings published in the Journal of the Endocrine Society.
Fernanda de Azevedo Correa, MD, PhD, of the University of São Paulo, and colleagues evaluated five women with childhood-onset combined pituitary hormone deficiencies to evaluate fertility treatment and pregnancy outcomes.
Participants were aged 25 to 37 years at the beginning of infertility treatment, and once the desire to conceive was expressed they were referred to the Infertility Care Unit. Before ovarian stimulation treatment, growth hormone was reinstituted or optimized in all participants. A regimen of oral estradiol valerate plus levonorgestrel replaced conjugated estrogens tablets and medroxyprogesterone acetate or oral contraceptive pills with 7-day intervals between cycles.
One dominant follicle resulted between 9 and 28 days of controlled ovarian stimulation, and total gonadotropin consumed ranged from 1,200 IU to 3,450 IU. A controlled ovarian stimulation cycle was canceled in two participants with severely suppressed basal gonadotropin levels.
All women became pregnant, and all were singleton births except for one set of monochorionic twins.
Infants were born between 35 to 39 weeks and 4 days’ gestation; three were delivered by cesarean section, and the other two were vaginal deliveries. Only one infant was small for gestational age, and all six were healthy without any signs of hypopituitarism.
“Optimized hormonal replacement, including GH, in women with childhood-onset hypopituitarism resulted in successful pregnancies and healthy babies after individualized fertility treatment,” the researchers wrote. “Diminished ovarian reserve tests should not preclude fertility treatment in these women.” – by Amber Cox
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Fertility is often affected in women with hypopituitarism (central adrenal insufficiency, central hypothyroidism, diabetes insipidus and growth hormone deficiency) regardless of its cause, and natural pregnancy is thus rare. A poorer outcome has been reported when hypopituitarism is diagnosed at a young age. The best regimen of glucocorticoid replacement in pregnancy is not well defined. Hydrocortisone is the preferred physiologic replacement in pregnancy, as it does not cross the placenta. Doses are usually adjusted based on signs and symptoms, while some groups (eg, the Endocrine Society’s 2016 guideline for management of hypopituitarism) advocate increasing hydrocortisone doses by 20% to 40% in the third trimester. Pregnant women also require increased thyroid replacement to maintain desired levels for pregnancy. Desmopressin doses are frequently, but not always, increased for diabetes insipidus during pregnancy. However, the data are more limited on the role of GH replacement. Based on a recent large, albeit retrospective, multicenter study, approximately half of women discontinue GH replacement during pregnancy, as efficacy and safety have not been clearly established, and furthermore, the placenta produces GH. The present prospective study details management of five women with childhood-onset hypopituitarism who were referred to fertility treatment after hormonal replacement optimization. Notably, all patients had GH deficiency and GH replacement was either restarted or optimized (0.3 to 1.0 mg daily) prior to ovarian stimulation; three patients continued the GH throughout pregnancy. There were one twin pregnancy, one perinatal complication (intrauterine growth restriction with fetal distress), one fetal malpresentation and three cesarean deliveries, but all six infants/toddlers were healthy with no signs of hypopituitarism at the conclusion of the study. Women require a multidisciplinary team for fertility induction and hypopituitarism management before and throughout pregnancy. However, with appropriate hormonal replacement, pregnancy can be uneventful with a healthy infant.