Successful Pregnancies After Adequate Hormonal Replacement in Patients With Combined Pituitary Hormone Deficiencies

Fernanda A. Correa; Paulo H. M. Bianchi; Marcela M. Franca; Aline P. Otto; Rodrigo J. M. Rodrigues; Dani Ejzenberg; Paulo C. Serafini; Edmundo Chada Baracat; Rossana P. V. Francisco; Vinicius N. Brito; Ivo J. P. Arnhold; Berenice B. Mendonca; Luciani R. Carvalho

Disclosures

J Endo Soc. 2017;1(10):1322-1330. 

In This Article

Abstract and Introduction

Abstract

Context Women with hypopituitarism have lower pregnancy rates after ovulation induction. Associated pituitary hormone deficiencies might play a role in this poorer outcome.

Objective We evaluated fertility treatment and pregnancy outcomes in five women with childhood-onset combined pituitary hormone deficiencies (CPHD).

Patients and Methods Five women with CPHD were referred for fertility treatment after adequacy of hormone replacement was determined. Patients were subjected to controlled ovarian stimulation (COS) for timed intercourse, intrauterine insemination, or in vitro fertilization, according to the presence or absence of other infertility factors (male or tubal).

Results All women became pregnant. The number of COS attempts until pregnancy was achieved varied between 1 and 5. The duration of COS resulting in at least one dominant follicle varied between 9 and 28 days, and total gonadotropin consumed varied between 1200 and 3450 IU. Two patients with severely suppressed basal gonadotropin levels since an early age had a cancelled COS cycle. All pregnancies were singleton except one (monochorionic twin gestation). The gestational ages at birth ranged from 35 weeks to 39 weeks and 4 days; three patients underwent cesarean section, and two had vaginal deliveries. Only one newborn was small for gestational age (delivered at 35 weeks).

Conclusion Adequate hormonal replacement prior to ovarian stimulation resulted in successful pregnancies in patients with childhood-onset CPHD, indicating that hormone replacement, including growth hormone, is an important step prior to fertility treatments in these patients.

Introduction

Combined pituitary hormone deficiencies (CPHDs), defined as a deficiency of two or more pituitary hormones, can be congenital or acquired. The estimated prevalence of CPHD varies between 300 and 455 per million inhabitants, according to European data.[1] Mutations in transcription factors such as PROP1, POU1F1, GLI2, HESX1, LHX3, LHX4, SOX2, SOX3, and OTX2 are known genetic causes of congenital cases, but they are identified in only a small fraction of patients.[2]

Women with isolated hypogonadotropic hypogonadism (HH) have good pregnancy prospects after reproductive treatments.[3] In contrast, case reports and series reporting on the outcomes of ovulation induction in women with CPHD (involving HH) have shown a high number of cancelled cycles due to low or absent ovarian response to stimulation.[4,5] Also, lower pregnancy and live birth rates[4] and increased risk of obstetrical complications[6] have been reported in these women; multiple pregnancies had even poorer outcomes in this group.[7] Hence, it could be hypothesized that associated pituitary hormone deficiencies beyond gonadotropins have an adverse effect on fertility and pregnancy outcomes.[8]

Growth hormone (GH), which has multiple effects on the reproductive system, has been described as a possible treatment.[4,9,10] However, GH replacement during pregnancy carries some controversy in the literature, with some researchers advocating its usefulness and safety and others advocating its discontinuation due to increasing placental GH and consequently maternal insulin-like growth factor (IGF)-1.[11,12] Vila et al.[13] recently reported gestational data from a large cohort of women with GH deficiency (isolated or combined with other pituitary deficiencies) showing that the outcome of pregnancy was not influenced by the GH replacement therapy (GHRT) regimen. However, only 7.5% of pregnant patients in that cohort had stopped GHRT at some point before conception. Also, because it was not that study's objective, the effect of GHRT on women's fertility was not evaluated (i.e., the study does not report on the proportion of women who conceived in relation to the total number of patients attempting pregnancy); nor was it determined if this proportion changed due to the GHRT.

Women with CPHD, particularly those with severely suppressed luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels since childhood, have been reported to have lower serum antimullerian hormone (AMH) levels compared with women of the same age group without complete gonadotropin deficiency.[14,15] The serum AMH levels and the ovarian antral follicle count (AFC) through transvaginal sonography are used to estimate the ovarian follicular reserve (ovarian reserve tests) and, therefore, to predict the ovarian response to stimulation with exogenous gonadotropins.[16,17] However, it has been hypothesized that AMH levels probably do not accurately reflect the ovarian follicular reserve or predict the efficacy of fertility treatments in this group of patients. Still, to our knowledge, there has been no report of ovarian stimulation outcomes in women with CPHD in relation to their ovarian reserve tests results and basal gonadotropin levels.

We present here the clinical and hormonal data, the previous ovarian reserve status, pregnancy outcomes, and puerperium details of five patients with childhood-onset CPHD who had successful pregnancies.

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