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. 2018 Oct 15;2(12):1345-1356.
doi: 10.1210/js.2018-00225. eCollection 2018 Dec 1.

Recombinant Human FSH Treatment Outcomes in Five Boys With Severe Congenital Hypogonadotropic Hypogonadism

Ella Kohva  1 , Hanna Huopio  2 , Matti Hero  1 , Päivi J Miettinen  1 , Kirsi Vaaralahti  1 , Virpi Sidoroff  3 , Jorma Toppari  4 , Taneli Raivio  1
Affiliations

Recombinant Human FSH Treatment Outcomes in Five Boys With Severe Congenital Hypogonadotropic Hypogonadism

Ella Kohva et al. J Endocr Soc. .

Abstract

Context: Recombinant human FSH (r-hFSH), given to prepubertal boys with hypogonadotropic hypogonadism (HH), may induce Sertoli cell proliferation and thereby increase sperm-producing capacity later in life.

Objective: To evaluate the effects of r-hFSH, human chorionic gonadotropin (hCG), and testosterone (T) in such patients.

Design and setting: Retrospective review in three tertiary centers in Finland between 2006 and 2016.

Patients: Five boys: ANOS1 mutation in two, homozygous PROKR2 mutation in one, FGFR1 mutation in one, and homozygous GNRHR mutation in one. Prepubertal testicular volume (TV) varied between 0.3 and 2.3 mL; three boys had micropenis, three had undergone orchidopexy.

Interventions: Two boys received r-hFSH (6 to 7 months) followed by r-hFSH plus hCG (33 to 34 months); one received T (6 months), then r-hFSH plus T (29 months) followed by hCG (25 months); two received T (3 months) followed by r-hFSH (7 months) or r-hFSH plus T (8 months).

Main outcome measures: TV, inhibin B, anti-Müllerian hormone, T, puberty, sperm count.

Results: r-hFSH doubled TV (from a mean ± SD of 0.9 ± 0.9 mL to 1.9 ± 1.7 mL; P < 0.05) and increased serum inhibin B (from 15 ± 5 ng/L to 85 ± 40 ng/L; P < 0.05). hCG further increased TV (from 2.1 ± 2.3 mL to 8.6 ± 1.7 mL). Two boys with initially extremely small testis size (0.3 mL) developed sperm (maximal sperm count range, 2.8 to 13.8 million/mL), which was cryopreserved.

Conclusions: Spermatogenesis can be induced with gonadotropins even in boys with HH who have extremely small testes, and despite low-dose T treatment given in early puberty. Induction of puberty with gonadotropins allows preservation of fertility.

Keywords: FSH; hypogonadotropic hypogonadism; inhibin B; prepubertal.

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Figures

Figure 1.
Figure 1.
Treatment schemes of five boys with CHH on a timeline starting from each boy’s first hormonal therapy. White box represents r-hFSH; dashed box, hCG; and black box, T.
Figure 2.
Figure 2.
Markers of puberty and testicular function during r-hFSH treatment or combination of r-hFSH and T treatment in five adolescents with CHH: inhB, FSH, AMH, and TV. Patients 1 and 2, marked with a solid line, were treated with r-hFSH; patients 3, 4, and 5, marked with a dashed line, were treated with r-hFSH plus T.
Figure 3.
Figure 3.
Response to r-hFSH and hCG therapy in three boys with CHH. Schematics and individual responses for treatment in TV, progression of puberty (Tanner G and P stages), AMH, and inhB levels in (A) patient 1 (carrying ANOS1 mutation), (B) patient 2 (carrying homozygous GNRHR mutation), and (C) patient 3 (carrying homozygous PROKR2 mutation). Maximum sperm count and the time of sperm analyses are indicated by sperm symbols.
See this image and copyright information in PMC

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