Clinically, hCG has proven successful at inducing and/or
maintaining spermatogenesis alone or in combination with FSH
in patients with hypogonadotropic hypogonadism (HH). HH is an
uncommon but treatable cause of male factor infertility classically
considered secondary to pathology of the hypothalamus or pituitary
gland as seen with Kallman’s syndrome, Prader–Willi syndrome,
panhypopituitarism from prolactinomas, tumors, infection or radiation,
or idiopathic causes.21 Recently, recognition that the increasingly
common use of exogenous TRT and/or AAS can also induce HH,
also known as ASIH, with associated diminished spermatogenesis.
Therefore, men with azoospermia or severe spermatogenic defects due
to classic HH serves as a useful context in whom to appreciate the effect
of gonadotropins upon spermatogenesis clinically. However, due to the
uncommon prevalence of HH, high-quality data are lacking and most
are limited to case reports and retrospective series.41
Historically, treatment approaches for HH have focused upon
physiologic, pulsatile GnRH therapy to induce secondary sex
characteristics and spermatogenesis with reported pregnancy rates
as high as 80%.42,43 However, widespread use of pulsatile GnRH is
inherently limited due to the need for an external pump for periodic
hormone release, cost, and requirement of a functionally intact
pituitary gland to appropriately respond to hypothalamic signals.44
Alternatively, treatment with injectable gonadotropin regimens has
demonstrated equivalent clinical efficacy compared with GnRH for
triggering spermatogenesis based upon a recent meta-analysis.44
Therefore, gonadotropins offer patients an efficacious and more
convenient treatment approach.45 FSH given alone or in combination
with testosterone has proven unsuccessful at inducing spermatogenesis
or maintaining spermatogenesis in those previously induced with
hCG/FSH (hCG 1500 IU and HMG 150 IU both subcutaneous
and 3 times per week), confirming the need for maintenance of
elevated ITT.46
However, long-term use of hCG alone can induce
spermatogenesis in up to 70% of patients, with a greater effect seen
in men with initial testis length >4 cm, but further improvement is
appreciated with the addition of FSH (HMG) suggesting a timelier
recovery with both gonadotropins.47 The success of inducing
spermatogenesis with a combination of hCG and FSH is supported
by several studies (Table 1).41,42,45,48–53 In these data, most begin by
stimulating endogenous testosterone production with trial of hCG
alone with doses ranging from 1500 to 5000 IU 2–3 times per week
titrated according to serum testosterone levels. Most experts treat
with hCG alone for 3–6 months after which a certain number of cases
will result in spermatogenesis induction. In those without adequate
spermatogenesis induction, treatment proceeds with the addition of
FSH with doses ranging from 75 to 400 IU 2–3 times per week titrated
according to semen analysis results. Success defined as induction of
spermatogenesis with >1–1.5 × 106
ml−1 sperm was reported to occur
in 44%–100% of patients treated for 6–144 months.52 Pregnancy rates,
when reported, were observed in 40%–75% of patients usually at sperm
concentration levels below “normal.”42,51,54 Factors predicting success
include larger baseline testis volume, previous natural gonadotropin
exposure (normal puberty), and repeated treatment cycles whereas
previous exogenous testosterone exposure and cryptorchidism
portend a slower response although these findings are variable.42,55
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Originally Posted by Little76
