Download Dec 21, 2010 Voice 114

Dec 21, 2010
Voice 114
Endocrine Dysfunction as a Determinant of Human Infertility
Infertility is one of the most important and underappreciated reproductive health problems in developing
countries. Infertility can be defined as the failure to achieve a pregnancy within 12 months of regular
unprotected intercourse. It is classified as primary infertility if no previous pregnancies have occurred and
secondary infertility if it occurred after one or more pregnancies. Approximately 15% of couples
attempting their first pregnancy meet with a failure, and another 10% face secondary infertility. It has been
estimated that in about half of these couples a male factor is (co-)responsible. Thus, the causes of infertility
are grouped by sex and include male factors (35%), female factors (ovulatory dysfunction – 20%, tubal
dysfunction – 30%, abnormal cervical mucous – 5%), and those of unknown etiology (10%).
Hormonal imbalance has been proposed as a common reason for infertility. Hormonal aberrations may
result from problems with certain endocrine glands, such as the pituitary, thyroid, adrenal gland or ovaries.
In female it often leads to the inability to ovulate, or release, an egg and in men it can lead to infertility by
affecting the sperm – its development, shape, movement or quantity. This issue of Innersense highlights the
importance of proper endocrinological work-up in the evaluation of patients with infertility.
Male Factor
Approximately half of infertility issues are attributable to male factors. A
number of different factors may result in similar reductions of sperm count or
motility and affect sperm morphology.
Because of complex and incomplete knowledge of the underlying causes,
most infertile men are described as  Azoospermic: No sperm in the semen
 Oligozoospermic: A low number of sperm in the semen (low sperm count)
 Asthenozoospermic: Sperm have poor or low motility
 Teratozoospermic: Sperm have abnormal morphology
Male fertility depends upon an intact hypothalamopituitary-testicular axis to
initiate and maintain quantitatively and qualitatively normal spermatogenesis, maintain normal secondary
sex glands functions and sexual functions. Gonadotropin-releasing hormone (GnRH), luteinizing hormone
(LH), follicle stimulating hormone (FSH) and testosterone are very instrumental in overall
spermatogenesis.
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GnRH acts on the pituitary to stimulate secretion of LH and FSH
FSH plays an important role for the initiation and maintenance of spermatogenesis
LH plays a role in modulating testicular Leydig cell differentiation and steroidogenesis
Testosterone and its metabolite, dihydrotestosterone, are the principle male sex hormones
Inhibin B regulate testicular volume, sperm count, and sperm motility
Ovulatory Factor: Assessment of Ovulatory Function and Ovarian Reserve
Ovulatory dysfunction is observed in approximately 20% of all infertile women. Ovarian function is
expressed as follicular development, oocyte maturation and ovulation. A range of peptide and steroid
hormones regulate normal ovarian function, key members include the gonadotrophins (FSH & LH) and the
ovarian steroids (oestradiol & progesterone). Other known factors, such as Inhibin B and AMH are also
important.
Dec 21, 2010
Voice 114
Causes of ovulatory dysfunction include –
 Polycystic ovary disease – characterized by
excessive androgen production by either the
adrenals or the ovaries, which become enlarged
and contain multiple cysts.
 Hyperprolactinemia – Hyperprolactinaemia is
associated
with
reduced
secretion
of
gonadotrophins and hence anovulation.
 Hypothalamic anovulation – ovulation is
dependent on the presence of a functioning
hypothalamic-pituitary-gonadal axis, any alteration
in the GnRH pulse generator alters gonadotropin secretion & eventual response at the level of the ovary.
 Premature ovarian failure (POF) – Premature ovarian failure is a primary ovarian defect characterized
by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of
40 years (secondary amenorrhea). It is defined by abnormally low levels of estrogen and high levels of
FSH, much before the age of onset of menaupasue, which demonstrate that the ovaries are no longer
responding to circulating FSH by producing estrogen and developing fertile eggs.
FSH, LH& Prolactin
 The presence of elevated LH/FSH concentrations with a decreased estradiol concentration is diagnostic
of hypergonadotrophic hypogonadism
 The co-existence of decreased LH, FSH and estradiol values is diagnostic of hypogonadotrophic
hypogonadism
 Increasing levels of prolactin can cause a woman to progress from a deficient luteal phase to overt
amenorrhea, usually associated with complete GnRH suppression.
 Low progesterone levels, often called Luteal Phase Defect (LPD) implicates poor follicular phase oocyte
development
Inhibin B
 An important indicator of Ovarian Reserve (the ovary's capacity to respond to gonadotropin stimulation)
 Predicts Magnitude of Retrievals
 Used to determine Ovarian Hyperstimulation Syndrome (OHSS)
 Determines Gonadotropin Dosage for Assisted Reproductive Technology
Anti-Mullerian hormone (AMH)
 Serum AMH levels is a good marker for the quantitative aspect of
ovarian reserve.
 AMH levels are strongly correlated with the size of the follicle
pool.
 AMH levels do not change significantly over the course of the
menstrual cycle.
 Serum AMH level can also serve as a marker in ovarian
pathophysiology, such as polycystic ovary syndrome (PCOS).
Note: For more details on AMH please refer to Jan’ 09 issue of our Medimail
Evaluation of Infertility
Evaluation is the starting point for treatment of infertility as it may
suggest specific causes and appropriate treatment modalities.
Although the history and physical examination provide important
information, specific diagnostic tests are required to evaluate
infertility. Because the causes of infertility can be multifactorial, a
Dec 21, 2010
Voice 114
systematic approach typically is used and involves testing for male factor, ovulatory factor, uterotubal
factor, and peritoneal factor.
Endocrine Pre-analytical Issues
Specimen collection is a factor that must be considered to achieve appropriate test results. Many hormones
are released in a pulsatile fashion. In some cases, these spikes can be exaggerated by stress. Hence pooled
collection of samples is recommended.
Tests offered at SRL
Test Name
Sample
Test Code
Serum
(Age+ Sex+ Clinical History required) **Draw
Sample Between 8AM to 10AM, after 3-4 hrs patient
has awakened.**
Serum
(Age+ Sex+ sLMP + Clinical History required) **
Draw Sample Between 8 AM to 10AM, after 3-4 hrs
patient has awakened.**
Fasting Serum +Plasma Flouride+ Urine And
Post Prandial Serum +Plasma Flouride+ Urine
1577
Serum
(Age+ Sex to be mentioned+ Clinical History
1010
Serum
DT8100
Serum + Clinical History
1013
Serum ( Age+ Sex+ LMP + Clinical History
required)
2020
Serum
(Age+ Sex+ LMP + Clinical History required) **
Draw Sample Between 8 AM to 10AM, after 3-4 hrs
patient has awakened.**
Serum
2021
Dihydrotestosterone (DHT)
Serum
3151
AMH (Anti-Müllerian Hormone)
Serum
1705
Fertility Panel, Male, Endocrine
(Testosterone Free & Total, LH, FSH,
Prolactin)
Fertility Panel, Female, Endocrine
(TSH3G UL, Prolactin, Progesterone,
Estradiol, LH, FSH)
PCOD Panel (LH, FSH, Prolactin,
Testosterone (Total & Free), Insulin
(Fasting & PP) Fasting & PP Sugar)
Hirsutism Evaluation Panel (DHEA,
Serum Testosterone (Total and Free),
LH, FSH, Sex Hormone Binding
Globulin, 17 hydroxyprogesterone)
Thyprobe (TSH3G UL, THG, TPO,
FT4)
Inhibin B,LH, FSH & Prolactin
FSH & LH
LH, FSH & Prolactin
Inhibin B
1578
1011
3339
References
1. D. Madhukar et al. Hormonal Treatment of Male Infertility: Promises and Pitfalls. Journal of Andrology
2009;30(2):95-112
2. Geidam A D et al. Hormonal profile of men investigated for infertility at the University of Maiduguri in northern
Nigeria. Singapore Med J 2008; 49(7): 538
3. The ESHRE Capri Workshop Group. Physiopathological determinants of human infertility. Human Reproduction
Update 2002; 8(5):435-447