Professional Documents
Culture Documents
INFERTILITY
Infertility
Infertility is defined as a failure to conceive within one or more
years of regular unprotected coitus
– Primary Infertility – patient’s who have never conceived
– Secondary Infertility – indicates previous pregnancy
but
failure to conceive subsequently’.
Defective spermatogenesis
Abnormal Semen Parameters
Obstruction of the duct
Failure to deposit sperm high in the vagina
Idiopathic
Varicocele
Hormonal
Systemic causes
Immunological
Treatment of Infertility
• Needs to be evidence – based
• UK – based RCOG and NICE have produced
exhaustive guidelines
• Expectant management – for infertile couples
with a good prognosis for spontaneous
pregnancy
• ART – valuable treatment option for selected
couples with a low probability of natural
conception
THE RATIONALE
• Number of oocytes available
( chance of fertilization )
• Steroid production
( chance of implantation )
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GnRH agonists in combination with hMG and/or
FSH (long, short or ultra short protocol)
Poor responders
OHSS
Premature LH surge
Multiple Pregnancy
Poor endometrial development
Empty follicle syndrome
Premature LH Surge
• Defined as a premature rise of LH > 10 IU / l
accompanied by a concomitant rise in progesterone
( > 1 µg / l – 3.2 Nm / l )
• Multifollicular recruitment during COH – sudden
increase in serum Estradiol levels ( E2 )
• Enough to induce a LH surge while follicular growth
is still in progress
• Seen in 20%(frydman) of cycles
• Detection- urinary or serum LH estimations
Premature LH surge
• Premature LH surge causes premature luteinization of
granulosa cells and progesterone production which
causes adverse effects on endometrium
• May result in cycle cancellation
• Impairs pregnancy rates
• Poor oocyte quality
• Decreased fertilization and implantation rate
• May interfere with adequate timing of IUI
• Economic and psychological stress for the patients
• Antagonist
History of GnRH analogs
• 1971: The GnRH decapeptide was isolated and its structure
elucidated
• Extensive work performed in the late 1970’s and early 1980’s
demonstrated the utility of LHRH super-agonists
• In 1980, pulsatile low-dose GnRH1a was used in a
physiological manner to produce the first reported pregnancy
in a woman with hypogonadotrophic hypogonadism
• 1982: The first demonstration that GnRH agonists can be used
to eliminate premature luteinization and control ovarian
stimulation
• 1991: The first report suggesting use of the GnRH antagonist,
Nal-Glue, to prevent premature LH rise and progesterone in
controlled ovarian hyperstimulation treatment.
• First establish pregnancy using recombinant FSH and GnRH
antagonist 1998
Gonadotropin Releasing Hormone
Analogs
– Agonists initially enhance Gonadotropin
released from the pituitary; but with
continuing administration, cause down-
regulation of the pituitary and reduced LH &
FSH secretion
– Antagonists bind onto GnRH receptors and
completely suppress the pituitary hormone
secretion within a few hours
GnRHa administered
FSH
GnRH antagonist
Cycle down Day of
Day 21-24 regulation hCG
2-4 weeks
GnRH agonist
FSH
Comparision of Mechanism of Action
• Rapid reversibility
• Slow reversibility
Clinical use of GnRH antagonists
• COH in infertility (IVF, IUI)
• Gynecological disorders
– Fibroids
– Endometriosis
– PCOD
• Antitumour activity
– Prostrate cancer
– Benign Prostatic Hyperplasia (BPH)
• Gynecological cancers
• Precocious puberty
• Hormonal male contraception
???? GnRH Antagonists and
tumour
• GnRH receptors ( and GnRH antagonist
effect) demonstrated in human malignant
tumours, breast, ovary, endometrium and
prostate
• Inhibits the release of Insulin like growth
factor and cell growth
• Potential use in IVF, prior to chemotherapy
in women wishing to become pregnant in
the future.
Single vs Multiple dose
GnRH antagonist protocols
oocyte embryo
gonadotropin administration pick up transfer
in an individualized dosage
1st day
of menstruation
1st day
luteal phase support
of gonado-
tropins
oocyte embryo
gonadotropin administration pick up transfer
in an individualized dosage
1st day
of menstruation
1st day
luteal phase support
of gonado-
tropins