INFERTILITY

Muluken G.
 Outline
Definition of infertility
– Primary
– Secondary
Male factor infertility
– Causes
– Diagnosis
– Treatment
Female factor infertility
Assisted reproductive technology
 INFERTILITY
 Infertility is failure of a couple to conceive after 12
months of regular intercourse without use of
contraception in women <35 years of age; and after 6
months of regular intercourse without use of
contraception in women >35 years
Some clinicians use the term sub fertility to describe this
failure to conceive unless the couple has been proven to
be sterile
Sterility implies an intrinsic inability to achieve pregnancy
, where as infertility implies decrease in the ability to
conceive
 Cont’d.
Fecundablity, the probability of achieving a pregnancy in
one menstrual cycle
Fecundity is the probability of achieving a live birth within
a single cycle
Fecundablity of couples in a single menstrual cycle is 20-
25%
Based on this estimate 85% of apparently normal couples
will conceive within the first year of attempted conception
Patients who have not achieved pregnancy after 12
months have even lower fecund ability.
 Cont’d.
Infertility is a common condition with important
psychological, economic, demographic, and medical
implications
A unique medical condition because it involves a
couple, rather than a single individual
Infertility could be
Primary infertility – applies to those who have
never conceived
Secondary infertility – designate those have
conceived at some time in the past
 Cont’d.
Epidemiology
Global incidence 8 – 12 %
The incidence rise to 20 – 30 % in sub-Saharan Africa
Factors contributing to high prevalence in sub Saharan
Africa
STI
Unsafe abortions
Unhygienic obstetric practice
Female genital cutting
High prevalence of Tuberculosis
 Cont’d.
Etiology(Causes of infertility)
Female factor =40 %
Male factor =30%
Both =20%
Unexplained=10%
 Cont’d.
The basic investigations that should be performed
before starting any infertility treatment are
Semen analysis
Confirmation of ovulation
Assessing ovarian reserve for woman>35years
Documentation of tubal patency
 Cont’d.
Seminal analysis
Most important male fertility evaluation
Cheap and non invasive
Normal result exclude male factor infertility
Test should be done after 2-3 days abstinence
Condom shouldn’t be used for sample collection
It should be examined within 1 hr of collection
 Cont’d.
Normal parameters of sperm
analysis(WHO)
Volume – 2-5 ml
Total sperm count – >20
million/ml
Sperm motility of > 50%
Morphology > 50% normal(Strict
criteria>15%)
PH -7.2 -7.8
Of which sperm count & motility
are the most important factor
Physiology of spermatogenesis
The male reproductive tract consists of the testis,
epididymis, vas deferens, prostate, seminal vesicles,
ejaculatory duct and urethra
In the man, the hypothalamus and pituitary gland
should be normal for the spermatogenesis and
testosterone synthesis
The testes is the site of spermatogenesis and
testosterone synthesis
 Cont’d.
The epididymis is an important site for sperm
maturation and an essential part of the sperm
transport system
The vas deferens then transport sperm from the
epididymis to the urethra, where they are diluted
by secretions from the seminal vesicles and prostate
Finally, semen must be ejaculated
Abnormalities at any of these sites, particularly the
epididymis and vas deferens, can cause infertility
 Cont’d.
The semen released is a gelatinous mixture of spermatozoa
and seminal plasma; however, it thins out 20 to 30 minutes
after ejaculation by a process called liquefaction.
Liquefaction occurs secondary to the presence of
proteolytic enzymes within the prostatic fluid.
The released spermatozoa are not usually capable of
fertilization.
Instead, a series of complex biochemical and electrical
events, termed capacitation, must take place within the
sperm's outer surface membrane before fertilization in the
cervical mucus
 Cont’d.
Finally, as part of fertilization, the sperm must undergo
the acrosome reaction, in which the release of enzymes of
the inner acrosomal membrane results in the breakdown
of the outer plasma membrane
The acrosome reaction and binding of sperm and ovum
surface proteins are important for the penetration of the
ovum's zona pellucida and subsequent fusion between the
ovum and sperm.
As the sperm penetrates the egg, it initiates a hardening
of the zona pellucida (cortical reaction), which prevents
penetration by additional sperm
 Causes of male infertility
 The causes of male infertility can be divided into four main
areas
1. Hypothalamic pituitary disease(hypogonadotropic
hypogonadism Pretesticular disorders)
Low level LH,FSH, testosterone
1 to 2%
Constitutional
Emotional stress
Malnutrition
Obesity
Tumors
 Cont’d.
2.Testicular disease(gonadal failure)
Hypergonadotropic hypogonadism
Elevated levels of LH and FSH with
low serum levels of testosterone
30 to 40%
Congenital or developmental
disorders
Undescended testicle
Genetic defects
Klinefelter syndrome(47xxy)
Acquired(e.g., radiation therapy,
chemotherapy, testicular torsion,
or mumps orchitis)
 Cont’d.
3 Post-testicular defects (disorders of sperm transport)
Normal level of FSH,LH,testestrone
10 to 20 %
Abnormalities of epididymis
Congenital absence of vas deference
Obstruction of vas deference
Sexual disorders
Impotence
Retrograde ejaculation
4 Idiopathic male infertility
40 to 50%
 Cont’d.
Semen analysis is the fundamental investigation for the
infertile man and directs the subsequent evaluation.
If routine semen analysis is abnormal, it should be repeated.
If repeated semen analyses demonstrate severe
oligozoospermia (<5 million spermatozoa/mL) or
Azoospermia, basal serum FSH, LH, and testosterone should
be measured
If serum concentrations of FSH, LH, and testosterone are
normal the problem is post testicular
A post-ejaculatory urine sample to examine for spermatozoa will
provide evidence about retrograde ejaculation if sperm are seen in
the urine.
 Cont’d.
If spermatozoa are not present in the post
ejaculatory urine, the man has obstructive
Azoospermia
In the absence of the vas deferens there will be
low seminal fluid volume and acidic pH
If FSH,LH is elevated with low level of
testosterone the problem is testicular
If FSH, LH, testosterone are low the problem is
Pretesticular
 Cont’d.
• Treatment of male factor infertility
Treatment depends on the specific cause
General
Emotional support & assurance
Avoid smoking, alcohol, chat
correction of psychological problems
Maintain BMI at 20-24
 Cont’d.
– For hypothalmo pituitary dysfunction(hypogonadotropic
hypogonadism )
• Hormonal treatment is effective
– pulsatile gonadotropin–releasing hormone (GnRH)
therapy is effective
– For post testicular Azoospermia
– Micro surgery to correct the obstruction
– Surgical Sperm Recovery for Intracytoplasmic Sperm
Injection(ART)
– For gonadal failure
– Donor Insemination may be used(ART)
 Cont’d.
• For severe sexual dysfunction and retrograde
ejaculation
Drugs
ART
 Cont’d.
If the semen analysis is normal, the female partner
should be thoroughly investigated
After detail history and thorough physical
examination
Investigation of female infertility should be started
with
Confirmation of ovulation
Assessing ovarian reserve for those women>35years
Documentation of tubal patency
 Ovulation Physiology

At puberty there are 300,000 primordial follicles

Each month there is selection and growth of many
primordial follicles
Dominant follicle produces estradiol which leads to
LH surge
Ovulation occurs 36 hours after LH surge
Progesterone is increasingly produced after the LH
surge
Secretory changes to the endometrium occur
secondary to the increased progesterone levels
 Cont’d.
Assessment of Ovulatory function 
 Assessment of Ovulatory function is a key
component of the evaluation of the female
partner since
Ovulatory dysfunction is a common cause of
infertility(4o%)
The treatment of women with Ovulatory
dysfunction is aimed at improving or inducing
Ovulatory function
 Cont’d.
1. Clinical ways of assessing ovulation
By following pattern of basal Body Temperature
The least expensive method of confirming ovulation by
recording body temperature every morning
Thermogenic effect of progesterone increases body
temperature by at least 0.5 degree F. for at least 10days
Following the cervical mucus pattern(billings method)
Loss of fern pattern
Loss of spinbarkiet(strechablity of cervical mucus up to
10cm )
 Cont’d.
2.Mid-luteal phase serum progesterone level
Laboratory assessment of ovulation
Monitored one week before the expected menses.
For a typical 28-day cycle, the test would be
obtained on day 21
A progesterone level >3 ng/mL is evidence of
ovulation
If the progesterone concentration is <3 ng/mL, the
patient is evaluated for causes of an ovulation.
 Cont’d.
3. urinary ovulation prediction kit
These kits detect luteinizing hormone (LH) and are
highly effective for predicting the timing of the LH
surge that reliably indicates ovulation
4. Serial ultrasound
To follow the development and ultimately the
disappearance of a follicle
5. Endometrial biopsy
To document secretory changes in the endometrium
Too expensive or invasive for routine use
 Cont’d.
Assessment of ovarian reserve 
The identification of diminished ovarian reserve is an
increasingly important part of the initial infertility
evaluation
For women over 35 years of age and younger women
with risk factors for premature ovarian failure
Day 3 FSH level
 Clomiphene citrate challenge test (CCCT)
Antral follicle count by ultrasound
Anti-müllerian hormone (AMH) level
 Cont’d.
Confirmation of tubal patency
– Obstruction of the fallopian tubes
• PID is the commonest cause
– 12% of women will be infertile after a single
episode of PID
• Congenital
• The initial diagnostic test used to assess tubal patency,
hysterosalpingography (HSG)
• Has a sensitivity of 85% to 100% in identifying tubal
occlusion.
HSG: Tubal Infertility
 Female infertility
Common causes
An ovulation
Tubal obstruction
Uterine & cervical factors
 Cont’d.
Ovulatory factor
Is due to an ovulation
Cause Could be
Hypothalamus
Pituitary
Ovary
Gonadal dysgenesis
Premature ovarian failure
Ovarian failure due to chemotherapy, radiotherapy,
infections
polycystic ovarian syndrome
 Cont’d.
Tubal/Peritoneal Factor
Damage or obstruction of fallopian tube
Peritubal/periovarian adhesions
PID
Pelvic Surgery
Endometriosis
 Cont’d.
Uterine Factor
Congenital malformation
Endometrial polyps
Leiomyomas
Uterine synechiae - Asherman’s syndrome
 Cont’d.
Cervical Factor
Congenital elongation of Cervix
Uterine prolapse – 2o & above
Cervical polyp/ stenosis
Decreased amount of mucus
Conization
Antisperm antibodies
 Cont’d.
Vaginal Factors
Vaginal atresia (partial or complete)
Transverse vaginal septum
Systemic Diseases
Renal failure
Liver failure
Metastatic cancer
Unexplained
 Cont’d.
An ovulation / oligo –ovulation confirmed
Serum FSH
Prolactin
TSH
Serum Testosterone
 Treatment of female infertility
Treatment depends on the specific cause
General
Emotional support & assurance
Avoid smoking, alcohol, chat
correction of psychological problems
Maintain BMI at 20-24
 Cont’d.
Medical Diseases that will affect ovulation like
hypothyroidism & Hyperprolactinemia should be
treated accordingly
Abnormality in hypothalamus & pituitary
– pulsatile gonadotropin–releasing hormone
(GnRH) therapy can be used for disorders like
kallman syndrome ( idiopathic hypogonadothropic
hypogonadism in w/c there is deficiency of GnRH but normal
hypothalamic- pituitary function.)
 Cont’d.
• Ovulation induction
– Ovulation induction refers to the therapeutic restoration
of the release of one egg per cycle in a woman who
either has not been ovulating regularly or has not been
ovulating at all
– By chlomepine citrate
• A functional hypothalamic–pituitary–ovarian axis is
required
• Increases GnRH pulse amplitude
• Increases gonadotropin release from pituitary
 Cont’d.
• Super ovulation is indicated for the
treatment of unexplained infertility in
women who have been unable to conceive
despite regular, monthly ovulation.
• The explicit goal of super ovulation is to
cause more than one egg to be ovulated,
thereby increasing the probability of
conception.
 Cont’d.
• For ovarian failure(eg. Turner syndrome)
– Use of donor oocytes(ART)
• For those with no uterus and significant genital tract
abnormality(Mullerian agenesis)
– ART followed by Surrogacy of uterus
 Cont’d.
• Tubal factor
– Obstruction of the fallopian tubes
– Diagnosis will be confirmed by hysterosalpingogram
– Treatment
– Tuboplasty –surgical technique used to correct
tubal patency
– If the surgery fails assisted reproductive
technique is recommended
 Cont’d.
• Treatment of Unexplained Infertility
– Unexplained infertility is a diagnosis of exclusion
– 12-15% of infertile couples
– Chance of achieving pregnancy is very law
– Treatment:
• Clomiphene Citrate for super ovulation
followed by Intrauterine Insemination
ASSISTED REPRODUCTION TECHNOLOGY

These techniques have revolutionized the

management of infertile couples
All methods of ART, by definition, involve
interventions to retrieve oocytes(by super
ovulation)
These techniques include IVF, ICSI , cry preserved
embryo transfers, and the use of donor gametes
The take home baby rate is roughly around 20%
 Cont’d.
• The mandate of the ART team is to attempt to recreate precisely
those processes known to occur in unassisted conception.
• In all ART procedures, male gametes are initially collected directly
by ejaculation into a sterile cup.
• They are then processed, concentrated ,and incubated in protein–
supplemented media for 3 to 4 hours before being used for
fertilization.
• This final incubation allows for sperm capacitation.
• Before fertilization, retrieved oocytes also are cultured in protein–
supplemented media for about 6 to 8 hours.
• For IVF purposes, 50,000 to 100,000 capacitated sperm are placed
in culture with a single oocyte
 Cont’d.

• In vitro fertilization
(IVF) and embryo
transfer
 Cont’d.
• Intracytoplasmic Sperm Injection
– This micromanipulation technique is performed to increase
the fertilization rate of oocytes retrieved during ART by
direct injection of a live sperm into the oocyte, thereby
theoretically bypassing limitations imposed by sperm
motility, defective capacitation or acrosome reaction, and
sperm binding the zona pellucida.
– Some couples with male factor infertility do not achieve
pregnancy with artificial insemination, whereas others have
initial semen parameters that make insemination a
suboptimal approach are indications to consider this type of
ART
 Cont’d.
• Complications
– Higher order pregnancy
– Ovarian hyper stimulation syndrome (OHSS)
– Low birth weight
– Abortion
– Birth defects
– Ectopic pregnancy
 Cont’d.
• Multiple gestation, especially higher–order
multiple gestation, is a serious complication
of infertility treatment and has tremendous
medical, psychological, social, and financial
implications
• May reach up to 30%
 Cont’d.
• The incidence of ectopic pregnancy is 1% in
the general population however, its
incidence is increased after ART and can be
as high as 4%
• The incidence of heterotopic pregnancy,
which is normally rare, is particularly high
(1%) after ART treatment.
 Cont’d.
Ovarian hyper stimulation syndrome is a medical complication
that is both completely iatrogenic and unique to the treatment
of infertility
Although the pathophysiology of OHSS is not well understood,
the increased production of vasoactive substances—such as
renin, angiotensin–converting enzyme, angiotensin I,
angiotensin II by the hyper stimulated ovaries has been
implicated
The signs and symptoms of this disease can be attributed to
local and systemic increase in capillary permeability.
These changes, in turn, result in the depletion of intravascular
volume at the expense of third–space fluid accumulation
 Cont’d.
• Adoption should also
be considered as an
option of management
of infertile couples
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