male and female infertility

INFERTILITY
PRESENTER : DR SREELASYA
SRI SIDDHARTHA MEDICAL COLLEGE AND RESEARCH HOSPITAL,
TUMKUR

• Infertility :the inability of couples of reproductive age to establish a
pregnancy within 1 year through unprotected sexual intercourse.
• Primary: in which no previous pregnancies have occurred
• Secondary infertility : in which a prior pregnancy, although not a live
birth has occurred.
• About 90% of couple should conceive in 12 months of unprotected
intercourse.

• Fecundability - probability of pregnancy per cycle which may be 20%
in fertile couples.
• Fecundity - probability of achieving a live birth in a single cycle.

CAUSES
• Causes
Male causes 35%
Female
Tubal and pelvic pathology
Ovulatory dysfunction
50%
35%
15%
Unusual causes 5%
Unexplained causes 10%

SPERMATOGENESIS
• After migration of germ cells to genital ridge during embryogenesis,
there are approximately 3,000,000 spermatogonia in each gonad.
mitotic division
600 million in each testis

• Spermatogenic process is directed by genes located on Y
chromosome and takes approximately 70 days to complete from the
spermatocyte stage.
• 12-21 days are required for the transport of sperm from the testis
through the epididymis to the ejaculatory duct.
• During passage through epididymis, sperms mature further to
develop the capacity for sustained motility.
• Final maturation or capacitation of sperm may occur after ejaculation
into the female genital tract.

CAUSES OF MALE INFERTILITY
• HYPOTHALAMIC PITUITARY CAUSES
• Idiopathic isolated gonadotropin deficiency.
• Kallmann syndrome
• Single gene mutations
• Hypothalamic and pituitary tumours
• Infiltrative diseases
• Hyperprolactinemia
• Drugs
• Chronic systemic illness or malnutrition
• Infections
• Obesity

• Primary gonadal disorders
• Klinefelter syndrome
• Y chromosome deletions
• Single gene mutations and polymorphisms
• Cryproorchidism
• Varicocele
• Infections
• Drugs
• Radiation
• Environmental gonadotoxins
• Chronic illnesses

• Disorders of sperm transport
• Epididymal dysfunction or obstruction
• Congenital bilateral absence of the vas deferens
• Infections causing the obstruction of vas deferens
• Vasectomy
• Kartegeners syndrome
• Young syndrome
• Ejaculatory dysfunction

HYPOTHALAMIC PITUITARY CAUSES
Any hypothalamo pituitary disease or disorder causing a deficiency of GnRH can
cause male infertility.
The most common congenital cause is Idiopathic isolated gonadotropin deficiency.
Kallmann syndrome : when accompanied by one or more extra gonadal
abnormalities :
anosmia,
red-green colour blindness ,
midline facial defects like cleft plate,
neuro sensory hearing loss ,
synkinesis or
renal anomalies.

• Cause : mutation involving cell surface adhesion molecules or
receptors which are required for migration of GnRH neurons rom
olfactory placode to the hypothalamus , eg: KAL1,FGF,PROK2,

Hypothalamic and pituitary tumours
• eg : craniopharyngioma , macroadenoma
• Can distort the pituitary stalk or compress and suppress pituitary
gonadotropes.

INFILTRATIVE DISEASES
• Sarcoidosis
• Histiocytosis
• Hemochromatosis
• Inhibit GnRH or pituitary gonadotropin secretion.

DRUGS
• GnRH ANALOGUES
• Androgens
• Estrogen
• Glucocorticoids
• Opiates
• Cause hypogonadotropic hypogonadism

Primary gonadal disorders
Klinefelter syndrome
• Most common cause of primary testicular failure.
• 1 in 1000 males
• Characterized by sex chromosomal aneuploidy
• 47XXY
• Trinucleotide CAG repeats on the androgen receptor gene
• As the length of the repeat sequence increases, receptor activity
decreases.

• FSH, LH : elevated
• Testosterone : decreased
Presents as
• tall stature,
• length of arms and legs increased due to testosterone deficiency
• lower bone mineral density,
• gynecomastia,
• Decreased penile length,
• Small firm testis, resulting from damage to both seminiferous tubules and leydig cells.
• Cryptoorchidism is common in men with klinefelter syndrome
• Severely reduced sperm counts and are undervirilized.

• Psycho social abnormalities :
• Marked lack of insight
• Poor judgement
• Impaired ability to learn
• Speech and attention related disorders.
• Increased risk for pulmonary diseases, breast cancer, mediastinal
germ cell tumours, SLE, varicose veins, diabetes mellitus.

Y chromosome deletions
• 20% of men with infertility
• Yq11 ( azoospermic factor , AZF )
• AZFa, AZFb result in azoospermia
• AZFc : oligospermia to azoospermia

Single gene mutations and polymorphisms
• Normal male sexual differentiation and spermatogenesis require both
normal androgen production and normal androgen receptors.
• Androgen receptor plays an important role in the differentiation of
spermatids and their release from the seminiferous tubules.
• The number of trinucleotide CAG repeats in exon 1 of the androgen
receptor gene is inversely correlated to the transcriptional activity.

CRYPTOORCHIDISM
• Failure of testicular descent during fetal development.
• It is an Androgen dependent process.
• Unilateral or bilateral.
• Associated with impaired spermatogenesis
• Increased risk for testicular tumours,
• Serum FSH : elevated
• LH : normal
• Severity of the semen abnormality relates to duration of time the testis
have been outside of scrotum.

varicocele
• Dilation of pampiniform plexus of the spermatic veins in the scrotum.
• Common on left than right (because left spermatic vein is longer and
joins the left renal vein at a right angle.)
• Although increased testicular temperature delayed removal of local
toxins, hypoxia and stasis are viewed as mechanisms likely to be an
association between varicoceles and infertility , the causal
relationship has not been established.

Infections
• Mumps
• Tuberculosis
• Leprosy
• HIV

DRUGS
• Alkylating agents : cyclophosphamide chlorambucil
• Anti androgens : flutamide, cyproterone acetate
• Ketoconazole, cemitidine,
• Anabolic steroids
• Radiation : 0.01Gy can suppress spermatogenesis,
• >6 Gy : permanent azoospermia and infertility.

Disorders of sperm transport
Even when sperm production is normal, epididymal dysfunction or
obstruction can result in infertility.
• Congenital or acquired abnormalities of vas deferens can cause
obstruction and infertility
• 1-2% of infertile men have congenital bilateral absence of vas
deferens, (mutations of CFTR gene)
• Infections : gonorrhoea, chlamydia, tuberculosis
• Primary ciliary dyskinesia (kartageners syndrome)
• Young syndrome

• Ejaculatory dysfunction resulting from spinal cord injury or disease ,
sympathetomy or autonomic disease is another cause of infertility
relating to disrders of sperm transport

EVALUATION
• GOALS :
• To identify and to correct specific causes of infertility , when possible
• To identify individuals whose infertility cannot be corrected but may
be overcome by IUI or use of various forms of ART.
• To identify individuals having a genetic abnormality that may affect
the health of any offspring that may be conceived through the use of
ART.

• To identify individuals whose infertility can neither be corrected nor
overcome with ART, for whom adoption or the use of donor sperm
are options worthy of consideration.
• To identify any important underlying medical condition that may
require specific medical attention

• Evaluation of male partner should begin at the same time as female
partner , generally when pregnancy fails to occur in 1 year of
reasonably regular unprotected intercourse.
• Earlier evaluation is indicated for men with any obvious infertility risk
factor, those whose partner is ≥ 35 years, and men who have reason
to question their fertility.

HISTORY
• Duration of infertility and previous fertility.
• Coital frequency and any sexual dysfunction
• Results of any previous evaluation or treatment for infertility
• Childhood illnesses and development history
• Previous surgery
• Past episodes of or exposure to sexually transmitted infections
• Exposure to environmental toxins, including heat
• Current medications and allergies
• Occupation and use of tobacco, alcohol, other drugs.

PHYSICAL EXAMINATION
• Examination of penis to include the location of urethral meatus
• Palpation of testis and measurement of their size.
• The presence & consistency of both the casa and epididymis
• Secondary sexual characteristics including body habitus, hair
distribution , and breast development.
• Digital rectal examination.

SEMEN ANALYSIS
• IF A male infertility factor exists, it almost always will be revealed by
an abnormal semen analysis, although other male factors may be
involved even when semen quality is normal.
• Initial evaluation of male factor infertility should include atleast 1
properly performed semen analysis.
• If abnormal, another semen analysis should be obtained after atleast
4 weeks.

Instructions for semen collection
• Defined abstinence of 2-3 days
• Semen specimen should ideally be collected by
• masturbation directly into a wide mouthed clean container.
• If necessary , may be collected using silastic condom that does not contain spermicidal agents.
• Coitus interruptus.
• Can be collected within or near laboratory.
• When necessary , can be collected at home but should be kept at room
temperature or body temperature during transport.
• Regardless of the method of collection, semen sample should be examined
with in 1 hour after collection.

Normal reference values
Volume 1.5-5.0 ml
PH >7.2
Viscosity <3
Sperm concentration >20 million/Ml
Total sperm number >40 million/ejaculate
Percent motility >50%
Forward progression >2
Normal morphology > 50%
Round cells <5 million/Ml
Sperm agglutination <2

• In 2010, WHO published lower reference limits for semen analysis,
which represent 5th centile in population of over 1900 men from 8
countries on 3 continents whose partners conceived within 12
months.

lower reference limits
Volume 1.5(1.4-1.7) ml
Sperm concentration 15(12-16)million/Ml
Total sperm number 39(33-46) million/ejaculate
Total motility 40 (38-42)%
progressive motility 32(31-34)%
Normal morphology 4 (3-4)%
Vitality 58(55-63)%

EJACULATE VOLUME & pH
• Majority of semen volume comes from the seminal vesicles which
share a common embryology with vas deferens.
• Low or absent ejaculate volume suggests
• Possibility of failed emission
• Short abstinence interval
• Congenital bilateral absence of vas deferens
• Ejaculatory duct obstruction
• Hypogonadism
• Retrograde ejaculation

• Post ejaculatory urinalysis can detect retrograde ejaculation and
should be considered whenever the ejaculate volume is < 1ml except
when hypoganadism , CBAVD, collection problems, or shorter
abstinence intervals offers an obvious evaluation
• When indicated, post ejaculatory urinalysis involves centrifugation for
10 min at no < 300 g, followed by microscopic examination of the
pellet.
• In men with no or low semen volume and azoospermia , observation
of any sperm suggests retrograde ejaculation.

Sperm concentration and total sperm count
• Azoospermia : absence of sperm on standard microscopic
examination
• Prevalence : 1% in all men
• 10-15% in infertile men
• To establish the diagnosis, semen should be centrifuged at high speed
(3000g for 15 min ) and the pellet must be examined at high
magnification(400X)
• Absence of sperm should be documented on atleast 2 separate
occasions.

Classification of azoospermia
• Obstructive :
• NORMAL SPERM PRODUCTION.
• blockage anywhere in ductal system, from efferent ductules to the
ejaculatory ducts,
• CAUSES :
• Infections,
• iatrogenic injury during scrotal or inguinal surgery
• Congenital anomalies (CBAVD)
• APPROXIMATELY 40% OF AZOOSPERMIC MEN HAVE AN OBSTRUCTION.

• NON OBSTRUCTIVE:
• Intrinsic testicular disease(primary testicular failure)
• Endocrinopathies
• Secondary testicular failure
• low level sperm production

Sperm motility , forward progression, total
motile count, vitality
• Sperm motility is estimated as a percentage of total sperm population
exhibiting any motion.
• Grades :
• Rapid (grade3-4)
• Slow (grade2)
• Non progressive motility (grade0-1)
• Probability of conception rises with increasing motility upto
approximately60%

• Decreased sperm motility is termed asthenospermia.
• In general , poor sperm motility (asthenospermia) suggests testicular
or epididymal dysfunction.
• May be associated with antisperm antibodies, genital tract infections,
partial obstruction of the ejaculatory ducts or at the site of a
vasectomy reversal , varicocele.

• Sperm vitality test can differentiate viable sperm from dead
• One method : mixing fresh semen with a supravital dye , sperm with
intact membrane function do not take up the stain.
• Another method: hypoosmotic swelling test
• Involves incubation of sperm in a hypo osmotic solution , tails of
sperm with a normal membrane function swell and coil as fluid is
transported across the membrane.

Sperm morphology
• Reflects the quality of spermatogenesis.
• Fertilization rates were highest when percentage of normal sperm :
14% or higher
• Very poor (7-8%) when less than 4% of sperm had normal
morphology
• Intermediate when values between these two values.

Specialized tests
• Sperm auto antibodies :
• Blood testis barrier normally isolates sperm form immune recognition
but if its disrupted and sperm is exposed to blood, an antigenic
response may result .
• Risk factors : ductal obstruction, previous genital tract infection,
testicular torsion, or trauma, or sterilization reversal .
• Important because they bind to sperm and interfere with the mobility
and there by fertilization.

• The widely used tests for the detection of sperm autoantibodies
involves the use of latex particles with attached antibodies on the
surface of sperm.
• Considered clinically important when more than 50% are coated,

Sperm penetration assay
• Zona pellucida surrounding the oocyte blocks the entry of more than 1 sperm and
fertilization by sperm.
• Here, zona free eggs collected from super ovulated hamsters are incubated with
washed human sperm and proportion of eggs penetrated or the number of
sperm penetration per egg by the sperm of the test subject is compared to that
observed in a parallel incubation using sperm from a known fertile individual.
• In theory, the test evaluates 4 specific sperm functions:
• Capacitation, the acrosome reaction, fusion with the oolemma, and
decondensation within the egg cytoplasm.

Human zona binding assay
• Uses bisected zona derived from human oocytes, not previously
exposed to sperm an compares the binding of the test subjects and
fertile control sperm .
• Limited availability of human zonae an the technical aspects of the
test effectively preclude application beyond use as an investigating
tool.

Acrosome reaction
• The acrosome is a membrane bound structure locate at the tip of the
sperm head containing proteolytic enzymes necessary for penetration
of the zona pellucida and acrosin is one of those enzymes.
• Acrosome reaction involves the fusion of the acrosome and the
plasma membrane, followed by release of the acrosomal enzymes
and exposure of the sperm head , which must occur after sperm
binding to the zona pellucida

• Sperm of infertile men exhibit an increased prevalence of
spontaneous acrosome loss and decreased acrosome reactivity in
response to treatment with a calcium ionophore.
• The clinical relevance of acrosin measurements and abnormal
acrosome reactivity invitro remains to be established.

Biochemical tests
• Sperm creatine phosphokinase
• Reactive oxygen species
• Sperm creatine phosphokinase is an important enzyme involved in
the generation ,transport and the use of energy within the sperm.
• In both fertile and infertile men, leucocytes are the principle source of
reactive oxygen species but sperm themselves also produce them.
• Chemiluminesecent probes may be used.

Endocrine evaluation
• Indications :
• Abnormal semen analysis(particularly a sperm concentration <10
million/ml)
• Sexual dysfunction(decreased libido, impotence)
Includes measurement of serum FSH,
Total testosterone levels

• Levels of FSH , LH, Testosterone helps to differentiate the clinical condition,
• In men with hypogonadotropic hypogonadism, generally all 3 hormone
levels are distinctly low.
• In men with abnormal spermatogenesis, the FSH level may be normal or
high, and LH and Testosterone are normal.
• With testicular failure, exhibit, high levels of FSH and LH and low or normal
testosterone concentration.
• With prolactin secreting pituitary tumour, have normal or low
gonadotropin concentration , low serum testosterone and elevated
prolactin level.

UROLOGIC EVALUATION
• Grossly abnormal SEMEN parameters are indication for a thorough
physical examination by a urologist or other specialist in male
reproduction .
• Transrectal ultrasonography
• Transscrotal ultrasonography
• Renal ultrasonography
• Testis biopsy.

Testicular Biopsy
• Evaluation of a severely oligospermic or azoospermic male may
include either open or percutaneous testicular biopsy to determine
whether viable sperm are present in the seminiferous tubules
(Sharlip, 2002).
• For example, even men with testicular failure diagnosed by elevated
serum FSH levels may have adequate sperm on biopsy for use in
intracytoplasmic sperm injection.
• The biopsy specimen can be cryopreserved for future extraction of
sperm during an IVF cycle.
• Thus, the biopsy may have diagnostic, prognostic, and therapeutic
value.

GENETIC EVALUATION
• Genetic abnormalities may cause infertility by interferrng with sperm
production or transport.
• Currently those most relevant to male infertility and its treatment
include mutations within the cystic fibrosis transmembrane
conductance regulator (CFTR)gene
• And are highly associated with CBAVD.
• Chromosomal abnormalities resulting in testicular dysfunction
(klinefelter syndrome,)
• Y chromosome microdeletions associated with abnormalities of
spermatogenesis.

•In the United States, 7.3 million women (12% of women of
reproductive age) had difficulty or were unable to get pregnant or
carry a baby to term.

Arlene J. Morales, M.D., FACOG
There Are Multiple Causes of Infertility
14%
6%
6%
7%
1%
6%
11%
13%
18%
19%
Causes of Infertility
Centers for Disease Control and Prevention. 2006 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic
Reports. 2008. http://www.cdc.gov/ART/ART2006/508PDF/2006ART.pdf. Accessed April 20, 2009.
Tubal factor
Ovaluatory dysfunction
Diminished ovarian reserve
Endometriosis
Uterine factor
Male factor
Other causes
Unexplained
Multiple factors
(female only)
Multiple factors
(male + female)

•Over the past few decades, postponement of childbearing has led to a
decrease in family size and increased rates of age-related female
subfertility.
•Age-related decreases in ovarian follicle numbers and a decay in oocyte
quality dictate the occurrence of natural loss of fertility and, ultimately,
menopause.
–Fixed early in life: primordial germ cells arrive in the gonadal ridge
by the seventh week of gestation.
–Total germ cell number peaks at 20 weeks of gestation!
–From a peak of 6-7 million, oocyte number declines to 350,000 by
birth.
–By puberty, there are 200,000 follicles remaining in the ovary.
–Menopause sets in at an average age of 51 years, although the rate
of the ovarian aging process is highly variable.

Determinants of Declining Fertility
With Advancing Age in Women
• Declining oocyte number and ovulatory disturbances
• Declining oocyte quality and increasing chromosomal and genetic mutations
• Luteal phase dysfunction
• Impaired fertilization rates
• Implantation failures
• Poor-quality embryos and genetic abnormalities
• Impaired endometrial receptivity

• Higher incidence of age-related gynecologic problems, including uterine
fibroids and polyps
• Declining sexuality
• Increased pregnancy wastage
• Early implantation failures and preclinical losses
• Clinical losses
• Increased incidence of general medical problems accompanying aging (eg,
type 2 diabetes mellitus, hypertension)
• High incidence of obstetric complications and poor
pregnancy outcomes

OVARIAN RESERVE
• Refers to the size of the non growing, or resting , primordial follicle
population in ovaries.
• It presumably determines the number of growing follicles and the quality
or reproductive potential of their oocytes.
• The tests appear to be better suited for determining how the ovaries will
respond to pharmacologic doses of exogenous gonadotropins in terms of
 follicle count ,
 the number of oocytes produced,
 serum estradiol levels during stimulation ,
 duration of stimulation, and the quantity of gonatropins required in a given
cycle.

• However unlike age, the results of ovarian reserve testing are poorly
predictive of pregnancy outcomes.
• These tests appear to be more indicative of oocyte quantity rather
than quality.
• Include both biochemical and ultrasonographic measures of the size
and the quality of the ovarian follicular pool.

• Biochemical tests :
• Basal measurements : S.FSH
• S.Estradiol,
• Inhibin B
• Antimullerian hormone
• Provocative tests :
• Clomiphene citrate challenge tests
• Ultrasonographic measures :
• Antral follicular count,
• Ovarian reserve volume

Follicular stimulating hormone
• Vary significantly across the cycle.
• Best obtained in early follicular phase(D2-4)
• Vary with the assay method
• WHO Second international reference preparation is used as the
standard.

Serum estradiol
• Basal Serum estradiol concentration by itself has little value as an
ovarian reserve test, but can provide additional information that
helps in the interpretation of the basal FSH level
• An early elevation in serum estradiol reflects advanced follicular
development and early selection of a dominant follicle, and will
suppress FSH concentrations.
• Thereby masking an otherwise obviously high FSH levels indicating
diminished ovarian reserve.

• When the basal FSH is normal and the estradiol concentration is
elevated (>60-80pg/ml), the likelihood of poor response to
stimulation is increased and the chance for pregnancy is decreased.
• When both FSH and estradiol levels are elevated , ovarian response to
stimulation is likely to be very poor.

Inhibin B
• Secreted primarily during follicular phase by the granular cells of
smaller antral follicles .
• Serum inhibin levels increase in response to exogenous GnRH.
• Gives some information regarding ovarian reserve.
• Has relatively low PPV (19-22%) but a relatively high NPV.

Antimullerian hormone
• Produced by granulosa cells of preantral and small antral follicles,
beginning when primordial follicles start development and ending
when they reach a diameter of 2-6mm
• Small antral follicles are likely the primary source because they
contain larger number of granulosa cells and a more developed
microvasculature.
• Number of small antral follicles correlate with the sicze of the residual
follicular pool and AMH levels decline progressively , becoming
undetectable near menopause

Clomiphene citrate challenge test
• Is a provocative and possibly more sensitive test of ovarian reserve
that probes the endocrine dynamics of the cycle under both the basal
and stimulated conditions.
• Clomiphene citrate is a nonsteroidal estrogen receptor modulator.
Although the exact mechanism is not fully understood, clomiphene is
believed to block the negative feedback inhibition of endogenous
estrogens on FSH secretion.

• With the test, a woman takes 100 mg of clomiphene citrate orally on
cycle day numbers 5 through 9.
• Estradiol and FSH levels are measured on day 3, and an FSH level is
measured on day 10.
• Follicle-stimulating hormone elevations at either time point are
indicative of diminished ovarian reserve.

Ovulatory Factor
• Ovulatory Factor
• Disorders of ovulation account for about 30% to 40% of all cases of
female infertility.
• These disorders are generally among the most easily diagnosed and
most treatable causes of infertility.
• Women who have regular cycles and premenstrual symptoms, such as
premenstrual breast swelling and dysmenorrhea, almost invariably
have ovulatory cycles.
• Because ovulation is prerequisite to conception, ovulation must be
documented as part of the basic assessment of the infertile women.

• Methods to document ovulation :
• Basal body temperature
• Cervical mucus
• LH monitoring
• Midluteal serum progesterone
• Ultrasound monitoring
• Endometrial biopsy

Basal body temperature
• The least expensive method of confirming ovulation is for the patient to
record her temperature each morning on a basal body temperature (BBT)
chart.
• The oral or rectal temperature should be determined before the patient
arises, eats, or drinks.
• The principle behind temperature charting as a means to document
ovulation is based on the thermogenicity of progesterone.
• Significant progesterone secretion by the ovary generally occurs only after
ovulation.
• The secretion of progesterone causes a temperature increase of about
0.58°F over the baseline temperature of 97° to 98.8°F typically recorded
during the follicular phase of the menstrual cycle.

Cervical mucus
• The cervical glands secrete mucus that is normally thick and
impervious to sperm and ascending infections.
• High estrogen levels at midcycle change the characteristics of this
mucus, and it becomes thin and stretchy.
• Estrogen-primed cervical mucus filters out nonsperm components of
semen and forms channels that help direct sperm into the uterus.

• Midcycle mucus also creates a reservoir for sperm, allowing ongoing
release during the next 24 to 72 hours and extending the potential
time for fertilization.

Fern test
• Specimen of cervical mucus obtained by platinum loop or pipette is
spread on clean glass slide and allowed to dry.
• When viewed under low power microscope , during the estrogenic
phase , a characteristic pattern of fern formation is noted
• This ferning disappears after ovulation and if previously present , its
disappearance is presumptive evidence of corpus luteal activity.
• Ferning is due to the presence of sodium chloride in the mucus
secreted under estrogenic effect.

• Ovulation mucus has the property of great elasticity and will
withstand stretching up to 10 cm.
• This phenomenon is called spinbarkeit or the thread test.
• During the secretory phase, the cervical mucus becomes tenacious
and its viscosity increases so that it loses the property of spinbarkeit
and fractures when put under tension.
• This property is called tack.
• The observation of this change in the cervical mucus pattern In the
menstrual cycle is one more evidence of ovulation.

LH monitoring
• Documentation of the LH surge represents a remarkably
reproducible method of predicting ovulation. Ovulation occurs 34 to
36 hours after the onset of the LH surge and about 10 to 12 hours
after the LH peak .
• Commercially available kits for documenting the LH surge are generally
accurate, quick, convenient, and relatively inexpensive enzyme–linked
immunosorbent assays (ELISA) using 40 mIU/mL as the threshold for
detection
• The positive and negative predictive values of these kits have been
described to be 90% and 96%, respectively.

• A 100% correlation between urinary LH prediction of ovulation and
transvaginal ultrasound diagnosis of ovulation has further confirmed
the value of urine LH detection kits for home ovulation detection
• Still, this ELISA test cannot detect urinary LH in up to 5% to 10% of
women, probably either because of failed recognition by the antibody
used or because their peak urinary LH concentration does not rise
above the threshold set by the kit manufacturers.

Relative hormonal fluctuations in a normal,
ovulatory, 8 day menstrual cycle.

Midluteal serum progesterone
• Elevations in serum levels of progesterone constitute indirect evidence of
ovulation.
• When used to document ovulation, serum progesterone measurement
should coincide with peak progesterone secretion in the midluteal phase
(typically on days 21–23 of an ideal 28–day cycle).
• The lower limit of progesterone levels in the luteal phase varies among
laboratories, but a level above 3 ng/mL (10 nmol/L) typically confirms
ovulation.
• Although ovulatory levels are often considerably higher than 3 ng/mL, low
midluteal serum levels of progesterone are not necessarily diagnostic of
anovulation.

Ultrasound Monitoring
• Ovulation can also be documented by monitoring the development of a
dominant follicle by ultrasound until ovulation takes place.
• Ovulation is characterized both by a decrease in the size of a monitored
ovarian follicle and by the appearance of fluid in the cul de sac
• It most often occurs when follicular size reaches about 21 to 23 mm,
although it may occur with follicles as small as 17 mm or as large as 29 mm
• Because of the inconvenience and expense of serial measurements, routine
use of ultrasound for documenting ovulation is discouraged.
• Instead, its use should be confined to the monitoring of ovulation induction
or superovulation.

Endometrial biopsy
Consists of curetting small pieces of the endometrium from the uterus
with a small endometrial biopsy curette, preferably 1-2 days before the
onset of menstruation.
Secretory changes prove that the cycle has been ovulatory.
Corpus luteal phase defect can also be diagnosed by endometrial
biopsy which shows a lag of 2-3 days between the calendar and
histological dating of the specimen.
Now, it is taken only in suspected tubercular endometritis and the
tissue is subjected to PCR.

PATHOGENESIS of PCOS
INSULIN RESISTANCE
HYPERINSULINEMIA
THECA CELL
PROLIFERATION
HYPERANDROGENISM
PCOS

Oxidative Stress & Infertility

Tubal factor
• 25- 35 % of infertility
• Non infectious causes for tubal infertility inclue tubal endometriosis,
salpingitis isthmica nodosa, tubal polyps, tubal spasms, untratubal
mucous debris
• Incidence of tubal infertility has been reported to be 8, 19.5%, 40%
after 1,2,3 episodes of PID respectively.
• C.trachomatis, N.gonorrhoeae are common pathogens associated
with infertility.

hysterosalpingography
• The initial diagnostic test used to assess tubal patency,
hysterosalpingography (HSG) has a sensitivity of 85% to 100% in
identifying tubal occlusion.
• The specificity of HSG in identifying PID–related tubal occlusion
approaches 90%
• Bilateral tubal pathology documented on HSG is associated with
significantly reduced fecundity rates and warrants further evaluation
using falloposcopy, selective salpingography, or laparoscopy.

• HSG usually is performed between cycle days 7 and 12
• Patient is premedicated 30-60 min prior to the procedure with
ibuprofen or related medication .
• Lidocaine injected intracervically may provide further pain relief.
• With the patient in dorsal lithotomy position , either a metal cannula
or a balloon catheter is inserted through the cervix and past the
internal cervical os
• Contrast dye is injected under fluoroscopy to visualize uterine cavity ,
fallopian tube architecture, tubal patency.

• During menses, HSG should be avoided because there is increased
incidence of vascular intravasation caused by dilatation of periuterine
veins.
• Additionally, there is the theoretical risk of retrograde dispensation
of menstrual endometrium into the peritoneum with attendant risk of
infection and endometriosis.
• The risk of infectious sequelae after HSG is 0.3% to 1.3%;
• The procedure often causes uterine cramping; prophylaxis with a
nonsteroidal anti– inflammatory medication taken 30 minutes before
the procedure may minimize this discomfort

• Because there is a high prevalence of current or past chlamydial
infection among infertile women and complications of HSG
associated pelvic infection could further compromise fertility, it is
reasonable to prescribe antibiotic prophylaxis to patients scheduled
for HSG.
• A recommended prophylactic regimen consists of doxycycline, 100 mg
twice daily, beginning the day before HSG and continuing for 3 to 5
days.
• Other rare complications of HSG include cervical laceration, uterine
perforation, hemorrhage, vasovagal reaction, and allergic response to
the contrast dye.

Hydrosalpinges
Myoma
Normal HSG

Chlamydia serology
Laparoscopy
• The most thorough technique for diagnosing tubal and peritoneal
disease is
• laparoscopy. It allows visualization of all pelvic organs and permits
detection of intramural
• and subserosal uterine fibroids, peritubal and periovarian adhesions,
and endometriosis.
• Abnormal findings on HSG can be validated by direct visualization on
laparoscopy.

Chromopertubation
involves the transcervical installation of a dye, such as methylene blue
or indigo carmine.
Tubal patency is assessed by direct laparoscopic visualizationof the dye
extruding through the fimbrial openings of the tubes.
Unlike HSG, laparoscopy allows careful assessment of the external
architecture of the tubes and, in particular, visualization of the
fimbria. Identified abnormalities, including tubal obstruction, pelvic
adhesions, and endometriosis, can be treated at the time of
diagnosis..

• Falloposcopy allows the visual identification of tubal ostial spasm,
abnormal tubal mucosal patterns, and even intraluminal debris
causing tubal obstruction.
• sonohysterography with contrast media offers a much less invasive
method of diagnosing fallopian tubal obstruction while maintaining a
sensitivity and specificity similar to that of laparoscopic
chromotubation

Cervical and Immunologic Factors
• Postcoital Test
• Cervical factor is estimated to be a cause of infertility in no more than 5% of
infertile couples.
• The classic test for evaluation of the potential role of cervical factor in infertility
is the postcoital test (PCT).
• The PCT is designed to assess the quality of cervical mucus, the presence and
number of motile sperm in the female reproductive tract after coitus, and the
interaction between cervical mucus and sperm.
• The test does not yield sufficient information on sperm count, motility, or
morphology to allow assessment of semen quality.
• The PCT should be performed 1 to 2 days before the anticipated time of
ovulation because sufficient estrogenization of the cervical mucus is critical to the
interpretation of the results.

• Intercourse after 2 days of abstinence and about 2 to 12 hours before
the PCT should be sufficient for testing purposes. Inexpensive and
easily performed, PCT involve both gross assessment of the cervical
mucus and microscopic assessment of the sperm– mucus interaction.
• A small amount of cervical mucus is withdrawn by means of oval
forceps or via an angiocatheter syringe. Cervical mucus is assessed for
clarity and for spinnbarkeit (i. e., stretchability), with normal
estrogen–stimulated mucus stretching 8 to 10 cm when pulled from
the cervix.

• The mucus is placed on a glass slide and covered with a cover slip. A
small trail of mucus may be left to dry outside the cover slip so that
ferning can be assessed.
• Estrogenized mucus is clear and watery with a characteristic ferning
pattern, whereas progesterone results in mucus that is opaque, thick,
and lacking ferning.
• The presence of sperm, number per high–power field, and motility
are assessed by the examination of several microscopic fields.

Antisperm Antibodies
• Both men and women have the capability to mount a humoral response to
sperm.
• Either allogenic or autoimmune response could, in turn, adversely affect
fertility.
• Antisperm antibodies (ASA)are most commonly limited to immunoglobulin
G (IgG), IgM, and IgA isotypes, and each subclass has characteristic
anatomic localization.
• Systemically produced IgG molecules may be found in serum as well as in
cervical mucus and semen.
• Agglutinating antibodies of the IgA class are typically found in cervical
mucus and seminal plasma.

• Testicular trauma or torsion, occlusion of the vas deferens secondary
to childhood inguinal herniorrhaphy or cystic fibrosis, vasectomy
reversal, and genital tract infections have been suggested to elicit
antisperm antibody formation.
• Though ASA are present in up to 9% to 12.8% of infertile couples ,
they are also found in up to 2.5% of fertile men and 4% of fertile
women .
• These findings would indicate that these antibodies may contribute
to subfertility rather than result in absolute infertility.

Uterine Factors
• Uterine pathologies are the cause of infertility in as many as 15% of
couples seeking treatment (289) and are diagnosed in as many as 50% of
infertile patients
• Uterine abnormalities that have been implicated in infertility include
• Endometrial polyps,
• submucous fibroids,
• intrauterine adhesions,
• mullerian anomalies, prior
• exposure to diethylstilbestrol (DES),
• and possibly luteal phase defect.

Diagnostic Imaging for Uterine Pathology
• HYSTEROSCOPY
• GOLD STANDARD for uterine cavity evaluation because it allows direct
visualization.
• To optimize visualization of the endometrial cavity during
hysteroscopy, the procedure should be performed during the early–
to midfollicular phase of the cycle. This also minimizes the possibility
of pregnancy.
• Although excellent acceptance of diagnostic hysteroscopy using a 5–
mm scope without analgesia has been reported .
• patient tolerance of office hysteroscopy has been optimized by
advancements in pain–control medication regimens.
• The most important benefit to office hysteroscopy is the ability to
immediately treat most pathology that is encountered.

Hysteroscopy
Polyp
Septum
©Tim Peters and Company, Inc. Peapack, NJ 07977, USA.

Hysterosalpingogram
• It allows assessment of both tubal and intrauterine pathology
• It shows general configuration of the uterine cavity and indicates
endometrial lesions as filling defects or irregularities of the
intrauterine wall.
• Excessive contrast may lead to false negative findings, which may
account to 50% sensitivity of HSG compared to hysteroscopy for
endometrial polyps.
• Inability to discriminate air bubbles, mucus, debris from intracavitary
pathology may account for high false positive rate when compared to
hysteroscopy.

Hysterosalpingography (HSG)
©Tim Peters and Company, Inc. Peapack, NJ 07977, USA.

sonohysterography
• Synonym : saline infusion sonography
• Involves transcervical instillation of saline, often via balloon catheter
during TVS to distend the uterine cavity and delineate the
endometrium .
• Performed during the follicular phase of the cycle and anaesthesia
typically is not required.
• Compared to hysteroscopy , it has 100% sensitivity, specificity and
positive and negative predictive values for uterine polyps.

MRI
• Although , TVS, HSG, SIS and hysteroscopy may suggest congenital
uterine anomalies, pelvic MRI is considered the gold standard.
• Particularly useful for diagnosing rudimentary uterine horn.

Congenital Anomalies of the Uterus
• Congenital uterine anomalies may be associated with infertility,
spontaneous pregnancy loss in the first or second trimester, or late–
trimester pregnancy complications.
• In women with didelphic, unicornuate, and septate uteri, the rates of
spontaneous abortion and preterm delivery are highly increased at
25% to 38% and 25% to 47%, respectively

In Utero Exposure to Diethylstilbestrol
•
Exposure to DES in utero increases a woman's risk for congenital
reproductive tract malformations and obstetric complications,
including preterm labor and cervical incompetence.
• The most common malformation was the T–shaped uterus

Acquired Abnormalities of the Uterus
• Leiomyomas
• Endometrial Polyps
• Intrauterine Synechiae or Asherman Syndrome.

• A treatment should be based on the diagnosis through the findings
of clinical history and examination,duration of infertility and the
woman’s age and laboratory investigations ,

• Education
• Moderation in consumption of alcohol and avoidance of drug abuse
• Reduce heat,avoid hot bath,avoid strenous activities and occupation
in hot environmentand control obesity
• Correct endocrinopathies. Prompt attention to diabetes and thyroid
disorders
Management of male infertility

• Percutaneous embolization of varicocele is attempted ,damage to the
testicular artery and recurrance of varicocele
• Surgical correctionof undescended testes in childhood improves the
semen quality in 60-70% cases
• The obstruction in the vas by vasoepididymal anastomosis will restore
patency
Surgical

• Ephedrine 600mg orally 4times a day for 2 weeks or alpha adrenergic
drug like phenylephrine 2.5mg is tried in retrograde ejaculation
• Antibiotics . Doxycycline 100mg bd for 6 weeks is beneficial
• Role of oxidative stress
• Premature ejaculation.SSRI take 2 weeks to reach the therapeutic
level,but depaxetineworks within 1 hour,30-60mg is taken 1hr before
intercourse

• Hormones . Testosterone ,pituitary hormones and GnRH have all been
tried to improve spermatogenesis with variable results .

• hCG 10,0for 10 weeks improves testosterone secretion,and pregnancy
rate by 38%00 IU IM weekly
alternately 5000IU may be given twice a week
• Testosterone 25-50mg daily orally improves testiclar function. A
larger dose of 100-150mg daily suppresses spermatogenesis,after 3
monts course of treatment ,rebound phenomena occur with
improved spermatogenesis.
Hormone therapy

• Clomiphene -25mg daily for 25days followed by rest for days is given
cyclically for 3-6cycles. It is recommended in hypogonadal infertility
• hMG 150 IU thrice a week for 6 months is recommended in pituitary
inadequacy.
• GnRH is indicated in hypothalamic failure
• Tamoxifen 10mg daily for 6 months has been found effective in some
cases

• Dexamethasone 0.5mg daily or 50mg prednisone daily for 10 days
each cycle for 3 -6 months. About 25-40% pregnancy rate is observed
,through avascular necrosis of the head of the femur and osteopenia.
• Cyclosporin A 5-10mg/kg daily for 6months is better than
corticosteroids in T Cell suppression

• Sildenafil is used only in erectile function nd does not improve libido.
With 25-100mg orally 1 hr before intercourse,the effect lasts for 1-
2hrs . The drug is effective 50-80% cases
contraindicated in the following :
Retinitis pigmentosa,diabetic retinopathy,patient on antihypertensive
drugs and cardiac diseases

• Obstructive azoospermia requires vasogram to study the site and
nature of blockage. Vaso vasal anstomoses has been successful in few
cases
• The advantage of surgery over ICSI is that it is a onetime treatment
and cost effective ,if successful with permanent effect
• 5% males suffer from azoospermia
Management of azoospermia

• First described by Asch et al 1984
• Involves aspiration of oocytes following ovulation induction either
laproscopically or under ultrasound guidance transvaginally
• The oocytes 2 per tube are mixed with 50,000 sperms and transferred
to each ampullary portion of fallopin tube 4 cmfrom the fimbrial end
.volume transferred is 10-20micron
GIFT

• Unexplained infertility
• Failed infertility
• Failed IUI
• Male infertility
• Immunological factor in mal and cervix
• Donor semen required(rare)
Indications for GIFT

• Results are better with GIFT than IVF i.e, 45% success versus 15-20%
but success rate with IVF is improving
• Abortion rate of 10-15% ,ectopic pregnancy 7% and multiple
pregnancy 20-50% have been reported with GIFT

• This sophisticated expensive techniques are needed
for the following reasons
1. IVF or GIFT fails due to fertilization failure
2. Immunologically derived infertility
3. Sperm binds to zona pellucida but fails to penetrate
due to either spermal antibodies or antibodies to
zona pellucida
4. No or weak binding of sperm to zona.
5. Oligospermia and asthenospermia
Microassisted fertilization process in vitro

Intracytoplasmic sperm injection is a micromanipulation technique in
which sperm is directly injected into oocyte . It has the benefit of
overcoming problems with
• Sperm motility
• Defects in capacitation
• Defects in acrosome reaction
• Problems of sperm binding to zona pellucida
ICSI

• Severe oligospermia<5million sperms/ml
• Asthenospermia
• Antisperm antibodies
• Ejaculatory disorders
• Oocytes abnormalities like thick zona
Indications for ICSI

• Latest technology employed in azoospermia caused by blocked vas
• It can be done under LA,but testicular biopsy requires GA
Epididymal or testicular aspiration or biopsy

• An exciting breakthrough in the filed of male factor infertility and
micromanipulation is a process called round spermatid nucleus
injection(ROSNI)
What is in future???

• Patient counselling
• Lifestyle changes
• Treatment for the causes

• The easiest and most successful treatment options for infertility
related to cervical factors is artificial IUI in conjunction with ovulation
inducing agents.
• Low dose estrogen therapy may provide some benefit in cases of
successful attempts of IUI,IVF.
Treatment for cervical factors

• 8% pregnancy rate after natural cycle IUI
• IUI can be performed in a natural (unstimulated IUI) or
gonadotrophins(stimulated IUI)
• Rate increses by 5-10% in timulated cycles
• 85%achieved within the first four cycles of IUIs.
Artificial intrauterine insemination

• Artificial insemination can be of 2 types homologous and
heterologous
• Intrauterine insemination is the best studied and most widely
practiced of all the insemination techniques.
• It involves placement of about 0.3 to 0.5 mL of washed, processed,
and concentrated sperm into
the intrauterine cavity by transcervical catheterization.

• For women with tubal factor infertility, treatment options are
reconstructive surgery and IVF.
• IVF has become the treatment of choice for much or most tubal
factor infertility, particularly for couples with other infertility factors
or severe tubal disease.
• However,surgery remains an appropriate option in select
circumstances and for couples with ethical or religious objections or
financial restrictions that preclude IVF.
Tubal Surgery in the Era of ART

• Dense pelvic adhesions.
• Loss of fimbriae.
• Bilateral hydrosalpinx > 3 cm (see p. 171).
• Length of the reconstructed tube < 4 cm.
• Reversal done after 5 years of sterilization
operation.
• Presence of other factors for infertility.
Factors for Poor Outcome Following Tuboplasty

• Unexplained infertility
• Cervical factor
• Failure to concieve after ovulation induction
Treatment
• Immunological causes (antisperm antibodies)
• Endometriosis
• Male factor like retrograde ejaculation and ejaculatory failure
Indications IUI

• Surgical intervention involves lysis of uterine septae and uterine
synechiae,surgical treatment of uterine anomalies(bicornuate uterus
)
• Uterine synechiae and sepatae are corrected using hysteroscopy
• It is performed during early follicular phase
Treatment of uterine factors

• Intrauterine balloon is left for 7 days inside the uterine cavity to
prevent the recurance of adhesions
• 3 modalities which are commonly used for treatment of
myomas(conventional laprotomy,operative laproscopy and operative
hysteroscopy)

• About 0.2% of women who choose surgical tubal sterilization request
reversal procedures
• The success of tubal reanastomosis depends on the method of
sterilization, the site of anastomosis, and the presence of other infertility
factors.
• Pregnancy rates are lowest (49%) after the reversal of sterilization
procedures involving unipolar electrocautery.
• In contrast, postprocedure pregnancy rates rose to 67% when the
sterilization technique involved Fallope rings or spring–loaded clips and
75% when Pomeroy
tubal ligation was employed.
Treatment of tubal factors of infertility

• Final anastomosed tubal lengths of less than 4 cm are associated with
low pregnancy rates
• Pregnancy rates higher than 40% have been reported after
microsurgical fimbriectomy correction

• Distal obstruction: fimbrioplasty and neosalphingostomy
• Proximal obstruction:hysteroscopic or fluoroscopic tubal
cathetrization and tubocornual anastomosis by laprotomy
Surgical procedures for improving tubal
patency

• Treatment option is to begin with ovulation inducing drugs.
• Women with hyperprolactinemia should be treated with dopamine
agonist such as Bromocriptine.
• Anovulation is treated with various ovulation induction agents like
CC,hMG,hCG,recombinant FSH and LH.
Treatment of ovarian factors

• It is a SERM with both estrogen antagonist and agonist effect.
• It exert anti-estrogen effect by competing with the estrogen receptors at the level
of hypothalamus,pituitary and ovaries.
• CC also can be prescribed to the women with unexplained fertility problems.
• Standard dose of CC is 50mg PO once a day for 5 days,starting on the day 3-5 of
the menstrual cycle or after progestin induced bleeding.
• A follicle should develop to a diameter of 23-24mm before a spontaneous LH
surge occurs.
• Adverse effects are multiple pregnancy,thickening of cervical mucus,hot
flashes,scotomas,dryness of vagina,headache and ovarian hyperstimulation.
• Contraindiacation are ovarian cyst,pregnancy,liver disease,breast cancer.
Clomiphene Citrate

• Indicated for ovulation induction in patients with primary
amenorrhea or infertility who did not respond to CC.
• hMG contains 75U of FSH and 75U of LH per mL,and concentration
may vary in the range of 60-90units for FSH and LH in the range of 60-
120U.
• Adverse effects are multiple pregnancy,ectopic
pregnancy,miscarriages,ovarian torsion and rupture,ovarian
hyperstimulation syndrome.
Human Menopausal Gonadotropins

• Indicated for patients with hypothalamic dysfunction,especiallly those
who do not respond to CC.
• Drug is administered in pulsatile fashion 60-120mins IV or SC using a
delivery pump in the starting dose of 5 ug per pulse IV or 5-25 ug SC
• The administration of GnRH should be extended throughout the
luteal phase or should supplemented with the administration of
exogeneous hCG.
Gonadotropins Releasing Hormone

• It is iatrogenic condition that occurs in patients undergoing ovulation
induction with hMG,or controlled ovarian hyperstimulation for
assisted reproductive technologies.
• Incidence rate fluctuates from 0.1% to 30%.
• The pathophysiology is associated with massive extravascular
accumulation of fluid.This causes severe depletion of intavascular
volume resulting in dehydration,hemoconcentration and electrolyte
imbalance.
Ovarian Hyperstimulation syndrome

• Treatment options are CC,insulin sensitizing agents such as
glucophage and metformin,dietary changes and surgery.
• Primary treatment is weight loss through diet and exercise.
• The aim of treatment is to control hirsutism,to prevent endometrial
hyperplasia.
• Women with PCOS who want to conceive,CC is used with high success
rate.
Treatment of PCOS

• Women with PCOS having BMI within normal range who have not
responded to CC can be treated with gonadotropins.
Gonadotropins

OHSS
• Serious and potentially lifethreatening physiologic complication seen
in 20% pateints undergoing controlled ovarian hyperstimulation
• There is increased capillary permeability resulting in IVF shift tp 3rd
space compartment

OHSS
• Predictors of OHSS
1. Young and lean patients
2. Polycystic ovary disease
3. High serum estradiol >400pg/ml
4. Ultrasonography – PCO pattern of response to GnRH before
hMG,large number of follicles >15 with a high proportion of small
and intermediate size follciles,conception cycles particularly
multilple pregnancy

5.Doppler intravenous vascular resistance uing color and pulsed
doppler
6.OHSS in previous cycle

Classificaton of OHSS
• Mild OHSS
1. Grade 1-abdominal distension and discomfort
2. Grade 2-features of grade 1 plus nausea,vomiting and /or
diarrhea;ovaries are enlarged 5-12 cm
Moderate OHSS
3.Grade 3- features of mild OHSS plus ultrasonic evidence of ascites

• Severe OHSS
Grade 4-features of moderate OHSS plus clinical evidence of ascites and
/or hydrothorax and breathing difficulties
Grade 5-all the above plus change in the blood volume ,increased
blood viscosity due to hemoconcentration,coagulation abnormality
and diminished renal perfusion and function

• Navot et al proposed to define the secrest degree of
OHSS as a critical or lfe threatening stage. This
included cases of tense ascites,hydrothorax
Hematocrit>55%
White blood cells>25,000
Serum creatinine >1.6gm/dl
Creatinine clearance <50ml/min,thromboembolic
phenomena
Adult respiratory distress syndrome

• Mild manifestations are relatively common are include:
Transient lower abdominal discomfort
Mild nausea
Vomiting
Diarrhea
Abdominal distension

• Serious illness exists when pain is accompanies by one or more of the
following
1. Rapid weight gain
2. Tense ascites
3. Hemodynamic instability(orthostatic hypotension,tachycardia)
4. Respiratory difficulty
5. Progressive oliguria,laboratory abnormalities

Management of ohss
• Fluid therapy – rapid initial hydration may be accomplished with a
bolus of 500-1000ml normal saline
• Intravenous albumin-100ml of 20% solution at the rate of 50ml/hr
repeated at 4-12 hr intervals
• Strict input and output chart

Prevention of OHSS
• Withholding hCG±continuation of GnRH :most
common method
• Delaying hCG controlled drift method
• Follicular aspiration
• Progesterone for luteal support
• Cryopreservation and replacement of frozen thawed
embryos at a subsequent cycle
• Selective oocyte retrieval in spontaneous concepion
• Gradual and slow hMG step up protocol in PCOS
• Albumin at time of retrieval

• Reasons for poorer pregnancy outcomes in ART cycles
in PCOS:
1. Cytoplasmic and nuclear disparity in maturation
2. Higher incidence of unexplained failed fertilization
3. Higher incidence of failed oocyte recovery
4. High LH which can be treated with use of GnRH
agonists
5. Higher incidence of OHSS.

• Procedure involves creation of 4-20 holes having a size of 3mm
diameter and 3mm depth to be made in each ovary on
antimesenteric side
Laproscopic Ovarian Drilling

• It is a SERM
• It is used for secondary chemo prevention hormone responsive breast
cancer,for ovulation induction.
• It has lower anti-estrogenic effect on endometrium and cervix
compared to CC.
Tamoxifen Citrate

• They inhibit the action of enzyme aromatase which responsible for
the process of conversion of androgen to estrogen thereby estrogen
levels are reduced releasing hypothalamic pituitary axis from its
negative feedback.
• Eg:Letrazole and Anastrozole.
Aromatase Inhibitors

• Patient with PCOS with BMI more than 25 are resistant to CC
alone.These patients have other problems such as hyperinsulinism
and hyperandrogrnism associated with acanthosis nigricans.
• Metformin improves insulin sensitivity,decreases hepatic
gluconeogenesis,reduces hyperinsulinism,stimulate LH level and free
testosterone concentration.
• Adverse effects- gastrointestinal intolerance,nausea,vomiting and
abdominal cramps,weight loss.
• Dose-500mg PO once a day for 7 days,then 500mg BID for another 7
days and finally 500mg TID.
Metformin

• Surgical resection of endometriosis
• Ovulation induction plus IUI
• Assisted Reproductive technologies (IVF)
Treatment of Endometriosis

• Drugs such as anti-estrogen and IUI
• If none these option work then the treatment is IVF.
Treatment of Unexplained Infertility

In Vitro Fertilization
• It consist of retrieving a preovulatory oocyte from the ovary fertilizing
it with sperm in laboratory and subsequently transferring the embryo
within the endometrial cavity
Assisted Reproductive Technique

• Womens age (23-39 yrs)
• Number of embryos to be transferred (more the no. of embryos are
transferred more the chance of success)
• No. of previous treatment cycles (chance of coception decreases
after 3 cycles of IVF)
• Pregnancy History (treatment is more effective for womens are
previously been pregnant)
• Alcohol,Smoking and caffeine conception
• Body mass index (more BMI reduces success rate)
Factors affecting the outcome of In vitro fertilization

• Tubal factors for infertility like blocked tubes/impaired
tubal function,previous tubal ligation
• Endometriosis
• Male infertility
• Idiopathic infertility
• Immunologic infertility
• No conception after 3 IUI cycles
Indication

• For cryopreservation of embryos
• Surrogacy

• Ovarian stimulation
• Follicular aspiration
• Sperm preparation
• Oocyte incubation
• In vitro maturation
• Embryo culture
• Embryo Transfer
Procedure

• Indication
• obstructive azoospermia
• Non obstructive azoospermia
• Infectious diseases in male partner(HIV)
• Severe rhesus isoimmunisation
• Severe defect in semen quality
Donor Insemination

• Indication
• Premature ovarian failure
• Gonadal dysgenesis
• Bilateral oophorectomy
• IVF treatment failure
Oocyte Donation

• Technique that provides genetic and chromosomal information about
the embryo.
• Used to screen for aneuploidy,unbalanced transloations and single
gene defects even before the implantation
PGD

• Normal embryos are implanted and therefore abortion rates are less
• Genetically normal embryos are transferred and therby reducing the
transmission risk
• Reduction in need for genetic testing in pregnancy
Advantages of PGD

Materials that can be used for PGD: polar body biopsy,blastomere
biopsy and trophectoderm biopsy
Polar body biopsy:done by removal of 1 or both of the polar bodies.
Involves testing of only maternal genetic material
Blastomere biopsy: done on day 3 of embryo at the 6-10 cell stage

• Trophoectoderm biospy:
Removed from day 5 embryo.the cellular material is analysed by
1. PCR
2. FISH
3. Comparative genomic hybridization(CGH)

• Couples with known sex linked disease or single gene defects
• Those with an increased risk for aneuploidy:advanced maternal age
,repeated implantation failure with IVF,recurrent pregnancy loss and
translocation carrier status.
Complications: accidental damage to embryo
Indications for PGD

• Literally means cloning
• Process with an exact copy or a duplicate is produced is defined as
cloning
3 types of cloning technologies
• Recombinant deoxyribonucleic acid (DNA) technology or DNA cloning
• Reproductive cloning
• Therapeutic cloning
Cloning

• Women with severe defects or damage to the uterus cannot concieve
• They can have their biological child by undergoing ovarian
stimulation,harvesting the eggs ,fertilizing them with their husband s
sperms and transferring the resulting embryos into another woman s
uterus
Surrogacy

• Uterine anomalies
• Uterine damage
• Medical conditions
Medicolegal and social issues need to be resolved before surrogacy is
considered
Maternal child may complicate the outcome
Indications for surrogacy

• The Indian Council for Medical Research has given Guidelines in the year
2005 regulating Assisted Reproductive Technology procedures. The Law
Commission of India submitted the 228th report on Assisted Reproductive
Technology procedures discussing the importance and need for surrogacy,
and also the steps taken to control surrogacy arrangements. The following
observations had been made by the Law Commission:
• Surrogacy arrangement will continue to be governed by contract amongst
parties, which will contain all the terms requiring consent of surrogate
mother to bear child, agreement of her husband and other family
members for the same, medical procedures of artificial insemination,
reimbursement of all reasonable expenses for carrying child to full term,
willingness to hand over the child born to the commissioning parent(s), etc.
But such an arrangement should not be for commercial purposes.

• A surrogacy arrangement should provide for financial support for
surrogate child in the event of death of the commissioning couple or
individual before delivery of the child, or divorce between the
intended parents and subsequent willingness of none to take delivery
of the child.

• A surrogacy contract should necessarily take care of life insurance
cover for surrogate mother.
• One of the intended parents should be a donor as well, because the
bond of love and affection with a child primarily emanates from
biological relationship. Also, the chances of various kinds of child-
abuse, which have been noticed in cases of adoptions, will be
reduced. In case the intended parent is single, he or she should be a
donor to be able to have a surrogate child. Otherwise, adoption is the
way to have a child which is resorted to if biological (natural) parents
and adoptive parents are different.

• Legislation itself should recognize a surrogate child to be the
legitimate child of the commissioning parent(s) without there being
any need for adoption or even declaration of guardian.
• The birth certificate of the surrogate child should contain the name(s)
of the commissioning parent(s) only.
• Right to privacy of donor as well as surrogate mother should be
protected.
• Sex-selective surrogacy should be prohibited.
• Cases of abortions should be governed by the Medical Termination of
Pregnancy Act 1971 only

• Multiple gestation
• Pregnancy complications
• Congenital anomalies
Complications

male and female infertility

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