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Management of infertility

 Presented by: Dr. Sheetal M Savaliya

 Guide: Dr. Anil P Singh
 Co-Guide: Dr. Shailesh Mundhava

 Introduction
 Classification
 Initial work up and diagnosis
 Medical history
 Etiology
 Examination
 Investigations
 Treatment

Infertility defined as a failure to conceive within one or more
years of regular unprotected intercourse.

 The male is directly responsible in about 30-40 % of

infertility, the female in about 40-55 % and both are
responsible in about 10 percent cases. The remaining 10 % is
For management…

 Counselling is very important and essential.

 Routine examination is not necessary unless indicated by the
 History taking is important part in management to find out the
 The management of the individual couple should always be
discussed in the context of their particular clinical situation.
 Patients should be fully involved in decisions regarding their
treatment and always insist the couple to come together.
Classification 5

 Primary infertility: Those patient who have never conceived.

 Secondary infertility: It indicates previous pregnancy but

failed to conceive subsequently.
Category 1 Category 2
 Young couples married  Couples married more than 2 year
recently or not having ago,
knowledge regarding fertile  Age around 30 years
period  Particular female with mild male

Category 3 Category 4
• Any age group but less than • Old age couples
35 years • Young female with premature
• Previously diagnosed ovarian failure
condition like tubal block, • Severe uterine problems
endometriosis, severe male
Common causes for male infertility 7
Common causes for female infertility 8
Initial work up and diagnosis 9

 Initial work up of an infertile couple should be very prompt

and perfect

 Investigation should be logical and cost effective

Medical history(female) 10

 History: Age ,duration of marriage, history of previous

 General medical history: of STD, tuberculosis, PID, diabetes..
 Surgical history: Abdominal or pelvic history may be related
to peritubal adhesion.
 Menstrual history: Hypomenorrhea, oligomenorrhea to
amenorrhea are associated with disturbed hypothalamopituitary
ovarian axis which may be either primary or secondary to
adrenal or thyroid dysfunction.

 Previous obstetric history: Number of pregnancies, interval

between them and related complication to be inquired. the
history of puerperal sepsis may be responsible for ascending
infection and tubal damage. Uterine synechie may be due to
vigorous curettage.

 Contraceptive practice: IUCD use may cause PID

 Sexual problems: Dyspareunia and loss of libido are to be

Medical history:(Male) 12

 Genital tract infection : Mumps, orchitis, prostatitis

 History of impotence, premature ejaculation, change in libido
 Surgical history of testicular torsion, undescended or maldescended
testis, prostate surgery, hernia repair
 Trauma: genital or inguinal region
 Exposure to lead, cadmium, mercury
 Drug history:
Immunosuppressant/antineoplastic agents
Investigations for male 13
Investigations for female 14
Advice 15
 Regular Sexual intercourse
 Smoking reduces both, women’s fertility as well as semen quality
 Excessive alcohol is detrimental to semen quality and may cause
erectile dysfunction
 A body mass index of more than 29 is associated with reduced
fertility in both men and women
 Folic acid supplement prior to conception and up to 12 weeks of
 Rubella immunity should be checked, if vaccinated then advise to
avoid pregnancy for at least one month after vaccination
Ovulatory dysfunction 16

 Ovulatory dysfunction is a very common problem contributing 25-30

% causes of infertility and 50 % of female infertility
 Normally ovulation requires coordination of central hypothalamic
pituitary axis, the feedback signals and local responses within the
 Causes of anovulation
Abnormal feedback
Local ovarian condition
Ovulation induction(OI) 17

 OI is useful in patients with anovulatory infertility

WHO class I: Hypogonadotrophic hypogonadism
WHO class II: polycystic ovary syndrome (PCOS)
 Goal
Stimulate development of a single follicle that will be able to reach
preovulatory size and rupture

 Options
Clomiphene citrate (CC)
Gonadotropins (hMG/FSH followed hCG)
GnRH analogue
Clomiphene citrate(CC): 18

 CC is an antiestrogen that binds to estrogen receptors and

interferes with estrogen-negative feedback
 Results in an alteration in pulsatile GnRH secretion
 Leads to increases in gonadotropin secretion and follicular

 CC is widely used for ovulation induction in women with

PCOS and in couples with unexplained infertility

 CC treatment successfully induces ovulation in about 80% of

properly selected candidates
 Pregnancy rates are much lower (30%-40% per cycle)
 40%-45% of couples can become pregnant within 6 cycles
 Failure to conceive after successfully induced ovulation is
indication for further evaluation

 Patient characteristics predictive of poor response to CC:

 Hypothalamic disorder
 Low estrogen levels
 Obesity

 CC is generally well tolerated, although some side effects may

limit its efficacy and safety

 Short-term, reversible side effects include: hot flashes, mood

swings, visual disturbances, breast tenderness, pelvic
discomfort, and nausea
 The anti estrogenic effects may negatively impact the uterine
lining, leading to lower pregnancy rates
 Risk of multiple pregnancy is increased
 Risk of cancer is increased among women who were treated
with CC
 Uterine fibroid risk increases with CC treatment
 Risk of ovarian cancer increases among women treated with
prolonged CC
 Dose: 50 mg ,we can increase up to 250 mg but we give upto 150
mg per day due to antiestrogenic effect on endometrium
 Start CC in a dose of 50 mg from day 2,3,4, or 5
 Patient can either ovulate spontaneously or it can be triggered by
hCG when follicle size is 18-22 mm
Enclomiphene 22

 It appears to have promising future in OI

 Synthetic, non steroidal antiestrogen
 First line treatment strategy in WHO class 2 anovulatory
 It has centrally antiestrogenic effect for ovulation induction and
peripherally estrogenic action for endometrial thickening and
increased cervical discharge.
 Dose: 50 mg daily for 5 days from day 2 of menstrual cycle
Aromatase inhibitors

 Currently available drugs are Letrozole, Anastrozole,

 M/A- Centrally it increases gonadotropin secretion and
stimulation of ovarian follicle, peripherally it increases
follicular sensitivity to FSH

 Androgen accumulation in follicle stimulate IGF-1 promoting

 Dose: 1 to 2 mg from day 3 of menstrual cycle daily for 5 days

 Letrozole: it is banned due to its associated risk of congenital

cardiac and malformation in newborn.
 Indication:
CC resistant cases
Situation in which multiple pregnancy is not
desirable or risk of OHSS is high
Moderator/Regulator: 25
Myo-inositol(vitamin B8)

 Phosphatidylinositol 3 kinase production and activation is essential

for insulin to act.
 Myo-inositol has important role in production and activation of PI3
kinase improves insulin’s action and ensure ovulation
 Dose: 2 gm twise a day for 16-20 weeks
 Ovulation rate is around 60-70%
 It reduces testosterone, decreases BMI and decreases hirsuitism.
 Other combination: folic acid and vitamin D
Ovulation Induction: 26
Gonadotropin Treatment
 Optimal for women who have failed CC or who cannot
risk waiting
 Used in women with inadequate pituitary secretion of
LH and FSH (Hypogonadotrophic amenorrhea) or
 Agents: FSH, hCG, human menopausal gonadotropin
 Success rates hCG

 WHO class I: 30% per cycle

 WHO class II: 17% per cycle

 May include IUI or natural intercourse

Controlled ovarian stimulation:
Gonadotropin treatment
 Starts with higher dose of gonadotropins than for OI (COS:
150-225 IU of FSH; OI: 50-75 IU of FSH)
 Needs GnRH analog treatment to prevent interference by
endogenous hormones
 COS is followed by oocyte retrieval, IVF, and transfer of

Common procedures: COS 28

Day 6 of
Day 2 or 3 Embryo Transfer
of menses GnRH
Cycle day
21-24 Luteal
GnRH agonist or phase
Male infertility treatment

OI = ovulation induction COS = controlled ovarian stimulation

IVF = in vitro fertilization IUI = intrauterine insemination
ICSI = Intracytoplasmic sperm injection.
Intrauterine insemination(IUI) 31
Unexplained infertility
Male subfertility—mild oligozoospermia, asthenozoospermia, or
Failure to conceive after ovulation induction treatment
Ejaculatory failure
Retrograde ejaculation
Washed prepared sperm are deposited in the uterus just before the
release of an egg or eggs in a natural or stimulated cycle
Success rate: up to 15% per cycle
Significant risk for multiple pregnancy
In Vitro Fertilization 32

 Initially used in women with fallopian tube blockage or
 Now employed for many causes of infertility (eg.
Endometriosis, male factor)
 Involves
 Egg retrieval
 Insemination, fertilization, embryo culture
 Embryo transfer
 Cryopreservation of extra embryos
 Ovarian hyperstimulation stimulation syndrome
Usually not serious and resolves with outpatient management
1%-2% severe requiring hospitalization
Dose-dependent, avoided by careful titration
 Anesthesia
 Multiple births
 Ectopic pregnancy
 Cost
 Psychologic distress
Intracytoplasmic Sperm Injection 34


 Very low numbers of motile sperm

 Severe teratospermia
 Problems with sperm binding to and penetrating the egg
 Antisperm antibodies
 Prior or repeated fertilization failure with standard IVF methods
 Obstruction of the male reproductive tract not amenable to repair

Success Rate and Complications

 Fertilization rate: 50%-80%

 Live offspring: 20%-40% (40% in younger women, success

declines with maternal age)
References 36

1. Sushma D, editor. Infertility management made easy. 2nd ed. New

Delhi: Jaypee brothers medical publishers (p) LTD; 2014.

2. Keith LP, Bernard PS. Introduction To Endocrinology: The

Hypothalamic-Pituitary axis. Brunton LL, Goodman & Gilman’s
the pharmacological basis of therapeutics.11th Ed. Mcgraw-hill:
Medical Publishing Division;2006. P. 1117-24.

3. Dutta DC, Textbook of gynecology, 6th ed. New Delhi: Jaypee

brothers medical publishers (p) LTD; 2013.