Nowdays infertility is major issues world wide,It covers both male and female infertility causes,investigation and related treatments.it also includes recent options available at infertility centres.
3. Introduction
Definition:
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
unexplained.
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4. For management…
Counselling is very important and essential.
Routine examination is not necessary unless indicated by the
history.
History taking is important part in management to find out the
cause.
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.
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5. Classification
Primary infertility: Those patient who have never conceived.
Secondary infertility: It indicates previous pregnancy but
failed to conceive subsequently.
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6. Category 1 Category 2
Young couples married
recently or not having
knowledge regarding fertile
period
Couples married more than 2 year
ago,
Age around 30 years
Particular female with mild male
factor
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Category 3 Category 4
• Any age group but less than
35 years
• Previously diagnosed
condition like tubal block,
endometriosis, severe male
factor
• Old age couples
• Young female with premature
ovarian failure
• Severe uterine problems
9. Initial work up and diagnosis
Initial work up of an infertile couple should be very prompt
and perfect
Investigation should be logical and cost effective
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10. Medical history(female)
History: Age ,duration of marriage, history of previous
marriage
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.
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11. 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
inquired
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12. Medical history:(Male)
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:
Sulphasalazine
Phenothiazine/antipsychotics/metoclopramide
Immunosuppressant/antineoplastic agents
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15. Advice
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
conception
Rubella immunity should be checked, if vaccinated then advise to
avoid pregnancy for at least one month after vaccination
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16. Ovulatory dysfunction
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
ovary
Causes of anovulation
Central
Abnormal feedback
Metabolic
Local ovarian condition
General
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17. Ovulation induction(OI)
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
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18. Clomiphene citrate(CC):
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
development
CC is widely used for ovulation induction in women with
PCOS and in couples with unexplained infertility
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19. 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
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20. 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
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21. 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
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22. Enclomiphene
It appears to have promising future in OI
Synthetic, non steroidal antiestrogen
First line treatment strategy in WHO class 2 anovulatory
infertility
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
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23. Aromatase inhibitors
Currently available drugs are Letrozole, Anastrozole,
Exemestane
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
folliculogenesis
Dose: 1 to 2 mg from day 3 of menstrual cycle daily for 5 days
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24. Letrozole: it is banned due to its associated risk of congenital
cardiac and malformation in newborn.
Indication:
PCOS
CC resistant cases
Situation in which multiple pregnancy is not
desirable or risk of OHSS is high
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25. Moderator/Regulator:
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
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26. Ovulation Induction:
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
PCOS
Agents: FSH, hCG, human menopausal gonadotropin
(hMG)
Success rates
WHO class I: 30% per cycle
WHO class II: 17% per cycle
May include IUI or natural intercourse
hCG
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27. 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
embryos
hCG
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30. OI = ovulation induction COS = controlled ovarian stimulation
IVF = in vitro fertilization IUI = intrauterine insemination
ICSI = Intracytoplasmic sperm injection.
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31. Intrauterine insemination(IUI)
Indications
Unexplained infertility
Male subfertility—mild oligozoospermia, asthenozoospermia, or
teratozoospermia
Failure to conceive after ovulation induction treatment
Ejaculatory failure
Retrograde ejaculation
Procedure
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
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32. In Vitro Fertilization
Procedure
Initially used in women with fallopian tube blockage or
damage
Now employed for many causes of infertility (eg.
Endometriosis, male factor)
Involves
COS
Egg retrieval
Insemination, fertilization, embryo culture
Embryo transfer
Cryopreservation of extra embryos
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33. Risks
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
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34. Intracytoplasmic Sperm Injection
Indications
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
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35. Success Rate and Complications
Fertilization rate: 50%-80%
Live offspring: 20%-40% (40% in younger women, success
declines with maternal age)
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36. References
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.
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