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Management of infertility
 Presented by: Dr. Sheetal M Savaliya
 Guide: Dr. Anil P Singh
 Co-Guide: Dr. Shailesh Mundhava
1
Contents
 Introduction
 Classification
 Initial work up and diagnosis
 Medical history
 Etiology
 Examination
 Investigations
 Treatment
2
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.
3
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.
4
Classification
 Primary infertility: Those patient who have never conceived.
 Secondary infertility: It indicates previous pregnancy but
failed to conceive subsequently.
5
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
6
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
Common causes for male infertility 7
Common causes for female infertility 8
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
9
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.
10
 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
11
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
12
Investigations for male 13
Investigations for female 14
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
15
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
16
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
17
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
18
 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
19
 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
20
 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
21
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
22
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
23
 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
24
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
25
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
26
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
27
Common procedures: COS
IVF
or
ICSI
rFSH/hMG
Day 2 or 3
of menses
GnRH agonist
Cycle day
21-24 Luteal
phase
support
Embryo Transfer
GnRH
antagonist
Day 6 of
FSH
rFSH/hMG
hCG
28
Male infertility treatment
29
OI = ovulation induction COS = controlled ovarian stimulation
IVF = in vitro fertilization IUI = intrauterine insemination
ICSI = Intracytoplasmic sperm injection.
30
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
31
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
32
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
33
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
34
Success Rate and Complications
 Fertilization rate: 50%-80%
 Live offspring: 20%-40% (40% in younger women, success
declines with maternal age)
35
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.
36
THANK YOU
37

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medical management of infertility,think before surgery!!!!

  • 1. Management of infertility  Presented by: Dr. Sheetal M Savaliya  Guide: Dr. Anil P Singh  Co-Guide: Dr. Shailesh Mundhava 1
  • 2. Contents  Introduction  Classification  Initial work up and diagnosis  Medical history  Etiology  Examination  Investigations  Treatment 2
  • 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. 3
  • 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. 4
  • 5. Classification  Primary infertility: Those patient who have never conceived.  Secondary infertility: It indicates previous pregnancy but failed to conceive subsequently. 5
  • 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 6 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
  • 7. Common causes for male infertility 7
  • 8. Common causes for female infertility 8
  • 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 9
  • 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. 10
  • 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 11
  • 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 12
  • 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 15
  • 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 16
  • 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 17
  • 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 18
  • 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 19
  • 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 20
  • 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 21
  • 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 22
  • 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 23
  • 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 24
  • 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 25
  • 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 26
  • 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 27
  • 28. Common procedures: COS IVF or ICSI rFSH/hMG Day 2 or 3 of menses GnRH agonist Cycle day 21-24 Luteal phase support Embryo Transfer GnRH antagonist Day 6 of FSH rFSH/hMG hCG 28
  • 30. OI = ovulation induction COS = controlled ovarian stimulation IVF = in vitro fertilization IUI = intrauterine insemination ICSI = Intracytoplasmic sperm injection. 30
  • 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 31
  • 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 32
  • 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 33
  • 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 34
  • 35. Success Rate and Complications  Fertilization rate: 50%-80%  Live offspring: 20%-40% (40% in younger women, success declines with maternal age) 35
  • 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. 36