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Evaluation of a couple
with infertility
Dr Arthur M
OUTLINE
• Objectives
• Definition
• Epidemiology
• Timing of Evaluation
• Evaluating female infertility and management
• Evaluating male infertility and management
• Summary
• References
OBJECTIVES
The students should be able to cite:
• Definition of primary and secondary infertility
• Causes of male and female infertility
• Evaluation and management
DEFINITION
An inability of a couple to conceive after:
• 12 mon of regular intercourse without use of contraception
in women <35yrs
• 6 mon of regular intercourse without use of contraception in
women >35yrs
PRIMARY INFERTILITY: applies to couples who have never
conceived.
SECONDARY INFERTILITY: implies that the couple have had
atleast a prior pregnancy irrespective of the outcome
PREVALENCE
• According to a WHO meta-analysis of 277 surveys from 27 countries
comparing data from 1990 and 2010, among women 20-44yrs who
were exposed to the risk of pregnancy 1.9% were unable to attain a
live birth (primary).
• Out of women who had had at least one live birth and were exposed
to the risk of pregnancy 10.5% were unable to have another child
(Secondary).
• Infertility prevalence was highest in South Asia, Sub-Saharan Africa,
North Africa/middle east & central Asia.
• However, the level of infertility in 2010 were similar to those in 1990
• Due to population growth, the absolute number of couples has
increased from 42.0 mil (1990) to 48.5mil (2010)
Figure 1. Global prevalence of primary and secondary infertility in 2010, by the female partner's
age.
Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA (2012) National, Regional, and Global Trends in Infertility Prevalence Since
1990: A Systematic Analysis of 277 Health Surveys. PLOS Medicine 9(12): e1001356. https://doi.org/10.1371/journal.pmed.1001356
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001356
PREVALENCE CONT’D
According to a WHO study involving 8500 infertile couples:
• Female factor was reported in 37% of couples
• Male factor infertility in 8%
• Both male & female factors in 35%
• 5% were idiopathic
• 15% became pregnant during the study
TIMING OF EVALUATION
• Undertaken for couples who are not able to conceive after
12mon of unprotected and frequent intercourse
• Earlier in those with a significant medical history and physical
findings
• In women over 35yrs of age
THE FEMALE PARTNER
CAUSES OF INFERTILITY (females)
Ovulatory factor
• Central defects: Hyperprolactinemia, Hypothalamic
insufficiency, Pituitary insufficiency
• Peripheral defects: Gonadal dysgenesis, Premature ovarian
failure, Ovarian tumour, Ovarian resistance
• Metabolic diseases: Thyroid, liver or renal disease, Obesity,
Androgen excess
Pelvic factor
• Infections: Appendicitis, Pelvic Inflammatory Disease,
Uterine adhesions.
• Endometriosis
• Structural abnormalities: Diethylstilbestrol (DES) exposure,
Failure of fusion of the reproductive tract
• Myoma
Cervical Factor
• Congenital: DES exposure, Mullerian duct abnormality
• Acquired: surgical treatment, infection
History and Physical Examination
History:
• Duration of infertility and results of previous evaluation and
therapy
• Menstrual hx: cycle length and characteristics
• Medical, surgical & gynae hx: STIs, PID, thyroid disease,
galactorrhoea, hirsutism, dysmenorrhea, unilateral
oophorectomy etc
• Obstetric hx: hx of past pregnancies if any
• Sexual hx: sexual dysfunction, frequency of coitus
• Fam hx: infertility, birth defects, genetic mutations
• Social hx: smoking, alcohol use, changes in weight
Physical Examination
General appearance:
• Assess BMI, Body habitus (short & stocky w/ squarely shaped
chest). Secondary sexual characteristics (breast enlargement,
develpment of pubic and axillary hair etc)
• Signs of androgen excess: hirsutism, acne, baldness
• Signs of thyroid disease: enlarge thyroid
Abdominal & pelvic exam:
• Uterine enlargement (leiomyomas), adnexal tenderness or
masses (chronic PID, endometriosis)
Diagnostic tests
Assessment of ovulatory function
• Mid luteal phase serum progesterone level: if >3ng/ml is evidence of
ovulation. But if <3ng/ml; evaluate for causes of anovulation w/
serum prolactin, TSH & FSH
• Urinary LH surge: if positive indicates ovulation
Assessment of ovarian reserve
• Day 3 FSH: if <10 mIU/ml indicates adequate reserve; between 10-15
mIU/ml is borderline; if >20 mIU/ml indicates poor reserve.
• Day 3 Estradiol: if <80ng/ml adequate ovarian reserve but if >80ng/ml
suggest advanced premature follicle recruitment.
CONT’D
• CCCT: if Day 10 FSH <10mIU/ml indicates adequate ovarian
reserve; 10-15mIU/ml borderline; and if >20mIU/ml, poor
reserve
• Anti Mullerian Hormone (AMH): 0.5-1.0ng/ml predicts
ovarian reserve. Undetectable at menopause.
Assessment of fallopian tube patency
• Hysterosalpingogram (HSG): congenital malformations of
uterus, submucousal leiomyomas, intrauterine synechiae,
proximal or tubal occlusion.
• Hysterosalpingo-contrast-sonography (HyCoSy)
CONT’D
Assessment of the uterine cavity
• Saline infusion sonohysterography: intrauterine adhesions,
polyps and congenital anomalies.
• Hysteroscopy
Role of Laparoscopy
• Only indicate for women whom endometriosis or adhesions/
tubal disease is suspected based on Hx and PE
• Advantages: surgical therapy can be initiated.
Other tests of limited clinical utility
• Endometrial biopsy: done only when endometrial pathology
strongly suspected.
• Basal Body temperature
Treatment
Ovulatory factor
• Clomiphene Citrate: 50-100mg/d, given for 5 days from day 3-5 of the
cycle
• Letrozole: 2.5-7.5mg/d
• Gonadotropins IM or recombinant FSH sub-cut
• In-vitro-fertilization (IVF)
Pelvic factor
• Surgery
Cervical factor
• Antibiotics for infections
• Surgery
• Intrauterine insemination
THE MALE PARTNER
CAUSES OF MALE INFERTILITY
• Endocrine disorders: hypothalamic dysfunction, pituitary failure,
hyperprolactinemia, exogenous androgens, thyroid disorders
• Anatomic disorders: congenital absence of vas deferens,
obstruction of vas deferens
• Abnormal spermatogenesis: chromosomal abnormalities,
mumps orchitis, cryptorchidism, chemical/radiation exposure
• Abnormal motility: absent cilia (kartagener’s syndrome),
varicocele
• Sexual dysfunction: retrograde ejaculation, impotence,
decreased libido
History and Physical Examination
History
• Sexual development hx: testicular descent, pubertal
development, loss of body hair or decrease in shaving frequency
• Chronic severe systemic illness and hx of major head/pelvic
trauma
• Infections: mumps orchitis, STIs, prostatitis
• Surgical: vasectomy or orchiectomy
• Drug and environmental exposures: alcohol, tobacco,
corticosteroids, cytotoxic chemo, toxic chemicals e.g. pesticides
• Sexual hx: libido, frequency of intercourse, previous fertility
assessment
Physical Examination
Skin:
• loss of pubic, axillary and facial hair, decreased oiliness of the
skin and fine facial wrinkling
• Thin skin, ecchymoses and/or broad purple striae
External genitalia:
• Small testes if <3.6cm
• Check scrotum for large varicoceles
DIAGNOSTIC TESTS
Semen Analysis: collected after 2-7d of abstinence
Normal semen parameters:
• Volume- 1.5mL
• Sperm conc: 15mil sperm/mL
• Total sperm number: 39mil sperms per ejaculate
• Morphology- 4% normal forms
• Vitality- 58% live
• Progressive motility- 32%
• Total (progressive + non-progressive) motility: 40%
Semen Analysis interpretation
Low volume:
• Low volume w/ normal conc: due to incomplete ejaculate or
partial retrograde
• Low volume w/ low conc: testosterone deficiency
• Low volume w/ azoospermia or severe oligozoospermia:
genital tract obstruction
Low concentration:
• Rule out retrograde ejaculation or congenital absence of the
vas deferens
CONT’D
Abnormal morphology:
• Head, neck and tail defects: chromosomal abnormalities
• Presence of leukocytes
• Small size
FURTHER INVESTIGATIONS
Endocrine testing: Serum total testosterone, LH and FSH
• testosterone w/ FSH & LH: primary hypogonadism
• Normal testosterone & LH w/ FSH: primary hypogonadism
• testosterone w/ FSH & LH: Secondary hypogonadism
• Normal testosterone, FSH & LH: further evaluation depends
on semen analysis
• sperm count & very LH in muscular man: androgen abuse
CONT’D
• Scrotal & transrectal USS
Transrectal USS Scrotal doppler USS (varicoceles)
Genetic tests
Karyotyping:
• Y chromosome microdeletions
• Klinefelter syndrome (XXY)
• CFTR gene
TREATMENT
Mild to Moderate disease
• Intrauterine insemination
Severe disease
• Intracytoplasmic sperm injection (ICSI) + In-vitro-fertilization (IVF)
• Indications: poor semen analysis, fertilization failure with standard IVF
Other tx
• Surgical reanastomosis
• FSH replacement or GnRH
• Donor sperm
SUMMARY
• Infertility is classically defined as the failure of a couple to
conceive after 12 months of frequent intercourse without
use of contraception in women under age 35, and after six
months in women over age 35.
• 85 to 90% of couples will conceive within 12 months of
attempting pregnancy.
• Infertility can be due to male factors, female factors, or
factors contributed by both partners.
• Components of the basic infertility evaluation include history
and physical examination and diagnostic tests
• Once the cause of infertility is identified, therapy aimed at
correcting reversible aetiologies
REFERENCES
• Current diagnosis & treatment (Obstetrics & Gynaecology),. 11th
edition,. Decherney A et al. Pg 879-888
• Uptodate @ https://www.uptodate.com/contents/overview-of-
infertility?search=evaluation%20of%20infertility&source=search_resul
t&selectedTitle=2~150&usage_type=default&display_rank=2
Questions……..comments….…suggestions
THANK YOU!!!

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Evaluating a couple with infertility

  • 1. Evaluation of a couple with infertility Dr Arthur M
  • 2. OUTLINE • Objectives • Definition • Epidemiology • Timing of Evaluation • Evaluating female infertility and management • Evaluating male infertility and management • Summary • References
  • 3. OBJECTIVES The students should be able to cite: • Definition of primary and secondary infertility • Causes of male and female infertility • Evaluation and management
  • 4. DEFINITION An inability of a couple to conceive after: • 12 mon of regular intercourse without use of contraception in women <35yrs • 6 mon of regular intercourse without use of contraception in women >35yrs PRIMARY INFERTILITY: applies to couples who have never conceived. SECONDARY INFERTILITY: implies that the couple have had atleast a prior pregnancy irrespective of the outcome
  • 5. PREVALENCE • According to a WHO meta-analysis of 277 surveys from 27 countries comparing data from 1990 and 2010, among women 20-44yrs who were exposed to the risk of pregnancy 1.9% were unable to attain a live birth (primary). • Out of women who had had at least one live birth and were exposed to the risk of pregnancy 10.5% were unable to have another child (Secondary). • Infertility prevalence was highest in South Asia, Sub-Saharan Africa, North Africa/middle east & central Asia. • However, the level of infertility in 2010 were similar to those in 1990 • Due to population growth, the absolute number of couples has increased from 42.0 mil (1990) to 48.5mil (2010)
  • 6. Figure 1. Global prevalence of primary and secondary infertility in 2010, by the female partner's age. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA (2012) National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys. PLOS Medicine 9(12): e1001356. https://doi.org/10.1371/journal.pmed.1001356 https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001356
  • 7. PREVALENCE CONT’D According to a WHO study involving 8500 infertile couples: • Female factor was reported in 37% of couples • Male factor infertility in 8% • Both male & female factors in 35% • 5% were idiopathic • 15% became pregnant during the study
  • 8. TIMING OF EVALUATION • Undertaken for couples who are not able to conceive after 12mon of unprotected and frequent intercourse • Earlier in those with a significant medical history and physical findings • In women over 35yrs of age
  • 10. CAUSES OF INFERTILITY (females) Ovulatory factor • Central defects: Hyperprolactinemia, Hypothalamic insufficiency, Pituitary insufficiency • Peripheral defects: Gonadal dysgenesis, Premature ovarian failure, Ovarian tumour, Ovarian resistance • Metabolic diseases: Thyroid, liver or renal disease, Obesity, Androgen excess
  • 11. Pelvic factor • Infections: Appendicitis, Pelvic Inflammatory Disease, Uterine adhesions. • Endometriosis • Structural abnormalities: Diethylstilbestrol (DES) exposure, Failure of fusion of the reproductive tract • Myoma Cervical Factor • Congenital: DES exposure, Mullerian duct abnormality • Acquired: surgical treatment, infection
  • 12. History and Physical Examination History: • Duration of infertility and results of previous evaluation and therapy • Menstrual hx: cycle length and characteristics • Medical, surgical & gynae hx: STIs, PID, thyroid disease, galactorrhoea, hirsutism, dysmenorrhea, unilateral oophorectomy etc • Obstetric hx: hx of past pregnancies if any • Sexual hx: sexual dysfunction, frequency of coitus • Fam hx: infertility, birth defects, genetic mutations • Social hx: smoking, alcohol use, changes in weight
  • 13. Physical Examination General appearance: • Assess BMI, Body habitus (short & stocky w/ squarely shaped chest). Secondary sexual characteristics (breast enlargement, develpment of pubic and axillary hair etc) • Signs of androgen excess: hirsutism, acne, baldness • Signs of thyroid disease: enlarge thyroid Abdominal & pelvic exam: • Uterine enlargement (leiomyomas), adnexal tenderness or masses (chronic PID, endometriosis)
  • 14.
  • 15. Diagnostic tests Assessment of ovulatory function • Mid luteal phase serum progesterone level: if >3ng/ml is evidence of ovulation. But if <3ng/ml; evaluate for causes of anovulation w/ serum prolactin, TSH & FSH • Urinary LH surge: if positive indicates ovulation Assessment of ovarian reserve • Day 3 FSH: if <10 mIU/ml indicates adequate reserve; between 10-15 mIU/ml is borderline; if >20 mIU/ml indicates poor reserve. • Day 3 Estradiol: if <80ng/ml adequate ovarian reserve but if >80ng/ml suggest advanced premature follicle recruitment.
  • 16. CONT’D • CCCT: if Day 10 FSH <10mIU/ml indicates adequate ovarian reserve; 10-15mIU/ml borderline; and if >20mIU/ml, poor reserve • Anti Mullerian Hormone (AMH): 0.5-1.0ng/ml predicts ovarian reserve. Undetectable at menopause. Assessment of fallopian tube patency • Hysterosalpingogram (HSG): congenital malformations of uterus, submucousal leiomyomas, intrauterine synechiae, proximal or tubal occlusion. • Hysterosalpingo-contrast-sonography (HyCoSy)
  • 17.
  • 18. CONT’D Assessment of the uterine cavity • Saline infusion sonohysterography: intrauterine adhesions, polyps and congenital anomalies. • Hysteroscopy Role of Laparoscopy • Only indicate for women whom endometriosis or adhesions/ tubal disease is suspected based on Hx and PE • Advantages: surgical therapy can be initiated.
  • 19.
  • 20. Other tests of limited clinical utility • Endometrial biopsy: done only when endometrial pathology strongly suspected. • Basal Body temperature
  • 21. Treatment Ovulatory factor • Clomiphene Citrate: 50-100mg/d, given for 5 days from day 3-5 of the cycle • Letrozole: 2.5-7.5mg/d • Gonadotropins IM or recombinant FSH sub-cut • In-vitro-fertilization (IVF) Pelvic factor • Surgery Cervical factor • Antibiotics for infections • Surgery • Intrauterine insemination
  • 23. CAUSES OF MALE INFERTILITY • Endocrine disorders: hypothalamic dysfunction, pituitary failure, hyperprolactinemia, exogenous androgens, thyroid disorders • Anatomic disorders: congenital absence of vas deferens, obstruction of vas deferens • Abnormal spermatogenesis: chromosomal abnormalities, mumps orchitis, cryptorchidism, chemical/radiation exposure • Abnormal motility: absent cilia (kartagener’s syndrome), varicocele • Sexual dysfunction: retrograde ejaculation, impotence, decreased libido
  • 24. History and Physical Examination History • Sexual development hx: testicular descent, pubertal development, loss of body hair or decrease in shaving frequency • Chronic severe systemic illness and hx of major head/pelvic trauma • Infections: mumps orchitis, STIs, prostatitis • Surgical: vasectomy or orchiectomy • Drug and environmental exposures: alcohol, tobacco, corticosteroids, cytotoxic chemo, toxic chemicals e.g. pesticides • Sexual hx: libido, frequency of intercourse, previous fertility assessment
  • 25. Physical Examination Skin: • loss of pubic, axillary and facial hair, decreased oiliness of the skin and fine facial wrinkling • Thin skin, ecchymoses and/or broad purple striae External genitalia: • Small testes if <3.6cm • Check scrotum for large varicoceles
  • 26.
  • 27. DIAGNOSTIC TESTS Semen Analysis: collected after 2-7d of abstinence Normal semen parameters: • Volume- 1.5mL • Sperm conc: 15mil sperm/mL • Total sperm number: 39mil sperms per ejaculate • Morphology- 4% normal forms • Vitality- 58% live • Progressive motility- 32% • Total (progressive + non-progressive) motility: 40%
  • 28. Semen Analysis interpretation Low volume: • Low volume w/ normal conc: due to incomplete ejaculate or partial retrograde • Low volume w/ low conc: testosterone deficiency • Low volume w/ azoospermia or severe oligozoospermia: genital tract obstruction Low concentration: • Rule out retrograde ejaculation or congenital absence of the vas deferens
  • 29. CONT’D Abnormal morphology: • Head, neck and tail defects: chromosomal abnormalities • Presence of leukocytes • Small size
  • 30. FURTHER INVESTIGATIONS Endocrine testing: Serum total testosterone, LH and FSH • testosterone w/ FSH & LH: primary hypogonadism • Normal testosterone & LH w/ FSH: primary hypogonadism • testosterone w/ FSH & LH: Secondary hypogonadism • Normal testosterone, FSH & LH: further evaluation depends on semen analysis • sperm count & very LH in muscular man: androgen abuse
  • 31. CONT’D • Scrotal & transrectal USS Transrectal USS Scrotal doppler USS (varicoceles)
  • 32. Genetic tests Karyotyping: • Y chromosome microdeletions • Klinefelter syndrome (XXY) • CFTR gene
  • 33. TREATMENT Mild to Moderate disease • Intrauterine insemination Severe disease • Intracytoplasmic sperm injection (ICSI) + In-vitro-fertilization (IVF) • Indications: poor semen analysis, fertilization failure with standard IVF Other tx • Surgical reanastomosis • FSH replacement or GnRH • Donor sperm
  • 34. SUMMARY • Infertility is classically defined as the failure of a couple to conceive after 12 months of frequent intercourse without use of contraception in women under age 35, and after six months in women over age 35. • 85 to 90% of couples will conceive within 12 months of attempting pregnancy. • Infertility can be due to male factors, female factors, or factors contributed by both partners. • Components of the basic infertility evaluation include history and physical examination and diagnostic tests • Once the cause of infertility is identified, therapy aimed at correcting reversible aetiologies
  • 35. REFERENCES • Current diagnosis & treatment (Obstetrics & Gynaecology),. 11th edition,. Decherney A et al. Pg 879-888 • Uptodate @ https://www.uptodate.com/contents/overview-of- infertility?search=evaluation%20of%20infertility&source=search_resul t&selectedTitle=2~150&usage_type=default&display_rank=2