Helpful for medical students

1. Evaluation and treatment of Infertility
Zelele ,MD
Obstetrician and Gynecologist
April 2021

2. Introduction
Infertility is defined as the inability to conceive after 1 year
of unprotected intercourse of reasonable frequency
It affects 10 to 15% of reproductive-aged couples

3. Introduction…
A monthly probability of conceiving is 20 to 25%
In those attempting conception, more than 85 percent will be pregnant
by 1 year and the fecundability of normal couples over 2 years is 93 %
In general, infertility evaluation is offered to any couple that has failed
to conceive in 1 year

4. Etiology of infertility
Successful pregnancy requires a complex sequence of events
 Ovulation
 Ovum pick-up by a fallopian tube
 Sperm of adequate number and quality
 Fertilization
 Transport of a fertilized ovum into the uterus
 Implantation into a receptive uterine cavity
Both partners are urged to attend the initial consultation

5. Etiology of infertility…
Ovulatory……………….27%
Tubal/uterine……………22%
Male…………………….25%
Other…………………….9%
Unexplained…………….17%

6. Etiology of infertility…
The infertility evaluation can be conceptually simplified:
 Confirmation of ovulation status
 Evaluation of female reproductive tract anatomy, &
 Evaluation of male partner

7. Evaluation for anovulation
Ovulation may be perturbed by abnormalities within the
hypothalamus, anterior pituitary, or ovaries
 Hypothalamic disorders
1. Acquired
 Excessive exercise
 Eating disorders
 Stress
2. Inherited
 IHH or kallamann syndrome
Thyroid disease and hyperprolactinemia also may contribute to
menstrual disturbances
 Measurement of TSH is considered reasonable in any infertile woman

8. Clinical evaluation for ovulation
A patient's menstrual history is an excellent predictor of regular ovulation
 A woman with cyclic menses at an interval of 24 to 38 days and duration of
bleeding of 3 to 7 days is most likely ovulating
Probable ovulation is also suggested by midcycle pelvic pain ,breast
tenderness, acne, food cravings, and mood changes
Basal body temperature (BBT)
 Morning oral temperatures are usually 97.0° to 98.0°F during the follicular phase
 A postovulatory rise in progesterone levels increases basal temperature by
approximately 0.4° to 0.8°F

9. Evaluation for ovulation…
Ovulation predictor kits
 These kits measure urinary LH concentration by colorimetric assay
 In general, a woman begins testing 2 to 3 days prior to the predicted LH surge,
and testing is continued daily
 In most instances, ovulation will occur the day following the urinary LH peak
 If equivocal results are obtained, the test can be repeated in 12 hours

10. Evaluation for ovulation…
Serum Progesterone
 Day 21 progesterone
Values above 4 to 6 ng/mL correlate with ovulation and progesterone production by the
corpus luteum
Adequate progesterone levels are required for endometrial preparation prior to
implantation
Endometrial Biopsy
 It is no longer considered a routine part of infertility evaluation
High intraobserver and interobserver variability during histologic evaluation
Sonography
 Serial ovarian sonographic evaluations can demonstrate the development of a
mature antral follicle and its subsequent collapse during ovulation

11. Evaluation for diminished ovarian reserve
Ovulatory status does not provide a complete picture of ovarian
function
An array of tests has been developed to assess ovarian reserve
 Follicle-Stimulating Hormone (FSH) and Estradiol
 Antimullerian hormone (AMH)
 Antral Follicle Count (AFC)
 Abnormal test findings correlate with a poorer prognosis for
achieving pregnancy, and referral to an infertility specialist is
advisable

12. Age and reproduction in women
Female age and fertility have a
clear inverse relationship
 After ages 34, 40, and 45, the
incidence of infertility was 11
percent, 33 percent, and 87
percent, respectively
 This loss is primarily attributable
to a decline in oocyte quality and
quantity

13. Follicle-stimulating hormone and Estradiol
A Cycle day 3 FSH
 With loss of luteal inhibin, FSH levels rise in the early follicular phase
 A value > 10 mlU/mL may indicate significant loss of ovarian reserve
and prompt more complete evaluation
A cycle-day-3 estradiol level >80 pg/mL is considered abnormal

14. Antimullerian hormone
AMH is expressed by the granulosa cells of small preantral follicles
but has limited expression in larger follicles
This suggests that AMH plays a role in dominant follicle recruitment
Benefit of AMH over FSH
 AMH expression is consistent across cycle stages
 AMH levels correlate more strongly with ovarian primordial follicle number
 Drop in AMH level is an earlier marker of waning ovarian function

15. Antral follicle count
AFC is commonly used as a reliable predictor for subsequent
response to ovulation induction
Antral follicles between 2 and 10 mm are counted in both ovaries
An AFC with <3-6 total antral follicles predicts poor response
to gonadotropin stimulation during IVF cycles

16. Evaluation for female anatomic abnormalities
1. Hysterosalpingography
It can display the shape and size of the uterine cavity and define tubal status
Many causes of tubal disease affect both tubes, and thus unilateral disease is unusual.
 Unilateral obstruction with a normal contralateral tube most likely reflects dye following the
path of least resistance during the HSG procedure
2. Sonography
TVS determine uterine anatomy
SIS detects endometrial defects
SIS is generally less painful than HSG and does not require radiation exposure
3. Laparoscopy
It is gold standard approach for pelvic pathology
 Direct inspection provides the most accurate assessment of pelvic pathology
It allows both diagnosis and immediate surgical treatment of abnormalities such as
endometriosis or pelvic adhesions
Methylene blue is commonly used for Chromotubation
4. Hysteroscopy
It is the preferred method to determine intrauterine abnormalities

17. Evaluation for female anatomic abnormalities…
Tubal and pelvic factors
 PID
 Genital tuberculosis→3-5 % of infertility cases
o The likelihood of a return to fertility after antitubercular treatment is low, and IVF with
embryo transfer remains the most reliable approach
 Endometriosis
o With endometriosis, chronic inflammation and intraperitoneal bleeding can lead to pelvic
adhesions
 It also diminish fertility by an increase in peritoneal fluid inflammatory factors, alterations
in endometrial immunologic function, poor oocyte or embryonic quality, or impaired
implantation
 Prior pelvic surgery

18. Uterine Abnormalities
Congenital
The fertility effects of these
anomalies have been difficult to
verify
 Uterine septum
 Bicornuate uterus
 Unicornuate uterus
 Uterine didelphys
Acquired
Leiomyomas
Adenomyosis
Endometrial polyps
Asherman syndrome
 Prior uterine dilation and curettage ,
and genital tuberculosis is risk factor
 The clinical history will often include
an acute postsurgical decline in
menstrual bleeding or even
amenorrhea

19. Leiomyomas
Most experts suggest removal of submucosal fibroids that
significantly distort the endometrial cavity
Leiomyomas may diminish fertility by proposed mechanisms that
include:
 Endometrial cavity distortion with associated changes in blood flow and
endometrial maturation
 Endometrial inflammation
 Disordered uterine contractility that may hinder sperm or embryo
transport
 Obstruction of the proximal fallopian tubes; or
 Interference with ovum capture

20. Cervical factors
The cervical glands secrete mucus that is normally thick and
impermeable to sperm and ascending infections
 High estrogen levels at midcycle induce mucus to become thin and stretchy
and to have a higher sodium chloride concentration
o Estrogen primed cervical mucus filters out nonsperm components of semen and forms
channels that help direct sperm into the uterus
o Midcycle mucus also creates a reservoir for sperm.
 This allows ongoing release during the next 24 to 72 hours and extends the potential time for
fertilization

22. Evaluation of male infertility
Causes of male infertility can roughly be categorized as:
 Abnormalities of sperm production, sperm function, or obstruction of the
ductal outflow tract
o In a fertile male, approximately 100 to 200 million sperm are produced each day
 Normal sexual function with appropriate deposition of sperm during
intercourse is also required
Male fertility likely diminishes modestly with aging
 Pregnancy rates decline and time to conception lengthens
 Outside of semen parameters, the higher incidence of erectile and other
sexual dysfunction with male aging undoubtedly contributes to
lower conception rates

23. Semen analysis
Collection
 The male refrains from ejaculation for 2 to 3 days, and a specimen is collected
by masturbation into a sterile cup
 Importantly, the sample should arrive in the laboratory within an hour of
ejaculation to allow for optimal analysis
 Ideally, two semen samples separated by at least a month are analyzed
 In practice, frequently only a single sample is analyzed if parameters are
normal

24. Semen analysis results
Nearly 80% of semen volume
comes from the seminal vesicles
Seminal fluid is alkaline and is
thought to protect sperm from
acidity in prostatic secretions and
in the vagina
Seminal fluid also provides
fructose as an energy source for
sperm
An acidic pH or lack of fructose is
consistent with obstruction of the
efferent ductal system

25. Semen analysis..
Partial or complete vas deferens
obstruction may be caused by
infection, tumor, prior testicular or
inguinal surgery, or trauma
Retrograde ejaculation follows
failed closure of the bladder neck
during ejaculation and allows
seminal fluid to
flow backward into the bladder
 Retrograde ejaculation is suspected in
men with diabetes mellitus, spinal
cord damage, or prior prostate or
other retroperitoneal surgery that may
have damaged nerves

26. Semen analysis
Azoospermia may result from
outflow tract obstruction, termed
obstructive azoospermia, such as
that which occurs with
congenital absence of the vas
deferens, severe infection, or
vasectomy
Azoospermia may also follow
testicular failure (nonobstructive
azoospermia)
To differentiate between dead
and nonmotile sperm,a
hypoosmotic swelling test can be
completed.
 When mixed with a hypoosmotic
solution, living, nonmotile sperm
with normal membrane function
swell and coil as fluid is absorbed

27. Hormonal evaluation
Essentially, abnormalities may be due
to central defects in hypothalamic-
pituitary function or to defects within
the testes
Most urologists will defer testing
unless a sperm concentration is below
10 million/ml
Testing will include measurements of
serum FSH and testosterone levels,
and TSH and prolactin levels are
considered
Low FSH and low testosterone levels
are consistent with hypothalamic
dysfunction, such as IHH or Kallmann
syndrome
In these patients, sperm production
may be achieved with gonadotropin
treatment
Elevated FSH and low testosterone
levels provide evidence of testicular
dysfunction, and most men with
oligospermia are in this category
 testosterone replacement will not rescue
sperm production
 In fact, replacement will decrease
gonadotropin stimulation of remaining
testicular function through negative
feedback at the hypothalamus and
pituitary

28. Other evaluations
Imaging
 Scrotal sonography is a common approach used to examine testicular
morphology and identify varicocele or epididymal cysts or abscesses
Testicular biopsy
 To determine whether viable sperm are present in the seminiferous tubules
Genetic Screening
 karyotype testing should be performed for any male with severe oligospermia
(<5 x 106 sperm/mL) or nonobstructive azoospermia (WHO)

29. Treatment of infertility
It is a complex process influenced by numerous factors
Important considerations include duration of infertility, a couple's age
(especially the female's), and diagnosed cause
In general, initial steps strive to identify a primary cause and
contributing factors and the treatment is aimed at their direct
correction and is typically medication or surgery

31. Management principles
Life style therapies
 Weight optimization
o It should be recommended as first-line management of obese women with PCOS
 Exercise
o Physical activity has numerous health benefits
 Nutrition
o Daily multivitamin supplementation for both is reasonable
o Folic acid is contained in most multivitamins, and daily doses of 400 µg orally are
recommended for women attempting pregnancy to reduce the
incidence of neural-tube defects in their fetuses
 Stress management
Ovulation Induction
Correction of DOR
Correction of anatomic abnormalities

32. Correction of diminished ovarian reserve
A basal (day 2 or 3) FSH level above 15 IU/L predicts that medical
therapies will be of little benefit
Patients with a low AMH level (<1ng/mL) generally respond poorly
to gonadotropins
Options
 Donor eggs
 Adoption
 Expectant mgt

33. Abnormal semen volume
Anejaculation or anorgasmia
 psychologic counseling
 Sildenafil for erectile dysfunction
 Vibratory stimulation
 Electroejaculation for spinal cord injuries unresponsive to other therapy
Retrograde Ejaculation
 Alpha adrenergic agents
 Pseudoephedrine po
 IUI-sperm retrieved from urine
 Oral sodium bicarbonate protect sperm from low PH of urine
Failure of emission
 Sympathomimetic agents
 Testicular or epidydymal extraction of sperm for cases refractory to medications and use the
retrieved sperm for ICSI

34. Abnormal Sperm Count
Obstructive azoospermia
 Prior vasectomy or ejaculatory
duct obstruction
amenable to surgical treatment
 congenital bilateral absence of the
vas deferens (CBAVD)
TESE with ICSI
Nonobstructive azoospermia
 Klinefelter syndrome (47,XXY) or
balanced translocation; deletion of
a small portion of the Y
chromosome; testicular failure; or
unexplained causes
 TESE with ICSI for 47,xxy and y
microdeletion of the AZFc region

35. Oligozoospermia
• Causes are varied and include hormonal, genetic, environmental
(including medications), and unexplained causes.
• Additionally, an obstructive cause, especially ejaculatory duct
obstruction, should be considered if oligozoospermia accompanies low
semen volume
• Oligozoospermia without decreased sperm motility commonly reflects
hypogonadotropic hypogonadism
• In general, hypogonadotropic hypogonadism is best treated with
FSH and hCG administered to the male

36. Abnormal sperm motility or morphology
In general, asthenospermia does not respond to directed treatments
For treatment, IUI and ICSI are preferred
If fewer than 1 million motile sperm are available for insemination
following semen processing or the couple has experienced more than 5
years of infertility, ICSI is considered as initial therapy
Directed treaments for teratozoospermia are not available
ICSI is considered if ART is selected

37. Unexplained infertility
Its reported prevalence reaches up to 30 percent
The diagnosis is highly subjective and depends
on the diagnostic tests performed or omitted and on their quality
Expectant management may be considered especially with
infertility of short duration and with relatively young maternal
age
However, if treatment is desired, IUI, superovulation, and
ART are empiric appropriate interventions to consider

38. Infertility testing summary
Ovulatory function/ovarian reserve
 Ovulation predictor kit
 Early follicular FSH +/- Estradiol level
 Antimullerian hormone(AMH)
 Antral follicle count
Tubal/pelvic disease
 Hysterosalpingography
 Laparoscopy +Chromotubation
Uterine factors
 Hysterosalpingography
 Transvaginal sonography/saline-infusion sonography
+/-MRI
 Hysteroscopy+/-laparoscopy
Male factor
 Semen analysis