Estrogens - An excess of sex steroids, either estrogens or androgens, can cause male infertility due to an imbalance in the testosterone-estrogen ratio. E.g Hepatic cirrhosis, adrenocortical tumour. 2.Androgens - An excess of androgens can suppress pituitary gonadotropin secretion and lead to secondary testis failure. The use of exogenous androgenic steroids (anabolic steroids) result in temporary sterility due to this effect. 3. Glucocorticoids - Exposure to excess glucocorticoids either endogenously or exogenously can result in decreased spermatogenesis. Elevated plasma cortisone levels depress LH secretion and induce secondary testis failure. 4. Hyper- and hypothyroidism - Abnormally high or low levels of serum thyroid hormone affect spermatogenesis Thyroid abnormalities are a rare cause (0.5%) of male infertility. 5. Growth hormone - Some infertile men have deficient responses to growth hormone challenge tests and may respond to growth hormone treatment with improvements in semen quality
A 33 years old Omani lady k/o primary infertility was present to the A&E with referral
from private clinic .
She presented with sever lower abdominal pain from 3 days which get worse
with time. It was colicky in nature, not radiating, and she can’t tolerated
with it. There was history of abdominal distention, SOB, vomiting and
4 days before pt. underwent Intra cytoplasmic sperm injection (ICSI)
12-19/1/2013 : fertility medication used for inducing final oocyte maturation
Married for 6 years
2 years back, Intrauterine insemination (IUI) had been done in Muscat
private hospital but failed.
She doesn’t have any thyroid problems, no abnormal weight gain or weight
loss, no excessive hair growth.
Menstrual History:Menstrual History:
Her menarche age is 15 years. Menstrual periods were
irregular. The character of the flow is normal without
clots. No inter menstrual bleeding .Her LMP was on
She didn’t use any kind of contraception methods.
Past obstetric history
Marital historyMarital history
She is the first wife of her husband. She is married once. They sleep
together normally with adequate frequency. She does not have any
bleeding or dysuria with sexual intercourse.
Her husband is a 34 years old Omani man works as a office worker
in the educational ministry. His health condition is good. He has no
problems during intercourse and his work does not affect his
relationships with his wife.
Previous medical & surgical History
Related to her husband
Her father and mother are consanguinity.
Her father has DM & HTN.
Her sisters and brother had thyroid problems & under medication.
She is a teacher, living with her husband . She is not
smoking or alcohol consumer.
Unexplained primary infertility presenting with
ovarian hyperstimulation syndrom
Requirements for ConceptionRequirements for Conception
Production of healthy egg and spermegg and sperm
Unblocked tubesUnblocked tubes that allow sperm to reach the egg
The sperms ability to penetrateability to penetrate and fertilize the egg
ImplantationImplantation of the embryo into the uterus
Finally a healthy pregnancy
The inability to conceive following unprotected sexual
1 year (age < 35) or 6 months (age >35)
Affects 15% of reproductive couples
Men and women equally affected
Reproductive age for women:Reproductive age for women:
Generally 15-44 years15-44 years of age
20% of women have their first child after age 30
1/3 of couples1/3 of couples over 35 years have fertility problems:
Health of the egg declines
Health problems develop
With the proper treatment 85% of infertile couples can85% of infertile couples can
expect to have a childexpect to have a child
Primary infertilityPrimary infertility
a couple that has never conceived
Secondary infertilitySecondary infertility
infertility that occurs after previous pregnancy regardless of outcome
Causes of InfertilityCauses of Infertility
Anatomic defects of the female genital tract (30%)(30%)
Abnormal spermatogenesis (40%)(40%)
Male FactorMale Factor
40% of the cause for infertility
Sperm is constantly produced by the germinal epithelium ofSperm is constantly produced by the germinal epithelium of
the testiclethe testicle
Sperm generation time 73 days
Sperm production is thermoregulated
1° F less than body temperature
Both men and women can produce anti-sperm antibodiesanti-sperm antibodies
which interfere with the penetration of the cervical mucus
A. Gonadotropin Deficiency (Kallmann Syndrome)
failure of GnRH neurons to migrateGnRH neurons to migrate to the proper
location in the hypothalamus.
Kallmann syndromeKallmann syndrome is associated with midline defects
such as anosmia, cleft lip and cleft palate, deafness,
cryptorchidism, and color blindness.
Men can be fertile when given FSH and LH to stimulategiven FSH and LH to stimulate
sperm productionsperm production. Virilization can be obtained with
testosterone or human chorionic gonadotropin (hCG)
–C. Isolated FSH Deficiency
there is insufficient FSH production by the pituitary. Patients are
normally virilized, as LH is present. FSH levels are low. Sperm
counts range from azoospermia to severely low numbers
–D. Congenital Hypogonadotropic Syndromes
Prader-Willi syndrome Bardet-Biedi syndrome.
–A. Pituitary Insufficiency
Pituitary insufficiency may result from tumors, infarcts, surgery,from tumors, infarcts, surgery,
radiation, sickle cellradiation, sickle cell anemia.
–most common cause is prolactin-secreting pituitary adenoma.
–Elevated prolactin results in decreased FSH, LH levels andElevated prolactin results in decreased FSH, LH levels and
causes infertilitycauses infertility.
–Associated symptoms include loss of libido, impotence,include loss of libido, impotence,
galactorrhea, and gynecomastia.galactorrhea, and gynecomastia.
–C. Exogenous or Endogenous Hormones
1. Estrogens, GH, androgens, glucocorticoids, Hyper- andEstrogens, GH, androgens, glucocorticoids, Hyper- and
• Klinefelter syndrome (47,XXY)Klinefelter syndrome (47,XXY)
– most common genetic reason for azoospermia. classic triad:
small firm testes; gynecomastia; and azoospermiasmall firm testes; gynecomastia; and azoospermia.
– XX Male SyndromeXX Male Syndrome
– presents as gynecomastia at puberty or as azoospermia ingynecomastia at puberty or as azoospermia in
adultsadults. Average height is below normal, and hypospadiashypospadias is
common. Male external and internal genitalia are otherwise normal.
– XYY SyndromeXYY Syndrome
– Typically, men with 47,XYY are tall. Semen analyses show either
oligospermia or azoospermia.
–Causes of Male infertility - Gonadotoxins
– Sertoli and germ cells are extremely radiosensitive.
–Use of alcohol, cigarettes, caffeine, and marijuana may lead to
–Chemotherapy: toxic to actively dividing cells The most toxic
drugs are the alkylating agents such as cyclophosphamide.
– Systemic Disease - Causes of Male infertility
B. Liver Cirrhosis
C. Sickle Cell Disease
– Causes of Male infertility - Testis Injury
– Inflammation of testis tissue is most commonly due to bacterial
infection, termed epididymo-orchitis.
Testicular TorsionTesticular Torsion :
Ischemic injury to the testis secondary to twisting of the testis on the
spermatic cord. Torsion may result in inoculation of the immune
system with testis antigens that may predispose to later
Can invoke an abnormal immune response in addition to atrophy
resulting from injury. Both may contribute to infertility.
–Causes of Male infertility - Cryptorchidism
–Males with either unilaterally or bilaterally undescended testes are at
risk for infertility later in life. Prophylactic orchidopexy is generally
performed by 2 years of age
–A varicocele is defined as dilated and tortuous veins within the
pampiniform plexus of scrotal veins.
–Increased intratesticular temperature, reflux of toxic metabolites
–at least 25%-50% of male infertility has no identifiable cause
–Posttesticular Causes of Male infertility
–The posttesticular portion of the reproductive tract includes the
epididymis, vas deferens, seminal vesicles, and associatedepididymis, vas deferens, seminal vesicles, and associated
ejaculatory apparatusejaculatory apparatus
–1. Cystic fibrosis -
–98% of men with CF having missing
parts of the epididymis. In addition, the
vas deferens, seminal vesicles, and
ejaculatory ducts are usually atrophic, or
–2.Bacterial infections - Bacterial infections (E coli in men age
> 35) or Chlamydia trachomatis in young men) may involve the
epididymis, with scarring and obstruction.
–This is caused by an open bladder neck during
–Retrograde ejaculation may be due to causes such as
diabetes, bladder neck surgery, TURP, colon or rectal surgery,diabetes, bladder neck surgery, TURP, colon or rectal surgery,
multiple sclerosis, or spinal cord injury.multiple sclerosis, or spinal cord injury.
–Diagnosis is made by observing 10-15 sperm per high-
power field (HPF) in the postejaculatory urine.
–Disorders of Sperm Function or Motility
A. Immotile Cilia Syndromes
–B. Immunologic Infertility
Autoimmune infertility has been implicated as a cause of infertility in 10% of10% of
infertile couples..infertile couples..
– Autoimmune infertility may result from an abnormal exposure to sperm antigens
after, for example, Vasectomy, testis torsion, or biopsy, which then a pathologicVasectomy, testis torsion, or biopsy, which then a pathologic
immune response.immune response.
–Antibodies disturb sperm transport or normal sperm-egg interaction.
–Antibodies may cause agglutination of sperm, which inhibits passage,
– or may block normal sperm binding to the oocyte
–Disorders of Coitus - Causes of Male infertility
B. Sexual issues.
– Often treatable, problems with sexual intercourse Difficulties with
erection of the penis (erectile dysfunction), premature ejaculation,
painful intercourse (dyspareunia), or psychological or relationship
problems can contribute to infertility. Use of lubricants such as oils or
petroleum jelly can be toxic to sperm and impair fertility.
May not place the semen at the cervical os.
–D. Timing and Frequency
Simple problems of coital timing and frequency can be corrected by a review of
the couple’s sexual habits. An appropriate frequency of intercourse is every 2
days, performed within the periovulatory period.
ComponentsComponents ofof thethe infertilityinfertility historyhistory.
Fertility historyFertility history
Previous pregnancies (present and with other partners)
Duration of infertility
Previous infertility treatments
Sexual historySexual history
Timing and frequency
Medical historyMedical history
Systemic illness—diabetes, cancer, infection
Genetic diseases—cystic fibrosis, Klinefelter syndrome
Surgical historySurgical history
Pelvic, bladder, or retroperitoneal surgery
Transurethral resection for prostatism
Medication historyMedication history
Family historyFamily history
Social historySocial history
Occupational historyOccupational history
Exposure to ionizing radiation
Chronic heat exposure
Heavy metals (lead)
Laboratory Diagnosis of Male InfertilityLaboratory Diagnosis of Male Infertility
It may indicate the presence of infection, hematuria, glucosuria, or renal
disease, and suggest anatomic or medical problems within the urinary tract
Semen AnalysisSemen Analysis
•A normal semen analysis excludes male factor 90% of the time
Semen Analysis (SA)Semen Analysis (SA)
Obtained by masturbation
Provides immediate information
Density of the sperm
Abstain from coitus 2 to 3 days
Collect all the ejaculate
Analyze within 1 hour
Abnormal Semen AnalysisAbnormal Semen Analysis
Klinefelter’s (1 in 500)
(absence of the Vas
Exogenous (e.g. heat)
Cont. causes for abnormal SACont. causes for abnormal SA
Abnormal MorphologyAbnormal Morphology
Abnormal MotilityAbnormal Motility
Defect in sperm structure
Abnormal VolumeAbnormal Volume
Obstruction of ducts
Absence of vas deferens
Absence of seminal vesicle
Partial retrograde ejaculation
Hormone Assessment :Hormone Assessment :
A routine part of the initial evaluation is testing of specific serum hormone
levels, which usually includes FSH, LH, testosterone, and prolactin.
Ovulation occurs 13-14 times per year13-14 times per year
Menstrual cycles on average are 28 daysare 28 days with ovulation around day 14
dominated by the secretion of progesteronedominated by the secretion of progesterone
released by the corpus luteumreleased by the corpus luteum
Thickening of the endocervical mucusThickening of the endocervical mucus
Increases the basal body temperature (0.6° F)Increases the basal body temperature (0.6° F)
Involution of the corpus luteum causes a fall in progesterone and the
onset of menses
A history of regular menstruation suggests regular
The majority of ovulatory women experience
fullness of the breasts
decreased vaginal secretions
mild peripheral edema
slight weight gain
Diagnostic studies to confirm OvulationDiagnostic studies to confirm Ovulation
Basal body temperatureBasal body temperature
Endometrial biopsyEndometrial biopsy
Serum progesteroneSerum progesterone
After ovulation rises
Can be measured
Urinary ovulation-Urinary ovulation-
detection kitsdetection kits
Measures changes in urinary
Predicts ovulation but does
not confirm it
Basal Body TemperatureBasal Body Temperature
Excellent screening tool for ovulationExcellent screening tool for ovulation
Biphasic shift occurs in 90% of ovulating women
drops at the time of menses
rises two days after the lutenizing hormone (LH) surge
Ovum released one day prior to the first rise
Temperature elevation of more than 16 days suggests
Serum ProgesteroneSerum Progesterone
Progesterone starts rising with the LH surge
drawn between day 21-24
>10 ng/ml suggests ovulation
Sperm transport, Fertilization, &Sperm transport, Fertilization, &
The female genital tract is not just a passage:The female genital tract is not just a passage:
facilitates sperm transport
cervical mucus traps the coagulated ejaculate
the fallopian tube picks up the egg
Fertilization must occur in the proximal portion ofFertilization must occur in the proximal portion of
the tubethe tube
the fertilized oocyte cleaves and forms a zygote
enters the endometrial cavity at 3 to 5 days
Implants into the secretory endometrium for growthImplants into the secretory endometrium for growth
and developmentand development
Symptoms EvaluationSymptoms Evaluation
Irregular menstrual cycles
Increased vaginal secretions
Follicle stimulating hormone
Thyroid stimulating hormone
*Order the appropriate tests based on the clinical indications
day 3: FSH, LH, TSH, PRL ± DHEA, free testosterone (if hirsute)
day 21-23: serum progesterone to confirm ovulation
initiate basal body temperature monitoring (biphasic pattern)
post-coital test (Sims-Huhner's Test) cervical mucus after 2-6hrs of intercourse to look
for present motile sperm
• tubal factorstubal factors
HSG (can be therapeutic – opens fallopian tube)
laparoscopy with dye insufflation
• peritoneal/uterine factorsperitoneal/uterine factors
–Ultrasound scans can detect the development
of the follicle and its collapse after ovulation. Vaginal
ultrasound scan gives a much clearer picture than the
abdominal scan. The follicle is usually ready for
ovulation when it measures 1.8 - 2.5 cm in diameter.
An X-ray that evaluates
the internal female genital
architecture and integrity
of the system
Performed between the
day of the cycle
Diagnostic accuracy of
The endometrial cavity
Proximal 2/3 slender
Ampulla is dilated
Dye should spill promptly
–laparoscopy and dye test is the golden standard method to check the Fallopian tubes.
– Most infertile couples require a diagnostic laparoscopy for complete evaluation of their
Inadequate SpermatogenesisInadequate Spermatogenesis
Conservative management:Conservative management:
Intercourse every 1-2 days during periovulatory period
Women advice to lie on her bake at least 15 min after
coitus prevent rapid loss of semen from vagina
Use non-toxic lubricant
Smoking should be reduced or stopped.
Eliminate alterations of thermoregulation
MALE INFERTILITYMALE INFERTILITY
Clomiphene citrate is occasionally used for induction of
spermatogenesis (20% success)
Administration of bromocriptine for hyperprolactinemic
Injection of human menaposa gonadotropins (hMG) for
oligospermia and low motility of sperm.
In vitro fertilization may facilitate fertilization
Artificial insemination with donor sperm is often successful
Intracytoplasmic sperm injection
Administer ovulation inducing agents
Weight modulation — Ovulation dysfunction and subfertility may
occur in women who are far above or below ideal body weight
Combines and blocks estrogen receptors at the
hypothalamus and pituitary causing a negative feedback
Used in the treatment of polycystic ovarian syndrome.
Contraindication hepatic disease, ovarian cysts, hormone
dependent tumours, abnormal uterine bleeding of
Increases FSH production
stimulates the ovary to make follicles
Human menopause gonadotropin (hMG) (FSH &LH)
used for whom don't ovulate due to problems with the pituitary
gland, acts directly on the ovaries to stimulate ovulation.
Follicle-stimulating hormone (FSH) causes the ovaries to
begin the process of ovulation.
Gonadotropin-releasing hormone (Gn-RH) analog used
for whom don't ovulate regularly or ovulate before the egg is ready
Metformin use for PCOS, lower the levels of testosterone.
Bromocriptine for ovulation problems due to high levels of
Anatomic AbnormalitiesAnatomic Abnormalities
Lysis of adhesions
Surgery may be performed
If the fallopian tubes are beyond repair one must
consider in vitro fertilization
Management of unexplained infertilityManagement of unexplained infertility
The most efficient management is clomiphene citrate and
performance of intrauterine insemination (IUI).
If this has not resulted in pregnancy, it appears most useful to
subsequently perform in vitro fertilization (IVF).
The administration of clomiphene citrate is intended to achieve
ovulation induction or ovarian hyperstimulation.
Human chorionic gonadotropin (hCG) is given to trigger
ovulation, and the intrauterine insemination is performed within 2
days of hCG administration.
Ovarian hyper stimulation syndrome
Is a complication from some form of fertility medication
Causative medication: HCG used for inducing final oocyte
Prevention of OHSS:Prevention of OHSS:
monitoring of FSH therapy to use this medication judiciously, and by
withholding hCG medication.
Regarding dopamine agonists as prophylaxis.
Mild:Mild: conservative management with monitoring of abdominal girth,
weight, and discomfort on an outpatient basis until either conception or
ModerateModerate: bed rest, fluids, and close monitoring of labs such as
electrolytes and blood counts. Ultrasound may be used to monitor the size
of ovarian follicles
Aspiration of accumulated fluidAspiration of accumulated fluid
opioids for the painopioids for the pain
Assisted Reproductive TechnologiesAssisted Reproductive Technologies
Theses technologies help provide infertile couples with tools to
bypass the normal mechanisms of gamete transportation.
ART is a term that describes several different methods used
to help infertile couples. It involves removing eggs, mixing them
with sperm in the laboratory and putting the embryos back into a
Types of ARTTypes of ART
In vitro fertilization (IVF) often used when a woman's fallopian tubes are
blocked or when a man produces too few sperm.
Gamete intrafallopian transfer (GIFT) involves transferring eggs and sperm
into the woman's fallopian tube.
Intracytoplasmic sperm injection (ICSI) is often used for couples in which
there are serious problems with the sperm, older couples, or for those with failed IVF
attempts. In ICSI, a single sperm is injected into a mature egg. Then the embryo is
transferred to the uterus or fallopian tube.
is the deliberate introduction of semen into a female's vagina
It is the medical alternative to sexual intercourse, or natural insemination.
Intrauterine tuboperitoneal insemination
Emotional ImpactEmotional Impact
Infertility places a great emotional burden on the
The quest for having a child becomes the driving force of
the couples relationship.
It is important to address the emotional needs of these
Infertility should be evaluated after one year of unprotected
History and Physical examination usually will help to identify
If patients fail the initial therapies then the proper referral
should be made to a reproductive specialist.