Download Female infertility

Female infertility
Female factor is responsible for 55% of all fertility problems. It could be due to:
1. Ovulation factors
Ovulation process is under control of the pituitary gland which is located in the base of the brain.
In normal conditions, the hypothalamus sends signals to the anterior pituitary to release follicle
stimulating hormone (FSH) and luteinizing hormone (LH), which in turn triggers the ovary to
mature and release the egg. Any disturbance in the hormonal system can affect normal ovulation
and prevents the release of immature egg from the ovary. Ovulation problems account for 20%
of all infertility cases.
Hypothalamic-Pituitary Ovarian Axis
The most common ovulatory disturbances are:
 Polycystic ovarian syndrome (PCOS): It is a common medical condition (one in ten women
has PCOS), symptoms include history of missed or irregular periods, acne, oily skin, dandruff,
over weight (high body mass index), increased hair growth (on the face, chest, abdomen, back
and thighs) and infertility. Although the typical PCOS patient is obese, having increased body
hair, and irregular periods, some patients may be thin, with no complaints except irregularity of
menstrual cycle. Some patients may be diagnosed at their first visit to the infertility clinic by
ultrasound with no symptoms. Ultrasound scan of the ovaries shows many small cysts, chain
like in appearance. PCOS is associated with endocrinological abnormalities in particular
elevated levels of LH, prolactin, androgens (testosterone and androstenodione) and insulin
resistance. Women with polycystic ovaries require careful management to achieve follicular
maturation in an environment free from disturbed hormonal levels in order to enhance
fertilization and pregnancy outcome. Management includes weight reduction, use of insulin
sensitizers (i.e. Metformin) and cycle regulation by oral contraceptives or progesterone tablets
in addition to the use of fertility drugs (Clomiphene citrate, follicle stimulating hormones,
human chorionic gonadotrophin/ HCG) and in vitro fertilization (IVF) using these drugs.
 Poor ovarian reserve; Ovarian reserve is an estimate of supply of oocytes remaining in the
ovary and is closely associated with reproductive potential. This oocyte supply begins to be
depleted even before birth, continues until menopause with accelerated rate of loss at around
37 years.
Factors affecting ovarian reserve
- Female age is an important factor in fecundity but it is not very exact in predicting
reproductive potential. Some women will be unable to conceive in their thirties while others
become pregnant in their forties.
- FSH and Estradiol: FSH levels tend to increase with age. Pregnancy rates are higher in
women whose FSH levels are below 15 IU/L and Estradiol below
50 pg/ml.
- Smoking accelerates the diminished ovarian reserve process.
Etiology of poor ovarian reserve
- Idiopathic
- Natural decline of ovarian reserve due to age.
- Genetic factors
- Autoimmune disorders
- Iatrogenic, e.g., due to radiation or chemotherapy
The assessment of ovarian reserve is valuable for determining stimulation protocols and
predicting ART outcome. In invitro fertilization (IVF), the association of poor ovarian response
with cycle cancellation and significant decline in success rate is well known.
Ovarian reserve tests
- Day-3 serum FSH concentration: FSH has been shown to be a better predictor than age.
- Basal FSH/LH ratio
- Day-3 serum Estradiol concentration. It is important to correlate basal FSH value with
Estradiol level. Basal Estradiol values above 50 pg/ml decrease FSH levels through negative
feed back on pituitary gland.
- Day-3 serum inhibin B concentration. Decreased inhibin B are found in women with
diminished ovarian reserve despite having non elevated FSH concentrations and is an earlier
marker for poor reserve than FSH.
- Serum anti-mullarian hormone (AMH) level: AMH is a marker for ovarian reserve that can
be estimated at any time of the cycle.
- Ovarian volume: At 40 years the ovaries tend to decrease in size and decrease further after
menopause.
- Antral follicle count (AFC): is a predictor of number of oocytes collected in an IVF program
as well as the cancellation rate.
 Increased prolactin hormone level (Hyperprolactinemia); this is a condition when there is
increased prolactin secretion from the anterior pituitary gland in the brain. Normal prolactin
level is 1-20ng/ml, elevated values above this level may lead to galactorrhea (milky discharge
from the breast not related to pregnancy and lactation) and infertility. Regarding infertility,
hyperprolactinemia inhibits ovulation leading to menstrual irregularities as well as amenorrhea
in addition it interferes with corpus luteal function leading to corpus luteum deficiency. This
condition may be due to pituitary tumour (micro and macro-adenoma) and certain medications
(Cimetidine, Fluoxetine, Phenothiazines). Treatment is medical by drugs that inhibit the
pituitary prolactin secretion like Bromocriptine (Parlodile) and Cabergoline (Dostinex).
Surgical intervention is indicated in few cases.
 Thyroid gland dysfunction; in which the secretion of thyroid stimulating hormone (TSH) is
disturbed. Both elevation (hyperthyroidism) and reduction (hypothyroidism) of TSH can affect
ovulation leading to impairment of fertility. Treatment is to control and regulate this by giving
specific hormonal therapy.
2. Pelvic factors;
Involve pelvic adhesions which occur in patients with endometriosis, pelvic inflammatory
diseases, and abdominal/pelvic surgeries. With time, these patients may develop bands of scar
tissue that binds organs together, and disturb their fertility potential.
 Endometriosis; in this condition, endometrial cells of the uterine tissue grow and implant
outside the uterus. These implants grow, shed and bleed in synchronization with the lining of
the uterus each monthly cycle, eventually resulting in inflammation and scarring in the pelvis
and may form an endometrioma (chocolate cyst) in the ovary. These implants are mostly found
on the ovaries, fallopian tubes, outer surface of the uterus, intestine, pelvic cavity, and even
cervix and vagina impairing normal function. Endometriosis is thought to be caused by
retrograde menstruation. When the tissue infiltrate the myometrium (wall of the uterus), the
condition is known as adenomyosis. Symptoms include pelvic pain, dysmenorrhoea (painful
menstrual period) usually worse immediately before and at the beginning of menstruation and
dyspareunia (painful intercourse). Endometriosis is found in about 20% of infertile women
with unexplained infertility prior to laparoscopy. Symptoms usually resolve in pregnancy and
after menopause. Treatment is either conservative by down regulation of ovarian function with
specific medications as gonadotrophin releasing hormone agonists, Danazole and oral
contraceptives, or through surgical approach where endometriosis implants and cysts are
removed by laparoscopic surgery.
 Pelvic inflammatory disease (PID); refers to infection of the female reproductive tract mostly
due to sexually transmitted diseases (i.e Chlamydia, gonorrhoea). This may end in block and
damage of the fallopian tubes in addition to pelvic scarring that affects ovarian function.
Symptoms include complaints of recurrent fever, pain, pelvic discomfort, vaginal discharge
and could be asymptomatic. PID can develop into permanent damage of the female
reproductive organs if not given the necessary treatment.
 Abdominal/pelvic surgeries; adhesions are formed in 15% of patients following abdominal and
pelvic surgeries. These surgeries include hernia repair, colorectal surgeries and gynaecological
surgeries. Adhesions can lead to 15-20% of infertility cases. IVF program is needed in a high
proportion of these to assist conception.
3. Tubal factors;
Open healthy fallopian tubes are important for conception. Tubal block or unhealthy tubes can
be due to:
 Sexually transmitted diseases (STD); the most common are Chlamydia and Gonorrhea. They
can lead to tubal infection which results in infertility. The risk of ectopic pregnancy
(implantation of embryo outside the uterus) increases with recurrent tubal infection as tubal
damage will prevent the egg to make its way through the fallopian tube to implant in the uterus
therefore leading to ectopic pregnancy.
 Endometriosis, ectopic pregnancy, uterine fibroids and previous tubal ligation can lead to
scarring and block of the fallopian tube. Tubal blockage is diagnosed by hysterosalpingogram
(HSG) or laparoscopy.
 In tubal infertility, laproscopic surgery to open tubes if possible may have a role in
management. However, the most effective treatment is IVF.
4. Uterine factors
 Fibroids are benign tumours in the wall of the uterus and tend to increase the incidence of
miscarriage and impair fertility by blocking the fallopian tubes or affecting embryo
implantation if they are occupying the uterine cavity. It is common in women over 35 years. It
may pass asymptomatic and discovered by ultrasound examination or the patient may complain
of heavy bleeding during period. Myomas are classified according to their location as:
- Subserosal: which develop in the outer portion of uterus and continue to grow outward. It
causes symptoms due to their size only.
- Intramural: grow within the uterine wall and cause bulk symptoms and heavy periods. They are
the most common of fibroids.
- Submucosal: develop under the lining of the uterine cavity. They are the least common of all
fibroids and cause heavy prolonged menstrual periods.
- Pedunculated: occurs when fibroids grow on a stalk.
Myomectomy is recommended in submucous fibroids, while with intramural and subserous
ones, the decision depends on the size of the myoma and related symptoms.
 Endometrial polyps; are small, soft, growths in the lining of the uterus. Endometrial polyps
usually grow very slowly and rarely turn cancerous. However, some women with endometrial
polyps will have difficulty becoming pregnant. Often, symptoms of endometrial polyps do not
occur when the polyps are small. However when they do occur, symptoms include:
- Spotting between menstrual periods
- Pelvic cramps
- Heavy or prolonged menstrual periods
- Bleeding during hormonal therapy
Endometrial polyps can be surgically removed through hysteroscopy. After the polyp is
removed, the patient can return to work in a few days. The most common side effect is a little
spotting for a few days.
 Uterine anomalies; it is estimated to be found in 2-4% of all women and have been detected in
15-25% of women with recurrent pregnancy loss and 3.5% of infertile women. The clinical
evaluation of infertile /sub-fertile women to rule out uterine abnormalities is important as
uterine malformations are detected in 0.16% of fertile women as compared to 3.5% prevalence
in infertile women showing a deep casual relationship between the two events.
Types of uterine anomalies:
1.Hypoplasia/agenesis: this is lack of vagina, cervix, uterus and part of the fallopian tubes.
These anomalies are commonly assosciated with urinary tract anomalies.
2.Unicornuate: when one of the mullerian ducts fails to develop, a single horn (banana shaped),
uterus develops from the healthy mullerian ducts. In 65% of women the remaining duct may
form an incomplete rudimentary horn.
3.Didelphus: a double uterus results from complete failure of the two mullerian ducts to fuse
together. So each duct develops into a separate uterus each of which is narrower than the
normal one. These two uteri may each have a cervix or may share a cervix. In 67% of cases a
didelphus uterus is assosciated with two vaginal separated by a thin wall.
4.Bicornuate: it is the most common congenital anomaly resulting from failure of fusion of
ducts at the top. Complete bicornuate uterus results in two separate single horn uterine bodies
having one cervix. In partial bicornuate uterus there is a single cavity at the bottom with
single cervix but it branches into two distinct horns at top.
5.Septate: could be complete separating the entire uterus into two single horned uteri which
share a single cervix or incomplete when septum is present only in upper part of cavity.
6.Arcuate: this type is normal in shape with a small, midline indentation in the uterine fundus.
This is given a distinct classification because it does not seem to have any negative effect on
pregnancy except for Luteal phase defect.
7.Dethylstilbestrol(DES): drug related exposure during fetal life will result in small or Tshaped uterus with increased risk of pregnancy in fallopian tubes.
 Int
rau
ter
ine
ad
he
sio
ns
(A
sh
er
ma
n
syndrome); also called “uterine synechiae”. The cavity of the uterus is lined by the
endometrium. Trauma to this lining typically occurs after a dilatation and curettage (D&C),
pelvic surgeries as caesarean sections, genital tuberculosis, and chronic endometritis can lead
to a development of intrauterine scars resulting in adhesions which can obliterate the cavity to
a varying degree. In the extreme, the whole cavity could be scarred and occluded. Depending
upon the degree of severity, Asherman may result in secondary amenorrhea, infertility,
repeated miscarriages, and pain from trapped blood and high risk of ectopic pregnancy. There
is evidence that left untreated; the obstruction of menstrual flow resulting from scarring can
lead to endometriosis. Fertility can be restored by dissection of adhesions (adhesiolysis)
through hysteroscopy. Laparoscopy can be used in addition as a protective measure against
uterine perforation. Sometimes a balloon stent ( Folley catheter or Cook stent) filled with saline
is inserted in the uterus up to three weeks to keep the walls of the uterus apart as they heal to
prevent the reformation of adhesions.
Hormonal therapy with synthetic or conjugated oestrogen is usually prescribed following
surgery to stimulate the endometrial growth, thereby preventing the walls of the uterus from readhering. Follow up tests include hysterosalpingogram (HSG) or hysteroscopy to ensure that
scars have not reformed.
5. Cervical factors
Some cervical conditions like immunological factors (anti-sperm antibodies) and cervical
surgeries may contribute to infertility but rarely considered as the only cause. Post coital test
(PCT) can determine these factors. This test evaluates the cervical mucous, the sperm and their
interaction. It is performed as approximate to the day of ovulation as possible (2-18 hrs after
intercourse), a sample of cervical mucous is taken and immediately examined under the
microscope. With positive test, mucous should be of good quality (clear, watery, abundant and
stretchable) with adequate number of motile sperm present and moving progressively forward.
This test is painless, done in the clinic and needs just few minutes. If PCT is unfavourable, there
could be a problem with sperm production, its delivery to the vagina or an immunological factor.
If mucous quality is poor or quantity is inadequate, this could be due to the test performance at
the wrong time of menstrual cycle or due to prior cervical surgery.