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ASSISTANT PROFFESOR of
Obstetrics & Gynecology
Cairo university
Infertility II
Ovarian factor of
infertility
Definition of ovulation:
It is the rupture of a fully mature Graafian follicle with
release of the oocyte surrounded by the crona radiata and
the zona pelluicda to the peritoneal cavity, to be picked up
by the fimbrial end of the tube.
Mechanism: Ovulation is controlled by 2 mechanisms.
Central:
The secretion of F.S.H. and a little amount of L.H. from the anterior
pituitary under the control of hypothalamus causes follicles in the
ovary to ripe and to secrete estrogen.
The resulting high level of estrogen by a positive
feedback mechanism on L.H. secretion causes L.H. surge,
which causes ovulation and corpus luteum formation
(acts through prostaglandins).
Local:
Increased tension of the fluid inside the follicle.
Increased enzymatic activity of the follicular fluid (proteolytic
activity).
infertility
Ovulation and its
disorders
Symptoms: all the symptoms are only suggestive for the
occurrence of ovulation
1- Regular cycle: it is strongly suggestive of monthly
ovulation
2- Ovulation pain (mittelschmerz):
It is a dull aching pain experienced in one illiac fossa at time
of ovulation, it is caused by irritation of the peritoneum by the
fluid of the Graafian follicle.
3- Ovulatory bleeding: (ovulatory spotting):
Spotting vaginal bleeding may occur at time of ovulation.
4- Ovulatory discharge (cascade):
Some females develop increase in the normal vaginal
discharge at the time of ovulation due to increase of the level
of estrogen hormone to maximum just before ovulation with
activation of the cervical glands.
Ovarian factor of infertility
• 5- Premenstrual tension:
• The presence of premenstrual tension
especially mastalgia (breast pain and
tenderness) is a reliable evidence that ovulation
has occurred during that particular cycle.
• 6- Spasmodic dysmenorrhea: occurs only
with ovulatory cycles.
Ovarian factor of infertility
• Assessment of ovarian factor:
• A- To assess ovarian reserve, an early follicular
(day 1-3 of the cycle) gonadotropin level by
serum FSH and LH is essential, an LH: FSH
ratio of 2:1 or more indicated underlying PCOS.
• B- Assessment of the thyroid functions,
prolactin level and androgen profile is
necessary in women with irregular cycles.
Investigations to diagnose ovulation
1- Basal body temperature
2- Changes In the vaginal smear: Progesterone
effect.
3-Changes in cervical mucus:-ve thread &
ferning test
4- Premenstrual endometrial biopsy P.E.B.:
secretory changes, detection of L.P.D and T.B
endometritis.
5- Hormonal assay: serum progesterone in the
2nd half, pregnandiol in urine, detection of L.H.
peak.
Basal body temperature
chart
Simplest test to detect
A ovulation
Progesterone has a
thermogenic effect.
the patient is instructed to
record daily oral
temperature prior to getting
B out of bed
During the follicular
phase the temperature
is relatively tow, rise of
the body temperature
by 0.2 to 0.5 °c during
the luteal phase is an
indication of ovulation.
A biphasic temperature
chart suggesting
Changes In the vaginal
smear
Before ovulation:
A Estrogenic smear: cells
polyhedral, flat edges, small
pyknotic nuclei and acidophylic
cytoplasm (stains pink).
(Superficial cells). Maturation
index 0, 30 and 70 (parabasal,
intermediate and superficial
cells)
After ovulation:
B Progesterone effect: Cells
collected in clusters, folded
edges, vesicular nuclei, the
cytoplasm is basophilic with
lecuocytic infiltration in-between
(intermediate cells) Maturation
index 0, 70 and 30.
Changes In the cervical
• mucus
3-Changes in cervical mucus
• Before ovulation
• Positive thread test (spinnebarkeit test): the cervical
mucus can be thrown to a thread that reach maximum
of 7-10 cm. This test is carried by putting one drop of
the cervical mucus between two glass slides and then
separates them.
Positive ferning test (Arborization test): the cervical
mucus when left to dry; deposits of crystals of sodium
and potassium chloride arrange in a characteristic
pattern which is similar to palm leav
• After ovulation: Negative thread and ferning test.
Changes in cervical
mucous
+ ve thread
(spinbarkiet) test just
before ovulation
Rec. FSH
Rec LH
GnRH (pulsatile).
GnRHa (intranasal-S.C- I.M)
Oocyte mature
Clomiphene Gonadotrophin 38 hrs
100 mg day2 stimulation from
for 5 days day 4 to day of
HCG
HCG Leading follicle > 18mm
Purified F.S.H. ( pureagon
-Metrodin)
Specially used in cases of P.C.O. having
abnormally high L.H so the use of
unpurified F.S.H may lead to premature
luteinization of the follicle.
One ampoule contains 75 I.U of F.S.H. 1 I.U.
L.H. Recently highly purified (Recombinant
F.S.H) containing F.S.H only is available.
Gonadotropic releasing
hormone (Gn.R.H.) or
(L.H.R.H.)
Nature: It is a decapeptide synthetic GnRH.
Mode of action: it increases gonadotropine
secretion from the pituitary.
Selected cases
Hypogonadotropic hypogonadism of
hypothalmic origin e.g Kallman’s syndrome.
Failure of ovulation or occurrence of
complications in response to clomiphene or
H.M.G.
Gonadotropic releasing
hormone (Gn.R.H.) or
(L.H.R.H.)
Dose and administration
Pulsatile administration by I.V or S.C routes
through the use of a portable infusion pump.
The inter-pulse time intervals are 60-120 minutes
(90 minutes on the average), when the follicle
become mature 10.000 I.U of HCG is given I.M or
change the inter-pulse interval of (G.N.R.H) to
every 4 hours.
Gonadotropic releasing
hormone (Gn.R.H.) or
(L.H.R.H.)
Side effects
Minimal and generally confined to local
phenomena (irritation or inflammation).
Allergic reaction being a synthetic
protein.
No hyperstimulation as Gn-Rh
produces down regulation of its own
receptors.
Gondotropic releasing hormone
[Gn-R.H or LH-RH] analogue
Given continuously
subcutaneous every day or
intranasal every 4 hours causes
suppression of endogenous
gonadotropic secretion (in cases
of with persistent high LH level
or in cases with premature LH
peak as cases of P.C.O) then,
H.M.G and H.C.G are given to
induce ovulation.
Bromocryptine
Nature: lysergic acid derivative,
dopamine agonist.
Mode of action: Binds to dopamine
receptors in the anterior pituitary thus
decreasing prolactin.
Selected cases: Cases associated with
galactorrhea or hyperprolactinaemia.
Dose and administration: 2.5 mg one to
two times orally daily with meals.
Side effects: G.I.T irritation (common),
Faintness, Hallucination, dizziness and
fatigue
Other drugs
Thyroid extract: In cases of
hypothyroidism.
Cortisone: In cases of Addison’s disease,
adrenogenital syndrome and in some
cases of P.C.O. especially associated with
Hirsutism.
Hyper stimulation
syndrome
Excessive enlargement of the ovary with multiple cystic
formation. It occurs with H.C.G injection after clomid or F.S.H.
therapy especially in young and lean P.C.O cases.
Clinical manifestations: abdominal pain (ovarian
enlargement), abdominal distension (ascites), nausea,
vomiting, edema, oliguria and chest pain (pleural effusion
and arrhythmias)
Signs: weight gain, edema, hypotension, abdominal
enlargement
Risks: D.V.T, rupture of the ovarian cyst causing acute
abdomen, liver dysfunction, respiratory distress, renal
failure and adnexal torsion.
Prevention: avoid giving H.C.G if the ovaries are cystic
or Estradiol level above 2000pg/ml, follicular aspiration
Treatment: bed rest, avoid rough abdominal or pelvic
examination, correction of hypovolemia and electrolyte
imbalance, I.V albumin, anti-coagulant therapy in DVT,
diuretics are contraindicated and may be aspiration of the
peritoneal and pleural fluid.
Surgical treatment
Bilateral wedge resection of the ovaries
in cases of P.C.O .This operation is usually
followed by periovarian and peritubal
adhesions that may result in infertility itself
(out of use). It can be done laparoscopically to
decrease post-operative adhesions.
Ovarian electrocautery (ovarian drilling)
can be done laparoscopically in cases of
P.C.O., it consists of multiple cauterization of
the external surface of the ovary. It is associated
with decline in testosterone and L.H. levels, increase in F.S.H.
levels, resumption of ovulation and increase chances of
pregnancy But carries the risk of ovarian failure
or the development of peritubal adhesions in
some cases.
Ovarian drilling
Multiple puncture
made to the surface of
the ovary.
Luteal phase defect
Definition: it is inadequate secretory endometrium
due to insufficient secretion of progesterone by
the corpus luteum or premature cessation of
corpus luteum activity (short luteal phase less
than 11 days).
Etiology: Inadequate release of F.S.H., abnormal
F.S.H./L.H. ratio at time of ovulation,
hyperprolactinemia and during induction of
ovulation or the use of synthetic progestogen
Symptoms: Infertility or Habitual abortion in the
1st trimester (may be silent early abortion).
Luteal phase defect
Diagnosis: (continued)
1- Dated premenstrual endometrial biopsy
shows lag of 2 days or more.
2- Serum progesterone on day 22 of the
cycle (between 3-10 ng/ml). Estimate serum
prolactin at the same time (normally 4-20 nanogram /ml) as
some cases are associated with hyperprolactinanemia.
3- Basal body temperature may denote a
short luteal phase (8 days or less).
Luteal phase defect
Treatment of (continued)
luteal phase defect:- Progesterone
1.25 mg I.M daily (or progesterone vaginal
suppositories 25 mg twice daily) in the 2nd half
of the cycle (2-3 days after ovulation). If
pregnancy occurs as detected by estimation of
serum beta subunit of human chorionic
Gonadotropin before the expected time of
menstruation, progesterone treatment should
continue during the first trimester until the
placental formation.
H.C.G in the second half of the cycle 5000 I.U.
I.M every 3 days for 5 doses.
Bromocreptin: in cases of hyperprolactinemia
Luteinized unruptured follicle syndrome
Definition: failure of rupture of the mature
follicle followed by luteinization of its cells
with progesterone secretion
This is a rare cause of infertility. Basal
body temperature, endometrial biopsy and
serum progesterone are similar to those
found in ovulatory cycle but the follicle
does not rupture and the oocyte is still
inside the un-ruptured follicle. This is
diagnosed by laparoscopy and ultrasound
performed 3-5 days after the L.H. peak.
These cases are treated by clomiphene
citrate and H.C.G. or H.M.G. and H.C.G.