By- Isha Thapa Magar

Master in Nursing (WHD)

TU,IOM
Etiology in Female Sub-fertility
Contd…
 Ovarian factors(30-40%)
• ovulatory dysfunctions
• Anovulation or oligo-ovulation
• Disturbed hypothalamo-pituitary-ovarian axis →no
ovulation, → no corpus luteum formation → absence of
progesterone → no secretory endometrium in second half
of cycle → oligomenorrhea or even amenorrhea.
• Decreased ovarian reserve
Contd..
 Luteal Phase Defect (LPD)
• Defective folliculogenesis→inadequate growth and function of
corpus luteum → short lifespan of corpus luteum < 10 days →
inadequate progesterone secretion → inadequate secretory
changes in endometrium → hinder implantation.
• Drug induced ovulation
• Decreased level of FSH and/or LH, elevated prolactin,
subclinical
• Hypothyroidism, older women, pelvic endometriosis,
• Dysfunctional uterine bleeding
 Decreased ovarian reserve

• ↓ed total no. of oocytes with ↑ed age of a woman→ ↓ed

inhibin B level & ↓ed anti mullerian Hormone level → ↓ed
ovarian reserve

 Luteinized Unruptured Follicular Syndrome (Trapped

Ovum)

• Pelvic endometriosis

• Hyperprolactinemia.
 Tubal factors (25-35%) causing obstruction of tubes
• Pelvic infections causing:
o Peritubal adhesions
o Endosalpingeal damage.

• Previous tubal surgery or sterilization.

• Salpingitis isthmica nodosa
• Tubal endometriosis
• Polyps or mucous debris within tubal lumen, or tubal spasm.
 Peritoneal factors:
o Peritubal adhesions,
o Deep dyspareunia too often troubles patient.

 Uterine factors (10%)

o Uterine hypoplasia,
o Inadequate secretory endometrium,
o Fibroid uterus,
o Endometritis
o Congenital malformation of uterus.
Cervical factors (5%)
 Anatomic defects
• congenital elongation of cervix
• uterine prolapse
• acute retroverted uterus
• Pinhole cervical os
• cervical polyp.
 Physiologic:
• Scanty mucus due to amputation, conization or deep
cauterization of cervix.

• Abnormal constituents cervical mucus include excessive,

viscous or purulent discharge

• Cervicitis

• Presence of antisperm or sperm immobilizing antibodies

Vaginal factors
• Atresia of vagina (partial or complete),

• transverse vaginal septum

• Septate vagina, or narrow introitus

• Dyspareunia

• Vaginitis and purulent discharge

Others
• Dyspareunia →poor coital function,
• Abnormal peritoneal fluid
• Abnormal systemic immune response
• Increased sperm phagocytosis by macrophages
• Fertilization and implantation failure
• Early miscarriage
 Combined factors
• Advanced age of wife beyond 35 years
• •
Infrequent intercourse
• Lack of knowledge of coital technique and timing of coitus
to utilize the fertile period
• •
Dyspareunia
• •
Anxiety
• •
Use of lubricants during intercourse→ spermicidal.
• •
Immunological factors.
Diagnosis
 History taking
• Age, duration of marriage, history of previous marriage

• Medical history → tuberculosis, sexually transmitted

disease, pelvic inflammation or diabetes.

• Surgical history → abdominal or pelvic surgery

→peritubal adhesions.

• Menstrual history → abnormalities of menstruation

ranging from hypomenorrhea—oligomenorrhea to
amenorrhea → disturbed hypothalamopituitary ovarian axis
 Previous obstetric history
• Number of pregnancies, pregnancy related complications,
puerperal sepsis
• Contraceptive practice IUCD use may cause PID.

 Sexual problems
• Dyspareunia, and loss of libido
• Loss of semen from vaginal orifice following coitus is
normal.
 Physical Examinations
 General examination
• Obesity or marked reduction in weight (BMI).
• Hirsutism, acne, underdevelopment of secondary sex
characters, features of PCOS and galactorrhea
 Systemic examination →hypertension, organic heart
disease, chronic renal lesion, thyroid dysfunction, and other
endocrinopathies.
 Gynecological examination
• Adequate hymenal opening, evidences of vaginal
infections, cervical tear or chronic infection, undue
elongation of cervix

• Uterine size, position and mobility, presence of unilateral

or bilateral adnexal masses —fixed or mobile with or
without tenderness and presence of nodules in pouch of
Douglas.

 Speculum examination abnormal cervical discharge.

Diagnostic Investigation of Ovulation
Factors
 Basal Body Temperature (BBT)
• There is “biphasic pattern” of temperature variation in
ovulatory cycle

• Rise of temperature is secondary to rise in progesterone

output following ovulation

• Progesterone is thermogenic.

• Increase in production and secretion of norepinephrine

which is also thermogenic

• Body temperature raised to 0.5° to 1°F following ovulation

• Drop temperature to about 0.5°F before rise and almost
coincides with either LH surge or ovulation.
• Rise actually occurs about 2 days after LH peak and
with a peripheral level of progesterone greater than 5
ng/ml.
• Patient is instructed to take her oral temperature daily
on waking in morning before rising out of bed.
• The temperature is recorded on a special chart.

• In cycles monitored with BBT, interval of highest fertility

spans 7-day interval immediately before midcycle rise in
BBT

• Coital timing can be optimized by suggesting intercourse on

alternate days beginning 7 days before earliest observed rise
in BBT and ending on the latest day it has been observed.
Fig. Biphasic BBT Chart
Urinary LH Excretion
• Generally known as ―ovulation prediction kits‖ or ―LH
kits,‖ are used to detect midcycle LH surge in urine.

• LH kits are available to detect midcycle LH surge.

• Ovulation usually occurs within 14–26 hours of detection

of urine LH surge and almost always within 48 hours.

• Interval of greatest fertility includes day LH surge is

detected and following 2 days.
• The test should be done on a daily basis.
• It is started 2–3 days before expected surge depending
upon the cycle length
• Ovulation predictor kits turn positive when urinary LH
concentration exceeds suggest ovulation.
• First morning void would seem an ideal specimen to
test
 Serum Progesterone Concentration
• Serum progesterone measurement is simplest, most common, objective
and reliable test of ovulatory function.

• Progesterone levels is below 1 ng/mL during follicular phase, rise

slightly on day of LH surge (1–2 ng/mL) and peak 7–8 days after
ovulation, and decline again over days preceding menses.

• A progesterone concentration less than 3 ng/mL indicate anovulation.

• Estimation of serum progesterone is done on day 8 and 21 of a cycle (28

days). An increase in value from less than 1 ng/ ml to greater than 6
ng/ml suggests ovulation
Cervical Mucus Study (Fern Test)
• During fertile window, cervical secretions at vaginal
introitus are thin, clear, slippery and with a great elasticity
property stretching up to 10 cm, while secretions at other
times of menstrual cycle are dry and sticky.

• Volume of cervical mucus peaks 2 to 3 days prior to

ovulation, thus identifying higher day-specific probabilities
of conception.
Fig. Mucus secretion during a menstrual cycle
 Serum Estradiol

• Serum estradiol attains peak rise approximately 24

hours prior to LH surge and about 24–36 hours prior

to ovulation.
 Endometrial Biopsy
• Biopsy is to be done on 21st–23rd day of the cycle
but in irregular cycle, it is done within 24 hours of
period.

• Evidences of secretory activity of endometrial glands

suggest ovulation and functional integrity of corpus
luteum.
Transvagnial Sonography (TVS)
• TVS during mid cycle measure maturation of Graafian follicle (18-
20mm).

• It is particularly helpful for confirmation of ovulation following

ovulation induction, artificial insemination, and in vitro fertilization.

• This requires daily ultrasonic visualization of ovaries from the 10th to

16th day of menstrual cycle.

• It is noninvasive, accurate and safe.

• It monitors follicular maturation for ovulation, pelvic pathology and

endometrial thickening.
• Follicle grows at rate of 1–2 mm daily to reach 20 mm or more
when follicular rupture and ovulation occur at midcycle.
• Sudden disappearance of follicle, presence of free fluid in
pouch of Douglas and growth of corpus luteum.
• Endometrial thickness of 8–10 mm is normal response of
endometrium to progesterone.
• A lesser thickness indicates corpus luteal phase deficiency
(CLPD)
 Laparoscopy

• Laparoscopic visualization of recent corpus luteum or

detection of ovum from aspirated peritoneal fluid

from pouch of Douglas is only direct evidence of

ovulation.
Diagnostic Investigation for Tubal
Factors
 Hysterosalpingography (HSG)
• HSG is done after menses but prior to ovulation
between cycle days 7 and 12 as endometrium is
thinner in proliferative phase and to avoid
potential pregnancy .
• Patient is premedicated 30 to 60 minutes prior to
procedure with ibuprofen.
• Lidocaine injected intracervically for pain relief.
 Contd..
• With patient in dorsal lithotomy position, either a metal
cannula or a balloon catheter is inserted through cervix
and past internal cervical os.
• Contrast dye is then injected under fluoroscopy to
visualize uterine cavity, fallopian tube architecture,
and tubal patency
• HSG is highly effective for bilateral tubal patency and
bilateral tubal occlusion but effectiveness drops for
unilateral tubal patency reporting false-positive.
 Laproscopy

• Laparoscopy is gold standard for diagnosing tubal

and peritoneal disease.

• It allows visualization of all pelvic organs and

permits detection and treatment of uterine fibroids,

peritubal and periovarian adhesions, and

endometriosis.
 Contd..
• Abnormal findings on HSG can be validated by
direct visualization on laparoscopy using
chromopertubation, through transcervical
installation of a dye to directly visualize tubal
patency and fimbrial architecture

• Laparoscopy also show a false-positive rate of

11% for proximal tubal occlusion.
 Diagnostic Investigation of Uterine
factors
• Hysteroscopy

• Hysterosalpingogram

• Transvaginal Ultrasound

• Sonohysterosalpinography

• Magnetic resonance Imaging

 Hysteroscopy
• Hysteroscopy is gold standard for uterine cavity
evaluation as it allows for direct visualization.

• Procedure involves insertion of an endoscope

through cervical canal into uterine cavity and
instillation of distension media to allow for
visualization.
 Contd…

• It is done during early- to mid-follicular phase

of cycle.
• Disadvantages of it include poor visualization
when uterine bleeding is present and the
inability to evaluate structures outside uterine
cavity, myometrium and adnexa.
 Magnetic Resonance Imaging

• Pelvic MRI is considered gold standard for

imaging and is useful for diagnosing
rudimentary uterine horns and detecting large
or multiple fibroids.
 Sonohysterosalpinography

• It is noninvasive procedure and no radiation exposure.

• Normal saline is pushed within uterine cavity with

foley catheter. Catheter balloon is inflated at the level
of cervix to prevent fluid leakage. Ultrasonography of
uterus and fallopian tubes are done.

• It is used for diagnosis of uterine malformations,

polyps and tubal patency.
Diagnostic Investigation of Cervical
factors
 Postcoital Test (PCT)
• Also known as Sims-Huhner test
• This test is done to assess quality of cervical mucus and
ability of sprem to survive in it.
• A couple is requested to have intercourse on midcycle of
menstruation and within a few hours, sample of the
cervical mucus collected from the cervical os.
• Thus, test for diagnosis of cervical factors for infertility is
no longer recommended due to improper timing.
 Management of Female Sub-fertility
• General Management
• Treatment of Ovulatory Dysfunction
• Treatment of Luteal Phase Defect
• Treatment of Luteinized Unruptured Follicle
• Surgery
o Tuboplasty
o Uterovaginal Surgery
• Cervical factors
• Immunological Factor
• Unexplained Infertility
 Contd..

General
• Psychotherapy to improve emotional causes, if any.

• Reduction of weight in obesity as in PCOS cases is

essential to have a good response of drug therapy for
induction. This facilitates spontaneous ovulation
 Treatment of Ovulatory Dysfunction

Drugs

1. Stimulation of ovulation:

™
Clomiphene citrate (CC )

o Pts with Normogonadotropic- normoprolactinemic,

normal cycles with absent or infrequent ovulation.

 Contd..
o CC 50 mg on days 2- 5 or days 5-9in initial. Dose is

↑ed in 50 mg to maximum 250 mg daily, if ovulation

is not induced by low dose.

 hCG : is given incase of anovulation due to failure of

LH surge. hCG 5000IU-10000IU is administered usually
7 days after last dose of CC therapy.

 Clomiphene citrate (100mg on days 2-5) plus FSH (1-2

amps starting on day 8)
 hMG (human menopausa lgonadotropin) is a mixture of FSH
and LH

• Use in pts with low oocyte , non-ovulatory factors related sub-

fertility, Hypogonadotropic hypogonadism,„Clomiphene failed or
resistant cases.

• Dose schedule

o hMG stimulates follicular growth with a variable dose schedule

starting with a low dose (75 IU IM/day)

o Started on D2 to D5 of cycle &continued for 7–10 days ™

.
• Follicular growth (follicular no. & size) is monitored
with serum estradiol estimation & transvaginal
sonography (TVS).

• Serum estradiol level of 500–1500 pg/ml, follicular

diameter of 18–20 mm and Endometrial thickness >
8–9 mm are optimum.
 Contd....
• When above optimum levels are obtained, 5000-
10000 IU of hCG is administered 1M to induce
ovulation.

• ™™
Ovulation is expected to occur, approximately 36
hours after hCG administration.

• Couple advised for timing of intercourse or

insemination (ART) accordingly.
2. Correction of Biochemical Abnormality
• ™
Hyperinsulinemia (insulin resistance) Metformin (insulin
sensitiser)
• ™
Androgen excess - Dexamethasone
• ™
Prolactin raised - Bromocriptine
3. Substitution therapy
• ™
Hypothyroidism - Thyroxin
• ™
Diabetes mellitus - Antidiabetic drugs
 Treatment of Luteal Phase Defect

• Treatment of Luteal Phase Defect

• Natural progesterone as vaginal suppositories 100
mg thrice daily starting from day of ovulation is
effective. It should be continued until menstruation
begins.
• If menstruation fails to appear after 14 days,
pregnancy test is to be done. If the test is positive, it
should be continued up to 10th week of pregnancy.
 Treatment of Luteinized Unruptured Follicle
(lUF)

• Defective folliculogenesis or inadequate LH surge

is corrected with:
– hCG 5000–10,000 IU, IM

– Administration of ovulation inducing drugs in

follicular phase followed by ovulatory hCG 5000–
10000 IU.

– Bromocriptine therapy for hyperprolactinemia.

 Surgery

• Tuboplasty is done for removal of peritubal

adhesions and tubalblock in tubal factors

subfertility.
Types of Tuboplasty Operation
 Uterovaginal Surgery
• Following types of surgery is done according to problems.
o Myomectomy is done in submucosal fibroid.

o Metroplasty to remove septum or unification operation may

be tried.

o Adhesiolysis with insertion of IUCD

o Enlargement of the vaginal introitus removal of vaginal

septum causing dyspareunia results in improvement of fertility.

o Endometrial polyps: Hysteroscopic polypectomy.

 Cervical factors
• Cervical mucus quality can be improved by conjugated
estrogen 1.25 mg orally daily starting on day eight for
5 days.

• Treat infections by doxycycline 100 mg twice daily for

14 days both partners.

• Cervical factor when cannot be treated, is overcome by

ART procedures like lUI, IVF or GIFT.
 Immunological Factor
• In presence of antisperm antibodies in cervical
mucus, dexamethasone 0.5 mg, HS in follicular
phase is given.

• No benefit of such treatment in antisperm antibody

positive patients, ART (IUI or IVF or ICSI) is
recommended.
 Unexplained Infertility

• Recommended treatment for unexplained

infertility are induction of ovulation, lUI,
Superovulation combined with lUI and
Assisted Reproductive Technology