Pharmacological Management of Infertility

Pharmacology (CBME) Number PH 1.40 :Describe mechanism of action, types, doses, side
effects, indications and contraindications of 1. Drugs
used in the treatment of infertility

1. Sawai Man Singh Medical College, Jaipur
PHARMACOLOGICAL
MANAGEMENT OF INFERTILITY:
DIAGNOSIS AND TREATMENT
by
Dr. Shivankan Kakkar, MD

2. INFERTILITY
Infertility is defined as inability to achieve
pregnancy after unprotected and well-
timed intercourse over a sustained period
of time:
12 months in a woman in a woman
age <35
6 months in a woman age ≥35

3. A 35-year-old woman comes to the
gynecologist’s office complaining of
infertility for 1 year.
There is no previous history of pelvic
inflammatory disease, and she previously
used oral contraceptive pills for 6 years.
Pelvic examination is normal.
Semen analysis is low volume and shows
decreased sperm density and low motility.
What is the next step in management?
a. Administer testosterone
b. Measure serum testosterone
c. Measure thyroid hormone
d. Repeat semen analysis
e. Refer for intrauterine insemination

4. STEPS IN THE WORK UP OF
INFERTILITY
STEP 1: Semen analysis
If normal, work up for anovulation.
STEP 2: Anovulation
If semen analysis is normal and
ovulation is confirmed, work up for
fallopian tube abnormalities.

STEP 3: Fallopian tube abnormalities

5. 1. SEMEN ANALYSIS
Diagnosis
Normal Values:
Volume >2 mL;
pH 7.2–7.8;
sperm density >20 million/mL;
sperm motility >50%; and
sperm morphology >50% normal
Management
If values abnormal, repeat semen analysis in
4–6 weeks.
Abnormal semen analysis: intracytoplasmic
sperm injection and IVF are fertility options.
No viable sperm: artificial insemination by
donor may be used.

6. 2. ANOVULATION
Diagnosis
Basal body temperature (BBT) chart: NO
midcycle temperature elevation
Progesterone: low
Endometrial biopsy: proliferative histology
(not routinely performed)
Management
Hypothyroidism or hyperprolactinemia are
causes of anovulation that can be treated.
Ovulation induction: clomiphene citrate
(agent of choice)/letrozole; if that fails, use
hMG;
ovarian hyperstimulation is the most
common side effect; monitor ovarian size
during induction.

7. 3. TUBE ABNORMALITIES:
HYSTEROSALPINGOGRAM AND
LAPAROSCOPY
Diagnosis
Chlamydia antibody: negative IgG
antibody test for chlamydia rules out
infection-induced tubal adhesions.
Management
Hysterosalpingogram (HSG): no further
testing if HSG shows normal anatomy
Laparoscopy: performed to visualize
the oviducts if HSG is abnormal;
if tubal damage is severe, IVF should
be planned

8. UNEXPLAINED INFERTILITY
The semen analysis is normal,
ovulation is confirmed, and
patent oviducts are noted.
No treatment is indicated.
About 60% of patients will go on
to achieve a spontaneous
pregnancy within the next 3
years.

9. A 35-year-old woman comes to the
gynecologist’s office complaining of
infertility for 1 year. There is no previous
history of pelvic inflammatory disease, and
she previously used oral contraceptive pills
for 6 years. Pelvic examination is normal.
Semen analysis is low volume and shows
decreased sperm density and low motility.
What is the next step in management?
a. Administer testosterone
b. Measure serum testosterone
c. Measure thyroid hormone
d. Repeat semen analysis
e. Refer for intrauterine insemination
ANSWER TO THE CASE STUDY

10. TREATMENT
Medical Measures
Surgical Measures
Induction of Ovulation
Artificial Insemination in
Azoospermia
Assisted Reproductive
Technology (ART)

11. MEDICAL MEASURES
Fertility may be restored by
treatment of endocrine
abnormalities, particularly
hypothyroidism or hyperthyroidism.
Women who are anovulatory
because of low body weight or
exercise may become ovulatory
when they gain weight or decrease
their exercise levels; conversely,
obese women who are anovulatory
may become ovulatory with loss of
even 5–10% of body weight.

12. SURGICAL MEASURES
Excision of ovarian tumors or ovarian foci
of endometriosis.
Microsurgical relief of tubal obstruction
due to salpingitis will reestablish fertility,
although with severe disease or proximal
obstruction, IVF is preferable.
In a male with a varicocele, sperm
characteristics may be improved
following surgical treatment. For men who
have obstructive azoospermia, trans-
epidermal sperm aspiration has been
successful.

13. INDUCTION OF OVULATION
Induction of ovulation may be
performed in combination with
intrauterine insemination (IUI), in which
washed ejaculated sperm are injected
directly into the upper uterine cavity
using a small catheter threaded through
the cervix, for patients with
oligoovulation/anovulation or
unexplained infertility.
1. Clomiphene citrate
2. Letrozole
3. Human menopausal gonadotropins
(hMG) or recombinant FSH

14. CLOMIPHENE CITRATE
Selective estrogen receptor modulator
Antagonist at estrogen receptors in
hypothalamus.
Prevents normal feedback inhibition
and increased release of LH and FSH
from pituitary, which stimulates
ovulation.
Used to treat infertility due to
anovulation (eg, PCOS).
May cause hot flashes, ovarian
enlargement, multiple simultaneous
pregnancies, visual disturbances.

15. AFTER A NORMAL MENSTRUAL PERIOD -
CLOMIPHENE 50 MG ORALLY SHOULD BE GIVEN DAILY FOR 5 DAYS,
TYPICALLY ON DAYS 3–7 OF THE CYCLE

16. LETROZOLE
Aromatase Inhibitor
Inhibit peripheral conversion of
androgens to estrogen.
Recent data suggest that letrozole is
more effective than clomiphene for
induction of ovulation in women with
PCOS.
There is a reduced risk of multiple
pregnancy, a lack of antiestrogenic
effects, and a reduced need for
ultrasound monitoring.

17. THE DOSE OF LETROZOLE IS 2.5–7.5 MG DAILY,
STARTING ON DAY 3 OF THE MENSTRUAL CYCLE

18. HUMAN MENOPAUSAL
GONADOTROPINS (HMG) OR
RECOMBINANT FSH—
hMG or recombinant FSH is indicated
in cases of hypogonadotropism and
most other types of anovulation
resistant to clomiphene treatment.

19. ARTIFICIAL INSEMINATION IN
AZOOSPERMIA
If azoospermia is present,
artificial insemination by a donor
usually results in pregnancy,
assuming female function is
normal. Using frozen sperm
provides the opportunity for
screening for sexually
transmitted infections, including
HIV infection.

20. ASSISTED REPRODUCTIVE
TECHNOLOGY (ART)
Couples who have not responded to
traditional infertility treatments and
those with occlusive tubal disease,
severe endometriosis, oligospermia,
and immunologic or unexplained
infertility, may benefit from ART.
All ART procedures involve ovarian
stimulation to produce multiple
oocytes, oocyte retrieval by
transvaginal sonography– guided
needle aspiration, and handling of
the oocytes outside the body.

21. WITH INVITRO FERTILIZATION
Eggs aspirated from the ovarian
follicles are fertilized with sperm in the
laboratory, resulting in the formation of
embryos.
Single embryo is transferred into the
uterine cavity with a cumulative
pregnancy rate of 55% after 4 IVF
cycles.

22. ANY
QUESTIONS?
THANK YOU