Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age,
with an incidence of 5 -10%. Classically clomiphene citrate (CC) is the first approach to
induce ovulation in patients with PCOS. Although 70-80% of PCOS women can ovulate by the
treatment with CC, only 40%of the PCOS women become pregnant. Women who do not ovulate with
increasing doses of CC are described as being CC-resistant and remain a major challenge in
gynecologic endocrinology. Traditional alternatives for CC-resistant patients include
gonadotropin therapy and laparoscopic ovarian diathermy.
Letrozole is an orally-active aromatase inhibitor, with good potential for ovulation
induction. Letrozole acts by reducing estrogen production by blocking androgens to estrogens
conversion. Additionally, it has no adverse effect on endometrium and cervical mucus (4).
This releases the pituitary from negative feedback of estrogens and releases FSH. Also, an
added positive effect is increased follicular sensitivity to FSH through amplification of FSH
receptor gene expression.
Laparoscopic ovarian drilling (LOD) can avoid or reduce the need for gonadotropins for
ovulation induction. Several potential mechanisms of action of LOD have also been suggested.
The reduction of inhibin production following LOD is followed by an increase in FSH secretion
and recruitment of a new cohort of follicles. Other theory is restoration of normal
production of the putative gonadotropin surge after laparoscopic ovarian electrocautery.
Moreover, drainage of androgens and inhibin from follicles surface may inhibit the excessive
collagenisation of overlying ovarian cortex and facilitate Softening of ovarian tunica.
Neighbouring follicles that are not undergoing atresia may then mature and gain access to the
ovarian surface, facilitating ovulation. Initiation of normal inhibin B pulsatility by LOD
appears to correlate with the postoperative onset of ovulatory cycles.
The main drawbacks of LOD are adhesions formation and ovarian atrophy. That is why minimising
the number of diathermy points and avoiding diathermy near the ovarian hilum are recommended.
All women with clomiphene resistant PCOS attending the subfertility clinic of Cairo
university hospitals will be invited to participate in the study. PCOS diagnosis will be
based on chronic anovulation and sonographic picture of polycystic ovaries. Clomiphene
resistance will be defined as failure of ovulation in spite of receiving 150mg of clomiphene
citrate for 5 days starting from the 3rd-5th day of the menstrual cycle.
Exclusion criteria are age >40 years, other causes of infertility, hyperprolactinaemia,
previous Letrozole or LOD therapy, and body mass index (BMI)>35.
The study will be explained to all the participants and a written informed consent will be
obtained before participation.
Full history will be taken followed by complete examination and sonographic evaluation.
Sonographic picture of polycystic ovaries will be defined when there are at least 12
follicles 2-9mm in the ovary and/or ovarian volume>10cm3 140 women with clomiphene resistant
PCOS will be randomly divided into 3 equal groups using computer generated random numbers.
Group 1 will receive Letrozole, group 2 will have LOD and group 3 will act as the control
group with no intervention.
Group 1 will receive Letrozole (Femara®, Novartis, Switzerland) 2.5mg twice daily for 5 days
starting from the 3rd day of menstruation or progesterone withdrawal bleeding. Group 2 will
have LOD in which the ovaries will be stabilised by grasping the ovarian ligament and
monopolar diathermy will be used to do 4-10 punctures in each ovary. The number of punctures
will be individualised according to the size of the ovary.
Serial vaginal ultrasound scans were done starting from the 10th day of menstruation, the
frequency of monitoring will be individualized according to the women's response. When the
dominant follicle reaches 17mm or more women will receive Human chorionic gonadotrophin
(Choriomon® IBSA, Switzerland) 5000IU and a timed intercourse will be advised 36 hours later.