Letrozole Versus Clomiphene Citrate for Ovulation Induction in Women With Poly Cystic Ovary Syndrome ( PCOS )

The aim of this study is to compare the efficacy of letrozole on ovulation induction to that of clomiphene citrate in women suffering polycystic ovary syndrome.

Research question:

In women with PCOS , dose letrozole effective in ovulation induction as clomiphene citrate?

Researcher hypothesis:

In women with pcos , letrozole may be as effective as clomiphene citrate in ovulation induction.

Patients and methods Site: this study will be recruited from women attending infertility outpatient clinic at Ain Shams university maternity hospital.

Design: Randomized controlled trial.

Study population: 110 infertile women diagnosed as polycystic ovary syndrome (PCOS) at the age group of 20-35 distributed randomly:

• 55 women will receive letrozole 2.5mg twice daily orally from the 2nd day to the 6thday of the cycle for three successive cycles.
• 55 women will receive clomiphene citrate 50 mg twice daily orally from the 2nd day to the 6thday of the cycle for three successive cycles.

Inclusion criteria:

1. Age between 20-35
2. Primary or secondary infertility
3. Patients diagnosed as PCOS according to Rotterdam criteria :

Menstrual irregularities:

• oligomenorrhea and/or anovulation.
• Oligomenorrhea (menses that occur at intervals greater than 35 days)

• Excess androgen activity. - Clinically: hirsutism .

  • Biochemically: elevated serum androgen. polycystic ovaries (by gynecologic ultrasound)

Exclusion criteria:

Any patients have any causes of infertility other than which mentioned in the inclusion criteria as:

1. Hyperprolactinemia.

2. Male factor of infertility.

   WHO Guidelines 2010 for Normal seminal fluid analysis :

   • Volume> 1.5 ml
   • ph 7.2 to 8.0
   • Liquefaction time 20 to 30 min
   • Sperms concentration >15 million/ml
   • Total motility 40%(Progressive motility + non progressive motility)
   • Progressive motility 32%
   • Morphology > 4% normal forms
3. Thyroid dysfunction.
4. Diabetes Mellitus.
5. Known or suspicious tubal factor infertility ( by hysteroslapingograrhy (HSG) or laparoscope.
6. Endometrioses or pelvic inflammatory diseases .

Patients will be subjected to:

Complete history taking:

1. Details a bout name, age
2. Menstrual history with determination of menarche
3. Amenorrhea or oligomenorrhea , Regularity of the cycle
4. History of endocrine disease.

5. History of previous operations.

   Physical examination:

   General examination:

   With special concern to:

   --Acne.

   --Hirsutism .

   • Weight.
   • Height
   • BMI was determined :

   Wt. in kg ـــــــــــــــــــ =

   ) Height in m)2

   • Abdominal examination:

   for scar of previous pelvic or abdominal operations .

   • Pelvic examination:

   vaginal examination for enlarged cystic ovaries.

   • ultrasound for diagnosis of pcos.
   • The patients will randomly assigned to receive either letrozole (2.5 mg twice daily ) or clomiphene citrate (50 mg twice daily ) from day 2 to day 6 of menstrual cycle .
   • Follicular monitoring will be done by transvaginal ultrasonography (TVS) on alternate days from day 9 of menstrual cycle until a mature follicle detected. Follicle considered mature when it attained 18 mm in size or more by averaging inner two diameters of the follicle.
   • A single injection of 10,000 IU human chorionic gonadotrophin (hCG) will be given, if at least one follicle attained 18 mm. TVS will be done after 48 h of hCG injection to determine follicle rupture. If the follicle found unruptured, TVS repeated after 72 h of the hCG injection to detect whether follicle has ruptured or not. Ovulation ascertained by observing rupture of the follicle by ultrasonogram (USG).
   • Endometrial thickness of 8 mm considered a satisfactory response of the endometrium.
   • on day 21 serum progesterone level will measured. A progesterone level of 10 ng/ml considered as ovulatory.

   PARAMETERS

   Primary outcome measure :

(1) Rate of ovulation assessed by number of mature follicles produced per cycle .

Secondary outcome measures :

(2) Serum progesterone level on day 21 ( assessed up to 24 weeks). (3) Mean endometrial thickness ( assessed up to 24 weeks). (4) Chemical pregnancy ( assessed up to 24 weeks). (5) Ongoing pregnancy ( assessed up to 24 weeks).