FSH/LH Ratio as a Predictor of IVF Outcome in Young and Older Women
Condition: Invitro Fertilization
Study type: Interventional
Phase: Phase 4

Summary: 
      All women had normal uterine cavity determined by previous hysterosalpingography or
      hysteroscopy. Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and
      women with abnormal endocrine functions as abnormal thyroid or adrenal functions were
      excluded. Any woman with ovarian cyst or azopermic male partner was also excluded.

      The patients were subjected to history taking, including age, duration, type and cause of
      infertility and medical history. Full examination including general and abdominal and vaginal
      examination was done followed by ultrasound evaluation for presence of 3 or more pre-antral
      follicles and exclusion of ovarian cysts.

      Basal day 3 hormonal evaluation for FSH, LH and E2 in a natural cycle was done. E2, FSH and
      LH levels were determined using Immulite system (Siemens Healthcare diagnostics,UK).The
      intra- and inter-assay coefficients of variation were 15% and 16% for E2, 4.8% and 26% for
      LH. FSH analytical sensitivity was 0.1 mIU/ml.

      All participants underwent long protocol. Daily SC injection of Triptorelin : Decapeptyl 0.1
      mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle
      and continued till the day of hCG injection. Gn stimulation started after fulfilling
      stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l [18]
      with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a
      starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response.
      then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound
      evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on
      alternate days according to the ovarian response to treatment starting on treatment cycle day
      (6) for folliculometry and endometrial thickness and pattern.

      Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when at least 2 follicles
      reached a mean diameter of 18 mm [18]

      Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no
      adequate follicular growth (<3 mature follicles).

      Ovum pick-up (OPU) was done 34-36 hours after hCG injection under transvaginal ultrasound
      guide.
    

Detailed description: 
      All women had normal uterine cavity determined by previous hysterosalpingography or
      hysteroscopy. Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and
      women with abnormal endocrine functions as abnormal thyroid or adrenal functions were
      excluded. Any woman with ovarian cyst or azopermic male partner was also excluded.

      The patients were subjected to history taking, including age, duration, type and cause of
      infertility and medical history. Full examination including general and abdominal and vaginal
      examination was done followed by ultrasound evaluation for presence of 3 or more pre-antral
      follicles and exclusion of ovarian cysts.

      Basal day 3 hormonal evaluation for FSH, LH and E2 in a natural cycle was done. E2, FSH and
      LH levels were determined using Immulite system (Siemens Healthcare diagnostics,UK).The
      intra- and inter-assay coefficients of variation were 15% and 16% for E2, 4.8% and 26% for
      LH. FSH analytical sensitivity was 0.1 mIU/ml.

      All participants underwent long protocol. Daily SC injection of Triptorelin : Decapeptyl 0.1
      mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle
      and continued till the day of hCG injection. Gn stimulation started after fulfilling
      stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l [18]
      with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a
      starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response.
      then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound
      evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on
      alternate days according to the ovarian response to treatment starting on treatment cycle day
      (6) for folliculometry and endometrial thickness and pattern.

      Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when at least 2 follicles
      reached a mean diameter of 18 mm [18]

      Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no
      adequate follicular growth (<3 mature follicles).

      Ovum pick-up (OPU) was done 34-36 hours after hCG injection under transvaginal ultrasound
      guide.

      Metaphase II ocytes were analyzed. ICSI procedure was performed in all cases. Fertilization
      was assessed 16-18 h after ICSI and embryo quality was evaluated 2 and 3 days after ICSI was
      determined according to the number of blastomeres and the degree of fragmentation and
      multinucleation[19]. Oocytes were collected and embryos were cultured in ISM1culture medium
      (Origio medicult media, Denmark).

      Transfer of cleaving embryos was done on day 3 after oocyte retrieval (using Labotect
      semi-rigid catheter; labotect GmbH, Germany) All patients received luteal support in the form
      of daily progesterone (Prontogest, Amsa, Italy) 100 mg IM daily starting from day of ovum
      retrieval [18] till day of hCG testing. Serum β hCG level was assessed on day 14 after ET .

      The primary outcome parameters evaluated were clinical pregnancy (defined as the presence of
      gestational sac containing fetal hearts on ultrasound scan). Other parameters included
      occurrence of multiple pregnancy, Abortion and ectopic cases per pregnancies, dose of Gn,
      duration of stimulation, E2 and Progesterone levels at day of HCG triggering, endometrial
      thickness at day of HCG triggering, number of follicles > 16 mm , number of retrieved
      follicles , number of oocytes fertilized, number of good ET and cancellation rate.

      The participants were divided according to age into 2 groups: Group 1<35 years old who are
      further subdivided according to FSH/LH ratio into G1A with FSH/LH ratio <2 and G1B with
      FSH/LH ratio ≥2. Group 2 ≥ 35 years old who are further subdivided according o FSH/LH ratio
      into G2A with FSH/LH ratio <2 and G2B with FSH/LH ratio ≥2. The use of cutoff value is
      supported by previous studies [20,21]
    

Intervention name(s): Invitro fertilization
Intervention type(s): Procedure
Intervention description(s): All participants underwent long protocol. Daily SC injection of Triptorelin 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG injection. Gn stimulation started in a starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response. then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days
Triggering by HCG 10000 IU IM when at least 2 follicles reached a mean diameter of 18 mm [18]
Ovum pick-up (OPU) was done 34-36 hours after hCG injection Transfer of cleaving embryos was done on day 3 after oocyte retrieval
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Diagnostic