Laparoscopic Ovarian Drilling and Subendometrial Blood Flow
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Syndrome
Study type: Interventional

Summary: 
      Serum level of total testosterone was measured in the early follicular phase (days 2-4 of
      spontaneous cycle in oligomenorrhic patients). To start the study in amenorrhic patients
      (after exclusion of pregnancy) they received progesterone (oral Norethisterone Acetate 10 mg
      daily for 5 days) to induce withdrawal bleeding and total testosterone was measured in days
      2-4 of this withdrawal bleeding.

      Color Doppler ultrasound scanning will be performed to assess the subendometrial blood flow.
      The subendometrial region was observed and analyzed in each woman using color and power
      Doppler flow ultrasonography. By means of color and power Doppler flow imaging, color signals
      was searched for in the subendometrial region and areas of maximum color intensity,
      representing the greatest Doppler frequency shifts, was visualized, then selected for pulsed
      Doppler examination. Pulsatility index (PI) and resistance index (RI) were calculated in each
      selected Doppler wave.

      Laparoscopic ovarian drilling was performed under general anesthesia with good muscle
      relaxation and endotracheal intubation using the three-punctures technique (one puncture 10mm
      at the umbilicus and the other two punctures 5mm at both iliac fossa) in the early follicular
      phase (after stoppage of menstrual or withdrawal bleeding).

      A specially designed monopolar electrocautery probe was used to penetrate the ovarian capsule
      at 4 points (regardless of the size of the ovary), with the aid of a short burst of monopolar
      diathermy. The probe (which has a distal stainless steel needle measuring 10 mm in length and
      2 mm in diameter) was applied to the surface of the ovary at a right angle to avoid slippage
      and to minimize surface damage. A monopolar coagulating current at a 40 W power setting was
      used. The needle was pushed through the ovarian capsule for about 4 mm depth into the ovarian
      tissue and electricity was activated for 4 seconds. The ovary was then cooled using 200 ml
      crystalloid solution before releasing the ligament.

      Follow up:

      Total testosterone and blood flow assessment (PI - RI) of the subendometrial region were
      performed again in the early follicular phase (days 2-4 of the menstrual cycle) of the first
      post-operative spontaneous menstruation (which occurred within 10 weeks after the operation).

      Also, patients were followed to detect ovulation. ovulating patients were followed for 6
      months to detect pregnancy.
    

Detailed description: 
      Effect of Laparoscopic Ovarian Drilling on Subendometrial Blood Flow in Women with Polycystic
      Ovary Syndrome

      Patients and methods:

      This interventional study was carried out in the Department of Obstetrics and Gynecology
      (Infertility, Ultrasound and Gynecologic endoscopy units), Faculty of Medicine, Zagazig
      University Hospitals in the period between July 2016 and October 2017. The study included 200
      infertile women (primary or secondary infertility) with PCOS attended the infertility
      outpatient clinic and fulfilled the following inclusion criteria: 1- Patients' ages 20 to 34
      years; 2- BMI 18-25 kg/m2; 3- PCOS was diagnosed according to Rotterdam criteria, 2003 (two
      criteria are sufficient for diagnosis of PCOS): (i) oligo-and/or an-ovulation; which is
      manifested clinically by amenorrhoea or oligomenorrhoea, (ii) hyperandrogenism (clinical
      and/or biochemical); (hirsutism and/or elevated serum level of total testosterone), (iii)
      polycystic ovaries by ultrasound (each ovary contains 12 or more follicles measuring 2-9 mm
      and/ or ovarian volume more than 10 ml), ( we included only patients who had the three
      criteria of PCOS) , and previously documented anovulation by transvaginal ultrasound
      follicular monitoring while taking incremental doses of clomiphene citrate (clomiphene
      citrate resistant); 4- Hysterosalpingography and husband semen analysis were normal in all
      subjects. 5- All women in the study were free of any medical illness and had not received any
      medications in the last 6-9 months before the study apart from clomiphene citrate.

      Exclusion criteria were: 1- Other PCOS like syndromes (late onset congenital adrenal
      hyperplasia-androgen producing tumors-Cushing,s syndrome), hyperprolactinemia and thyroid
      abnormalities; 2- Gross ovarian pathology either diagnosed preoperatively by ultrasound or
      intraoperatively by laparoscopy; 3- Any uterine pathology diagnosed preoperatively by
      ultrasound, HSG or hysteroscopy; or intraoperatively by endoscopy and suspected to cause
      infertility; 3- Other causes of infertility even if diagnosed during laparoscopy such as
      tubal pathology and pelvic endometriosis or adhesions; 4- Previous uterine, tubal or ovarian
      surgery. 5- Contraindications to laparoscopy and general anesthesia; 6- Pregnancy before the
      first post-operative menstrual cycle.

      After full detailed history taking, general, abdominal and local examination and exclusion of
      any associated medical disorders, transabdominal and/or transvaginal ultrasound was done to
      exclude patients with ovarian or pelvi-abdominal masses. Other investigations were done to
      fulfill the inclusion and exclusion criteria (serum prolactin level, free T3, free T4, TSH).
      Serum level of total testosterone was measured in the early follicular phase (days 2-4 of
      spontaneous cycle in oligomenorrhic patients). To start the study in amenorrhic patients
      (after exclusion of pregnancy) they received progesterone (oral Norethisterone Acetate 10 mg
      daily for 5 days) to induce withdrawal bleeding and total testosterone was measured in days
      2-4 of this withdrawal bleeding. Total testosterone was done for all patients in the
      Laboratory of Zagazig University Hospitals by Electrochemiluminescence (ECL) technology
      (Cobas e 411 analyzer-Roche Diagnostics GmbH-D-68298 Mannheim-Germany).

      Transvaginal 2D color Doppler probe of Voluson 730 pro V machine (GE healthcare, Austria with
      a 3.5 MHz sector transducer for TAS and 7.5 MHz sector transducer for TVS) was used. While
      the patients in lithotomy position after evacuation of their urinary bladder and on the same
      days of total testosterone level assay, baseline 2D TVS was used to examine the uterus for
      any abnormality and measuring the uterine size and endometrial thickness and then to identify
      PCO criteria in both ovaries and ovarian volume was measured using ellipisoid prolate
      formulae (length X width X height X 0.523, which is calculated automatically by the software
      of the ultrasound machine), (each ovary contains 12 or more follicles measuring 2-9 mm and/
      or ovarian volume more than 10 ml) then color Doppler ultrasound scanning will be performed
      to assess the subendometrial blood flow. The subendometrial region was observed and analyzed
      in each woman using color and power Doppler flow ultrasonography. By means of color and power
      Doppler flow imaging, color signals was searched for in the subendometrial region and areas
      of maximum color intensity, representing the greatest Doppler frequency shifts, was
      visualized, then selected for pulsed Doppler examination. Pulsatility index (PI) and
      resistance index (RI) were calculated in each selected Doppler wave.

      Laparoscopic ovarian drilling was performed under general anesthesia with good muscle
      relaxation and endotracheal intubation using the three-punctures technique (one puncture 10mm
      at the umbilicus and the other two punctures 5mm at both iliac fossa) in the early follicular
      phase (after stoppage of menstrual or withdrawal bleeding). The zero-degree telescope (Karl
      Storz, Tuttlingen, Germany) was introduced to visualize the peritoneal cavity. The pelvis was
      thoroughly inspected for any pathology and the ovaries were examined for the features of
      polycystic ovary (bilateral ovarian enlargement with smooth glistening surface unbroken by
      the usual wrinkles and thick, smooth, whitish capsule). Methylene blue test was done for all
      patients to examine the tubal patency and bilateral tubal patency is mandatory before ovarian
      drilling.

      A specially designed monopolar electrocautery probe was used to penetrate the ovarian capsule
      at 4 points (regardless of the size of the ovary), with the aid of a short burst of monopolar
      diathermy. The probe (which has a distal stainless steel needle measuring 10 mm in length and
      2 mm in diameter) was applied to the surface of the ovary at a right angle to avoid slippage
      and to minimize surface damage. A monopolar coagulating current at a 40 W power setting was
      used. The needle was pushed through the ovarian capsule for about 4 mm depth into the ovarian
      tissue and electricity was activated for 4 seconds. The ovary was then cooled using 200 ml
      crystalloid solution before releasing the ligament.

      Follow up:

      Total testosterone and blood flow assessment (PI - RI) of the subendometrial region were
      performed again in the early follicular phase (days 2-4 of the menstrual cycle) of the first
      post-operative spontaneous menstruation (which occurred within 10 weeks after the operation).
      In non-menstruating patients, total testosterone and the blood flow assessment were performed
      by the end of the 10 weeks. In menstruating patients, this cycle was monitored to detect
      ovulation. Ovulation was assessed by serial transvaginal ultrasound until visualization of
      pre-ovulatory follicle of at least 18 mm. Ovulation was confirmed by seeing follicle collapse
      on subsequent transvaginal ultrasound, appearance of fluid in the Cul-de-sac and elevated
      mid-luteal serum progesterone level >5 ng/ml. Ovulating group was informed to report the
      occurrence of natural conception for 6 months after LOD. Pregnancy was diagnosed by positive
      pregnancy test with seeing intrauterine gestational sac by transvaginal ultrasound.

      Patients who did not menstruate (pregnancy was excluded at first) or did not ovulate within
      10 weeks after drilling as evidenced by poor or no follicular growth by serial transvaginal
      ultrasound folliculometry, and low mid-luteal serum progesterone level < 5 ng/ml were
      referred to another group of researchers for re-evaluation
    

Intervention name(s): Laparoscopic ovarian drilling
Intervention type(s): Procedure
Intervention description(s): A specially designed monopolar electrocautery probe was used to penetrate the ovarian capsule at 4 points, with the aid of a short burst of monopolar diathermy. The probe (which has a distal stainless steel needle measuring 10 mm in length and 2 mm in diameter) was applied to the surface of the ovary at a right angle to avoid slippage and to minimize surface damage. A monopolar coagulating current at a 40 W power setting was used. The needle was pushed through the ovarian capsule for about 4 mm depth into the ovarian tissue and electricity was activated for 4 seconds.
Intervention model: Single Group Assignment
Intervention model description: Laparoscopic ovarian drilling was performed under general anesthesia with good muscle relaxation and endotracheal intubation using the three-punctures technique (one puncture 10mm at the umbilicus and the other two punctures 5mm at both iliac fossa) in the early follicular phase. A specially designed monopolar electrocautery probe was used to penetrate the ovarian capsule at 4 points (regardless of the size of the ovary), with the aid of a short burst of monopolar diathermy. The probe (which has a distal stainless steel needle measuring 10 mm in length and 2 mm in diameter) was applied to the surface of the ovary at a right angle to avoid slippage and to minimize surface damage. A monopolar coagulating current at a 40 W power setting was used. The needle was pushed through the ovarian capsule for about 4 mm depth into the ovarian tissue and electricity was activated for 4 seconds. The ovary was then cooled using 200 ml crystalloid solution before releasing the ligament.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Polycystic Ovary Syndrome; Laparoscopic ovarian drilling; subendometrial blood flow