Ovarian Laser Treatment in Women With Polycystic Ovarian Syndrome: A Randomized Study on the Laser Dose
Condition: Anovulation; Polycystic Ovary Syndrome; Infertility
MeSH terms: Polycystic Ovary Syndrome; Infertility; Anovulation; Syndrome
Study type: Observational

Summary: 
      BACKGROUND: A new effective way, transvaginal ultrasound-guided ovarian interstitial
      laser-coagulation treatment, in management of anovulation in patients with polycystic ovary
      syndrome (PCOS), has been presented in the data published. But, the optimal number of laser
      coagulation points in the ovarian interstitial to be applied at the procedure is unclear.
      This clinic trial aims to explore an optimal laser dose for this new protocol. METHODS:
      Fifty-six PCOS women with clomifene citrate-resistant underwent ultrasound-guided
      transvaginal ovarian interstitial YAG-laser treatment. By random list table，all subjects were
      randomly divided into four groups in terms of the number of laser coagulation points made in
      their ovaries as follows: group A, one coagulation point per ovary; group B, two points;
      group C, three points; group D, four to five points. The size of each point was about 10 mm
      in diameter on the ovarian plane monitored by transvaginal ultrasound. Postoperative
      ovulation rate, pregnancy rate and some biochemical parameters were compared among four
      groups.
    

Detailed description: 
      Materials and methods Subject selection Fifty-six patients with anovulatory infertility due
      to PCOS were included in the study between January 2005 and December 2007. All women
      presented with oligo-/amenorrhea and anovulation for at least 2 years and were seeking
      pregnancy. The mean (± SD) age was 29.1 ± 3.1 years and the mean duration of infertility 3.3
      ± 2.0 years. The mean body mass index (BMI) was 22.9 ± 3.5 kg/m2. All subjects had polycystic
      ovaries on transvaginal ultrasound scan (TVS) (Aloka-1000, UST-985, 5 MHz transvaginal probe,
      Aloka Co. Ltd, Tokyo, Japan), and the diagnosis of PCOS was made according to criteria of The
      Rotterdam (The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2003). Serum
      concentrations of FSH (5.4±2.3 IU/L), LH (11.8±3.2IU/L) and T (3.79±1.54nmol/L) were assessed
      at the third day of progesterone-induced bleeding (natural progesterone injection; Guangzhou
      Minxing pharmaceutical company, Guang-Zhou, China). TVS examination revealed bilateral
      ovarian enlargement and 10-30 subcapsular follicles of 2-8 mm in diameter in unilateral ovary
      with a stromal hypertrophy. All cases have received incremental clomifene citrate (CC) doses
      (50, 100, and 150mg), to which they failed to respond. A normal hysterosalpingography or
      laparoscopy had to have been recorded in the past three years prior to ovarian interstitial
      laser treatment. Any contraindications to surgery, previous treatment with LOD and the
      presence of tubal or male factors for infertility were considered as exclusion criteria. The
      study was approved by the Ethics Committee of Shen-Zhen Maternity and Child Healthcare
      Hospital and the Institutional Review Board of Shen-Zhen Bureau of Science and Technology of
      China. Subjects all signed an informed consent form.

      Protocol Study design This was a prospective, randomized study. Fifty-six subjects meeting
      the enrolled criteria were randomly divided into four groups of A、B、C、D according to a
      computer-generated random list. Randomization occurred after patients agreed to inclusion in
      the study (Figure 1). After randomization, women who were allocated in same group were
      intervened with same laser dosage during ovarian interstitial laser treatment. For each group
      of A、B、C、D, the number of laser coagulation points made in their ovaries as follows: group A,
      one coagulation point per ovary; group B, two points; group C, three points; group D, four to
      five points. To each point, the size of laser coagulation zone was 10 mm in diameter (a light
      spot of diameter 10 mm on the ovarian plane monitored by transvaginal ultrasound).

      Techniques of ovarian interstitial laser treatment The procedure of transvaginal
      ultrasound-guided ovarian interstitial laser treatment has been detailed in previous data
      (Zhu et al., 2006). All participants were treated on the third day after progesterone-induced
      menstruation period. An intramuscular injection of 50-100mg of Pethidine (Pethidine
      Hydrochloride Injection, Shenyang First Pharmaceutical, NEPG, Shen-Yang, China) was
      administered to each women about 30 minutes before starting the operation. After emptying
      their bladder, the women were placed in lithotomy. They were then prepared using an aseptic
      vulva and vaginal douche. TVS was performed and the widest ovarian plane was found. Usually,
      one to three intraovarian points can be predetermined in the widest ovarian plane, in other
      words, one to three laser coagulation points can be accomplished on the widest ovarian plane.
      If not, the next largest ovarian plane was chosen as the next option until three to five
      laser coagulation points have be made in unilateral ovary. For each treatment point, a fibre
      optic cable of 400 um in diameter was sent to intraovarian point by means of a 17-gauge,
      35-cm-long needle (K-OPS-1035-Cook IVF; Brisbane, Australia) and the electrical laser
      (XH-YAG-100 Laser; Wuhan Xinghua Photoelectricity Co. Ltd, Wu-Han, China) was activated
      persistently for two to five minutes with a power of 3-5 W and current of 8-10 A, until a
      10-mm light spot appeared on the ovarian plane. In group A, only one laser treatment point
      was made per ovary; and group B, two points; group C, three points; group D, four to five
      points. The women stayed in bed for two to three hours after the surgery, after which they
      were re-examined with TVS in order to rule out intra-abdominal haemorrhage prior to
      discharge.

      Postoperative Monitoring Serum hormone concentrations At the second, fourth and sixth month
      after the operation, a blood sample was taken on day three of menstrual cycle for measurement
      of serum levels of LH, FSH, testosterone, prolactin (PRL), estradiol (E2) and progesterone if
      the women had a regular ovulation and menstrual cycle. If not, the blood sample was taken on
      day three of progesterone-induced withdrawal bleeding. Another blood sample was taken on day
      21 of the same cycle in order to measure the serum concentration of progesterone when
      ovulation could not be diagnosed by TVS.

      Follicle development and ovulation Follicular growth and ovulation was monitored monthly by
      TVS at four to five days intervals after the operation. The scanning was repeated after two
      to three days when the leading follicle reached diameter of 12 mm. When the dominant
      follicles reached a diameter of 16 mm. LH surge was detected by urinalysis. Combined this
      result with TVS, ovulation and the timing of sexual intercourse could be confirmed. If the
      ovulation intervals during the six postoperative months were within a range of 21-35 days,
      the woman was documented as a responder having regular ovulation. If spontaneous ovulation
      and menstruation did not occur during six postoperative months, the woman was categorized as
      a nonresponder. The women whose status was between both would be categorized as having
      irregular ovulation.

      Pregnancy and miscarriage A urine pregnancy test was performed if spontaneous menstruation
      did not occur during 16-19 days following ovulation. The pregnancy rate was calculated based
      on the women who conceived. Miscarriage would be considered, if gestational sac without
      cardiac action or previous cardiac action stopped, although a urine pregnancy test was
      positive.

      Adverse effects Adverse effects, including intra-abdominal haemorrhage, infection, injuries
      of internal organs and failure of ovarian function, were recorded.

      Analysis of the data Women were divided into four groups according to the number of laser
      coagulation points made in their ovarian interstitial as follows: group A (n=14) treated with
      one laser coagulation point per ovary, group B (n=14) two points, group C (n=14) three
      points, group D (n=14) four to five points. The means ± SD of the baseline and postoperative
      second, fourth and sixth month values among the four groups were calculated for the serum LH,
      FSH, testosterone, PRL, progesterone, E2 levels. Analysis of variance was used for
      statistical analysis. The ovulation rate and pregnancy rate were calculated based on the
      cases of postoperative spontaneous ovulation and pregnancy. Contingency table analysis was
      used to compare success rates, with P<0.05 considered statistically significant.
    

Intervention name(s): ovarian interstitial laser treatment; ovarian interstitial laser treatment; ovarian interstitial laser treatment; ovarian interstitial laser treatment
Intervention type(s): Procedure; Procedure; Procedure; Procedure
Intervention description(s): Different dose of laser: group A, one point per ovary.; Different dose of laser: group B, two points per ovary.; Different dose of laser: group c, three points per ovary.; Different dose of laser: group D, four-five points per ovary.
Other intervention name(s): Different ovarian laser coagulation points; Different ovarian laser coagulation points; Different ovarian laser coagulation points; Different ovarian laser coagulation points
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Fifty-six patients with anovulatory infertility due to PCOS were included in the study
        between January 2005 and December 2007. All women presented with oligo-/amenorrhea and
        anovulation for at least 2 years and were seeking pregnancy. The mean (± SD) age was 29.1 ±
        3.1 years and the mean duration of infertility 3.3 ± 2.0 years. The mean body mass index
        (BMI) was 22.9 ± 3.5 kg/m2. All subjects had polycystic ovaries on transvaginal ultrasound
        scan (TVS) (Aloka-1000, UST-985, 5 MHz transvaginal probe, Aloka Co. Ltd, Tokyo, Japan),
        and the diagnosis of PCOS was made according to criteria of The Rotterdam (The Rotterdam
        ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2003).
      
Keywords: anovulation; laser; ovarian interstitial; polycystic ovary syndrome; ultrasound-guided