Current Women’s Health Reviews, 2006, 2, 91-95 91 Transvaginal Hydrolaparoscopic Ovarian Drilling for Infertile Women with Polycystic Ovary Syndrome

Hiroaki Shibahara*, Yuki Hirano and Mitsuaki Suzuki

Department of Obstetrics and Gynecology, Jichi Medical School, Tochigi, Japan

Abstract: Polycystic ovary syndrome (PCOS) is a syndrome of ovarian dysfunction showing cardinal features of hyperandrogenism and polycystic ovarian morphology. It is one of the most common reproductive endocrine disorders in young adult women, showing clinical signs of menstrual disorder, anovulation, hirsutism, acne, and obesity. Frequently, this group of patients present with infertility due to chronic oligoovulation or anovulation. In cases that do not respond to medical induction of ovulation, ovarian surgery such as ovarian wedge resection via laparotomy or ovarian drilling by trans-abdominal laparoscopy has been utilized. Laparoscopic ovarian drilling (LOD) by the trans-abdominal approach has been widely used to induce ovulation in PCOS women after failure of treatment with clomiphene citrate. So far, many authors have reported high rates of ovulation (~ 80%) and pregnancy (~ 60%) following LOD. Recently, a transvaginal method for laparoscopy, named transvaginal hydrolaparoscopy (THL), was developed near the end of the 20th century. Since then, THL has been performed for diagnostic purposes in infertile women. More recently, THL has been performed for operative laparoscopy, especially for ovarian drilling in women with PCOS. This novel technique, transvaginal hydrolaparoscopic ovarian drilling (THLOD) using a laser or bipolar electrosurgery, appears to be an effective minimally invasive procedure to induce ovulation in women with PCOS. Larger studies to assess the safety and long-term efficacy of THLOD are needed. This review article describes the minimally invasive operation for infertile women with PCOS by THLOD. Keywords: Polycystic ovary syndrome, anovulation, transvaginal hydrolaparoscopic ovarian drilling, ovarian wedge resection, laparoscopic ovarian drilling.

INTRODUCTION In recent years, however, because of the rapidly expanding use of techniques involving laparoscopy, surgical Polycystic ovary syndrome (PCOS) is a syndrome of treatment has received renewed interest. Laparoscopic ovarian dysfunction showing cardinal features of ovarian drilling (LOD) by the trans-abdominal approach has hyperandrogenism and polycystic ovarian morphology [1]. It been widely used to induce ovulation in women with PCOS is one of the most common reproductive endocrine disorders after failure of treatment with clomiphene citrate [4]. So far, in young adult women, showing clinical signs of menstrual it has been shown that LOD is effective for inducing disorder, anovulation, hirsutism, acne, and obesity. ovulation, and the pregnancy rate following LOD seems to Frequently, this group of patients present with infertility due be acceptable. to chronic oligoovulation or anovulation. Approximately 15 % of patients with PCOS remain anovulatory despite Near the end of the 20th century, a transvaginal method treatment with clomiphen citrate, and half of patients with for laparoscopy, named transvaginal hydrolaparoscopy PCOS who become ovulatory on this treatment fail to (THL), was developed and it was initially performed as a conceive [2]. The alternative of gonadotropin stimulation or diagnostic laparoscopy in infertile women [5]. Afterwards, surgical treatment is often the next step for the treatment of THL was offered for the operative laparoscopy, especially in clomiphene citrate-resistant infertile women with PCOS. women with PCOS for ovarian drilling [6]. This novel technique, transvaginal hydrolaparoscopic ovarian drilling Since Stein and Leventhal reported that all women (THLOD) using a laser or bipolar electrosurgery, appears to menstruated regularly post ovarian wedge resection and be an effective minimally invasive procedure to induce some of them conceived [3], ovarian surgery has been used ovulation in women with PCOS [7-9]. It was suggested that to induce ovulation following unsuccessful medical THLOD has the same effectiveness as trans-abdominal induction of ovulation. Ovarian surgery has also been LOD. indicated in women who hyper-respond to gonadotropin therapy in order to avoid such complications as ovarian OVARIAN WEDGE RESECTION hyperstimulation syndrome (OHSS) or multiple gestations. In 1935, Stein and Leventhal found that some women with secondary amenorrhea displayed bilateral polycystic *Address corresponding to this author at the Department of Obstetrics and ovaries when laparotomy was performed to collect bilateral Gynecology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi- ovarian samples by wedge biopsies [3]. A series of seven machi, Kawachi-gun, Tochigi 329-0498, Japan; Tel: +81-285-58-7376; Fax: women underwent bilateral ovarian wedge resection thereby +81-285-44-8505; E-mail: [email protected] removing approximately 50 to 75 % of each ovary. All

1573-4048/06 $50.00+.00 © 2006 Bentham Science Publishers Ltd. 92 Current Women’s Health Reviews, 2006, Vol. 2, No. 1 Shibahara et al. women were still menstruating regularly at the time of of punctures to ameliorate the hyperandrogenic status in follow-up. After the surgery, pregnancies were achieved in PCOS women, previous studies have described a various infertile women [3]. These authors were the first to number of punctures carried out in each ovary, ranging from demonstrate the association of the unique polycystic ovarian 4 to 40 [14-16,19-22]. Recently, Amer et al. [23] showed by morphology with the key symptoms such as anovulation and a retrospective study that three punctures per ovary seemed abnormal uterine bleeding. to represent the plateau dose compared with two punctures Although the effectiveness of bilateral ovarian wedge per ovary. Malkawi et al. [24] also reported 5 punctures per resection for patients with PCOS has been well established, ovary were sufficient to improve the clinical and possible complications have been recognized. Removal of reproductive outcome compared with > 10 punctures per ovary. too much ovarian tissue may be the cause of ovarian dysfunction. Any operation on the ovary tends to produce As shown before, the vast majority of patients were adhesions that may involve the tubes. Toaff et al. [10] found to have adhesive disease following bilateral wedge reported that all of seven patients afflicted with continuing resection, while postoperative adhesions are less common infertility after bilateral ovarian wedge resection were found after laparoscopy than after laparotomy [25]. This was also to display peri-tubal adhesions. Three of them displayed confirmed in a rabbit model [26]. ovarian atrophy. Buttram and Vaquero [11] also reported Recently, the use of an insulated needle cautery [27] or that all patients were found to have adhesive disease within that of a harmonic scalpel [28] was shown to be associated one year of bilateral wedge resection in a series of 59 PCOS with a minimal complications including adhesion formation. patients. Therefore, ovarian wedge resection was largely In the former report, 11 (73.3 %) of 15 women performed abandoned because of the risks. It was replaced by medical LOD with insulated needle cautery were found to be free of ovulation induction with clomiphene and gonadotropins. adhesions by a second-look laparoscopy. However, Donesky and Adashi reported an overall The effectiveness and safety of LOD for ovulation aggregate pregnancy rate of 58.8 %, calculated after classical induction in infertile women with clomiphene citrate- bilateral ovarian wedge resection in 1,766 patients, in a resistant PCOS were systematically reviewed by Cochrane review collected from papers including uncontrolled series Database [29]. The author concluded that there is insufficient [12]. An interesting report by Stein noted regular menses evidence of a difference in cumulative ongoing pregnancy lasting more than 31 years in a patient after bilateral ovarian rates between LOD after 6-12 months of follow-up and 3-6 wedge resection [13]. However, the mechanism of action of cycles of ovulation induction with gonadotropins as a ovarian wedge resection is not fully understood. Therefore, it primary treatment. However, the rate of multiple pregnancies is unclear why some women with PCOS do not respond to was considerably reduced in those women who conceived the operation. Some possible mechanisms for the effects of following LOD. These findings suggest that LOD could be bilateral ovarian wedge resection or ovarian drilling have selected for women with clomiphene citrate-resistant PCOS been proposed, but they remain to be proven. For examples, who do not desire multiple pregnancies. a reduction in the levels of LH might lead to a decrease in stromal androgen production along with increasing FSH Donesky and Adashi [12] summarized the findings about levels, allowing follicular development to proceed to conception after LOD. A total of 729 patients were available ovulation [14]. Another mechanism is that inhibin levels are for the study from 27 references. Among them, 614 (82.4%) reduced after ovarian surgery, resulting in a secondary rise of ovulated either spontaneously or with the addition of FSH accompanied by reduced intrafollicular androgen levels medications (predominantly clomiphen citrate) to which they with subsequent appropriate follicular growth [15]. had not responded preoperatively. Four hundred and six of Furthermore, a 40% increase in the sex-hormone-binding 614 ovulatory patients conceived, giving a pregnancy rate of globulin (SHBG) concentrations has been reported after 66.1 % per ovulatory woman, which is similar to that ovarian surgery, which was associated with a significant obtained by medical induction of ovulation. reduction in the levels of androgens [16]. TRANSVAGINAL HYDROLAPAROSCOPIC LAPAROSCOPIC OVARIAN DRILLING OVARIAN DRILLING Patients with PCOS treated with gonadotropins often In 1998, THL was introduced as the first line procedure have a multi-follicular response and are exposed to the risks in the exploration of the adnexal structures in infertile of OHSS and multiple pregnancies. In the early 1980’s, women [5]. Because of the advantages of THL, including laparoscopic ovarian electrocautery and ovarian laser accurate inspection of adnexal structures without vaporization was employed as alternative surgical treatments manipulation, it became clear that THL is a less traumatic to ovarian wedge resection in the management of PCOS and more suitable outpatient procedure than diagnostic failing to respond to medical induction of ovulation [17]. laparoscopy [30,31]. The risks of a general anesthetic are Laparoscopic procedures to induce ovulation have been avoided, and there is less chance of trauma to major vessels. recognized as more useful because of their lower Therefore, we have been performing THL for a diagnostic invasiveness compared to wedge resection. To date, several laparoscopy on infertile women based on any of the techniques of laparoscopic surgery have been described, following four indications: i) tubal obstruction and/or including ovarian biopsy [4], electrocautery [17], and laser peritubal adhesion is suggested by hysterosalpingography, ii) technology [18]. Most have involved formation of multiple serum antibody against C. trachomatis is positive [32,33], iii) holes on the surface of the ovary using a laser, and this diagnosis of early-stage endometriosis, and iv) unexplained procedure is known as LOD. Concerning the optimal number infertility [30,31]. Our group also reported the application Transvaginal Hydrolaparoscopic Ovarian Drilling for Infertile Women Current Women’s Health Reviews, 2006, Vol. 2, No. 1 93 and usefulness of THL for transvaginal salpingoscopy of Douglas (Fig. 1b, 1c). A 5.5-mm blunt trocar is inserted [34,35]. by a stab incision in the posterior fornix. Then a 2.7-mm THL was originated from culdoscopy, which fell into diameter semirigid endoscope is used with an optical angle disfavor in the 1970s when laparoscopy was developed and of 30° and a flow channel attached to a 3-CCD digital videocamera (Fig. 1d). The saline irrigation is continued widely diffused. In 1972, Paldi et al. [36] reported that they performed ovarian wedge resection after ovarian extraction throughout the procedure to keep the bowel and tubo-ovarian in the fornix assisted by culdoscopy in 25 women. However, structures afloat. The posterior region of the uterus and the they did not provide pregnancy rates following the operation. bilateral tubo-ovarian structures are carefully observed, and tubal passage is confirmed using indigo carmine. Tubo- Although THL was initially developed as a method for ovarian structures and tubal passages are carefully diagnostic laparoscopy, Fernandez et al. [6,8] have recently investigated using THL (Circon ACMI, Stamford, CT, reported the feasibility of ovarian drilling by THL for PCOS. USA). They reported the usefulness of THL for the treatment of Then, ovarian drilling is performed using an Nd:YAG PCOS by ovarian drilling. They performed ovarian drilling using bipolar electrosurgery by THL in 80 clomiphen citrate- laser (STAGE MY-100, LASER PERIPHERALS LLC, MN, resistant anovulatory women with PCOS. During a mean USA) or Holmium laser (VersaPulse, Boston Scientific, MA, follow-up of 18.1 months, 73 (91 %) patients recovered USA) to ablate portions of the ovarian cortex (Fig. 1e, 1f). A regular ovulatory cycles. The cumulative pregnancy rate was sterile quartz glass fiber measuring 1 mm in core diameter is passed through the operating channel of the laparoscope 60 % for spontaneous and stimulated cycles, with 40% using a special laser fiber steering device with a deflectable imputed to drilling alone [8]. It was also reported that there tip (Fig. , ). The power used ranges up to 10 W. The were no complications. 2b 2c focused laser beam is used at a distance of 1.5 mm to 3.0 Our group has also been performing THLOD using a mm to create approximately 40 holes on the surface of each laser [7]. The advantages and disadvantages of THLOD and ovary (Fig. 2d, 2e, 2f). gonadotropin treatments are summarized in Table 1. THLOD So far, 7 infertile women with PCOS, including 5 women has 3 advantages. Ovulation and pregnancy rates are the with clomiphene citrate-resistant PCOS and 2 women with same as those for gonadotropin treatments. OHSS and the risk of developing OHSS, have undergone THLOD. multiple pregnancies are reduced. Furthermore, if ovulation Except for one patient who dropped out of the study, 6 is achieved, the frequency of visiting the outpatient clinic for patients resumed having regular ovulatory cycles without monitoring the follicular status can be reduced. However, THLOD might have some disadvantages, including the risks developing OHSS. In 4 (67%) of 6 patients, pregnancies were established; one by timed intercourse during the of anesthetic and operative complications or possible spontaneous cycle, two by intra-uterine insemination recurrence of oligoovulatory cycles. following clomiphene-FSH-HCG treatment, and one by IVF- The procedure for THLOD is illustrated in Fig. 1. It is ET. The pregnancy courses in these patients have been performed as we previously described [7]. In brief, THLOD uneventful to this point. There were no intra- or is performed under general anesthesia in the lithotomy postoperative complications of THLOD [9]. position. After disinfections, a Hys-cath (Sumitomo Bakelite Co. Ltd., Tokyo, Japan) is inserted into the uterine cavity for SUMMARY chromotubation. The uterine cervix is lifted with a Ovarian surgery for the treatment of PCOS has been tenaculum placed on the posterior lip. A Veress needle is shown to be useful in anovulatory infertile women who do introduced 1.5 cm below the cervix and inserted into the not respond to medical induction of ovulation. LOD by the pelvic cavity Fig. 1a. Approximately 100 ml of normal trans-abdominal approach has been used to induce ovulation saline solution is instilled through the cannula in the pouch in women with PCOS after failure of treatment with

Table 1. Comparison of the Advantages and Disadvantages by the Treatments for PCOS Women

Treatment Advantages Disadvantages

THLOD* 1. Ovulation and pregnancy rates are same as the treatment by 1. At the risks of complications by anesthesia and surgical gonadotropins. operation. 2. OHSS and multiple pregnancy are reduced. 2. Possible recurrence of oligo-ovulatory cycles. 3. If achieved ovulation cycle, it could be reduced the frequency of visiting to the out patient clinic for monitoring the follicular status.

Gn** 1. Ovulation and pregnancy rates are same as the treatment by 1. Higher incidence of OHSS and multiple pregnancy. laparoscopic ovarian drilling. 2. Higher frequency of visiting to the out patient clinic. 2. No surgical complications.

* : transvaginal hydrolaparoscopic ovarian drilling **: gonadotropin 94 Current Women’s Health Reviews, 2006, Vol. 2, No. 1 Shibahara et al.

Fig. (1). Procedure for transvaginal hydrolaparoscopic ovarian drilling using a laser. The procedure for transvaginal hydrolaparoscopic ovarian drilling (THLOD) using a laser is described. a) A Veress needle is inserted into the pelvic cavity. b, c) Normal saline solution is instilled through the cannula in the pouch of Douglas. d) A blunt trocar is inserted by a stab incision in the posterior fornix. Then a semirigid endoscope is used with an optical angle of 30° and a flow channel attached to a 3-CCD digital videocamera. Tubal passage is confirmed using indigo carmine. e, f) THLOD is performed using a laser to ablate portions of the ovarian cortex.

Fig. (2). Performance of transvaginal hydrolaparoscopic ovarian drilling using a laser. a) A polycystic ovary behind the uterus is visible through THL. b) Introduction of the laser probe through the auxiliary channel of the sheath. The focused laser beam was used from a distance of 1.5 mm to 3.0 mm. c-e) Approximately 40 holes were made on the ovarian cortex. f) Final phase of ovarian drilling. Transvaginal Hydrolaparoscopic Ovarian Drilling for Infertile Women Current Women’s Health Reviews, 2006, Vol. 2, No. 1 95 clomiphene citrate. Following the introduction of THL as the [19] Greenblatt E, Casper RF. Adhesion formation after laparoscopic first line procedure for the diagnostic laparoscopy, THLOD ovarian cautery for polycystic ovarian syndrome. Lack of correlation with pregnancy rate. Fertil Steril 1993; 60: 766-770. was developed as an alternative minimally invasive surgery [20] Li TC, Saravelos H, Chow M, Chisabingo R, Cooke ID. Factors for PCOS patients. 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Received: June 28, 2005 Revised: July 11, 2005 Accepted: July 25, 2005