Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting 6-10% of women of reproductive age globally. It is characterized by menstrual irregularity, anovulation, hyperandrogenism, and polycystic ovaries. PCOS significantly impacts fertility and overall quality of life, making effective treatment strategies essential. Clomiphene citrate is often the first-line pharmacological treatment to induce ovulation in PCOS patients. However, approximately 20-30% of patients exhibit resistance to clomiphene therapy, necessitating alternative treatment options. Among these, laparoscopic ovarian drilling (LOD) has emerged as an effective surgical option.
What is Ovarian Drilling?
Ovarian drilling, also known as multiperforation or laparoscopic ovarian diathermy, is a surgical technique that involves puncturing the membranes surrounding the ovary using a laser beam or a surgical needle. This minimally invasive laparoscopic procedure differs from ovarian wedge resection, which involves cutting tissue. The contemporary version of ovarian wedge resection, laparoscopic ovarian drilling (LOD), is considered effective for gonadotropins in terms of live birth rates, but without the risks of iatrogenic complications in gonadotropin therapy.
The procedure is typically performed under general anesthesia. A small incision is made in the belly at the belly button, through which a tube is placed to inflate the belly with a small amount of air. This allows the surgeon to insert the viewing tool (laparoscope) without damaging internal organs. The surgeon looks through the laparoscope at the internal organs, and tools are inserted through other tiny incisions in the lower belly to make small holes in the ovaries.
How Does Ovarian Drilling Work?
The exact mechanism by which small perforations using heat or a laser result in follicular growth and ovulation is not fully understood. It's unknown whether the prevalent action is exerted through a direct effect on the ovary or through a systemic endocrine mechanism. The most plausible mechanism is that the thermal destruction of ovarian follicles and a part of the ovarian androgen-producing stroma results in the reduction in local and serum androgens, re-establishing an intrafollicular environment more convenient for normal follicular maturation and ovulation and a secondary rise in follicle-stimulating hormone (FSH) levels.
In addition, the release of a cascade of local growth factors such as insulin-like growth factors interacting with FSH, following a surgery-mediated increase in ovarian blood in response to thermal injury, has been suggested to allow follicular growth and subsequent ovulation. Further possible mechanisms are the decrease in anti-Müllerian hormone (AMH) concentrations and the production of “holes” in the very thick cortical wall of the polycystic ovary.
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Benefits of Ovarian Drilling
Hormonal Balance Improvement
Laparoscopic ovarian drilling significantly improves hormonal balance in clomiphene-resistant PCOS patients. A major objective of ovarian drilling is the normalization of the hormonal imbalance typically seen in women with PCOS, including the high LH/FSH ratio and hyperandrogenism. Studies have shown significant reductions in LH and testosterone levels following the procedure.
In a prospective study, significant reductions were observed in:
- AMH levels: 16% at 3 months, 25% at 6 months
- LH levels: 28% at 3 months, 35% at 6 months
- Testosterone levels: 30% at 3 months, 33% at 6 months
The significant reduction in testosterone levels reflects the positive impact of ovarian drilling on hyperandrogenism, a characteristic feature of PCOS that leads to symptoms such as hirsutism and acne. On the other hand, FSH levels remained stable, consistent with previous research showing that ovarian drilling primarily affects LH and testosterone, with FSH levels largely unaffected.
Restoration of Ovulatory Function and Menstrual Regularity
Ovarian drilling is effective in improving fertility outcomes in women with PCOS. A significant percentage of patients experience spontaneous ovulation and return to regular menstrual cycles after the procedure. In the aforementioned prospective study:
- Ovulation was restored in 78% of patients.
- Menstrual regularity returned in 72% of participants within 6 months post ovarian drilling.
These findings highlight the efficacy of ovarian drilling in improving ovulation and fertility rates in women with PCOS.
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Advantages over Medical Treatment
The surgical approach has some advantages in comparison to medical treatment. No significant differences were found with respect to live birth rate and miscarriage between LOD and gonadotropins or other medical treatment in women resistant to CC, with the advantage of spontaneous mono-ovulation without the need for intensive monitoring in order to minimize the risks of multiple pregnancies or OHSS. The increased responsiveness of the ovary to CC or gonadotropin medical therapy after LOD failure can be of invaluable help before proceeding to assisted reproductive therapy, mainly in vitro fertilization (IVF). LOD is considerably less expensive than ovulation induction with gonadotropins: a single treatment results in several mono-ovulatory cycles, whereas one course of gonadotropin therapy yields a single ovulatory cycle with an inherent cost for intensive monitoring. Finally, the aforementioned lower cycle cancellation rates in patients later submitted to IVF as well as the reduced incidence of OHSS contribute to lessening indirect costs. The risk of multiple pregnancies after LOD is lower than for gonadotrophin stimulation.
Second-Line Treatment
LOD may be considered in women with CC-resistant PCOS, particularly when there are other indications for laparoscopy, if there is a high risk of multiple pregnancies or a contra-indication of multiple pregnancies. All meta-analysis confirmed that LOD is a second-line treatment in PCOS patients, especially those with CC resistance. The main benefits are shorter time to pregnancy and less need to ovulation induction drugs.
Reduced Risk of Multiple Pregnancies and OHSS
Unlike fertility medicines, ovarian drilling is less likely to result in multiple pregnancies. This is a significant advantage, as multiple pregnancies carry increased risks for both the mother and the babies. Furthermore, studies have reported that LOD prior to ART is beneficial in decreasing the risk of severe OHSS and increasing the “take home baby “ rate in women who have previously had canceled IVF cycles due to OHSS risk or who suffered from OHSS in a previous treatment.
Risks and Considerations
Reduction in Ovarian Reserve
Concerns have been raised regarding the potential adverse effect of drilling on ovarian reserve. Ovarian reserve, typically assessed using anti-Mullerian hormone (AMH) and antral follicle count (AFC), reflects the remaining reproductive lifespan and fertility potential of a woman. Previous studies reported reductions in ovarian reserve following ovarian drilling, indicating a trade-off between short-term fertility benefits and potential long-term fertility risks.
The decrease in Anti-Mullerian Hormone levels observed in participants is consistent with the expected outcomes following ovarian drilling. AMH is a key marker of ovarian reserve, and a 25% reduction in AMH by 6 months post-surgery indicates a loss of follicles, a common consequence of the ovarian tissue destruction caused by ovarian drilling. While laparoscopic ovarian drilling is a successful short-term intervention for women with clomiphene citrate resistant PCOS, it should be noted that the reduction in ovarian reserve could be a concern for women who wish to delay pregnancy or who may want to preserve their fertility.
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Surgical Morbidity and Adhesion Formation
Among the possible adverse effects, surgical morbidity of this procedure should not be underestimated since it is frequently performed in overweight or obese women. In addition, specific concerns exist regarding the eventuality of iatrogenic adnexal adhesions and the reduction in ovarian reserve. The rate of adnexal adhesions differs widely in various studies ranging from 19 to 60%, mostly consisting of mild to moderate severity that seems to not affect pregnancy. However, due to this potential risk, LOD should be performed by fully trained laparoscopic surgeons, thereby reducing the likelihood of thermal damage, risk of adhesion, or injury to the neighboring viscera.
Other Risks
As with all surgical procedures, there are risks of bleeding, anesthesia, and infection. Also, as with any laparoscopic surgeries, the procedure can cause injury to the bowel, bladder, and blood vessels. Very rarely, there is a risk of death. If there is too much damage to the ovary during the ovarian drilling procedure, a woman may enter menopause at a younger age than expected. Accidental injury to internal organs or major blood vessels can occur.
Factors Influencing Success
Several prognostic factors predict successful outcomes and should be considered before choosing this surgical option. Factors increasing the efficacy of this technique are a normal body mass index (BMI), high LH concentration (>10 UI/L), short infertility duration, and age less than 35. Patients with BMI values greater than 35 kg/m2 obtain lower ovulation rates (13%) compared to patients with BMI between 29 and 34 kg/m2 (46%) and those with BMI < 29 kg/m2 (57%). Possible predictors of poor outcomes are hyperinsulinemia, elevated AMH levels and high testosterone serum levels.
Surgical Technique and Energy Source
Different types of energy sources and methods are reported in the literature for the accomplishment of the procedure: monopolar diathermy, using an insulated unipolar needle electrode with a non-insulated distal end measuring 1-2 cm, is the most widely used technique, although few authors have reported similar ovulation and pregnancy rates with a monopolar hook electrode or bipolar energy. The use of the harmonic scalpel was found in a randomized study to be just as effective as the Nd-YAG laser, although the latter has been found to be more prone to preventing adhesion owing to lower thermal penetration by the cone-shaped lesions of laser drilling.
Lack of consensus exists regarding the amount of electrosurgical energy and the optimal number of punctures holes to achieve maximum efficacy: reducing the thermal energy (<300 J/ovary) reduces the chances of ovulation and pregnancy, while higher thermal doses (>1000 J/ovary) may result in extensive tissue destruction without additional improvement in outcomes. Regarding the puncture holes, so far, it has been established that the administration of only two punctures in each ovary is insufficient to induce ovulation and more than eight punctures increase the occurrence of postoperative pelvic adhesions and ovarian reserve damage; it is inconclusive whether there is a difference in relation to clinical and reproductive outcome following greater than four ovarian punctures in each ovary. To date, it can be assumed that the ovulatory and pregnancy rate is dose-dependent up to a maximum thermal energy of 640 J/ovary, which can, therefore, be considered the lowest amount for effective diathermy.
Unilateral vs. Bilateral Ovarian Drilling
Unilateral ovarian drilling (ULOD) has been proposed as a modification of the standard LOD methodology with encouraging results. ULOD induces activity in both ovaries and minimizes procedure time; the lack of significant differences in terms of clinical and biochemical response, ovulation rate, and pregnancy rate if compared with conventional bilateral LOD (BLOD) let us consider this technique suitable for CC-resistant PCOS. At the moment, due to the paucity of available studies, it is uncertain if the equivalent reproductive outcome is associated with a lower risk of post-operative adhesions and ovarian reserve damage and, therefore, more studies are warranted before this technique.