1.Introduction
Polycystic ovarian syndrome (PCOS) is a common endocrine disorder with a prevalence of 6%-8% in women of reproductive age and is the most common cause of anovulatory infertility (about 75%). The diagnosis is based on clinical manifestations (obesity, menorrhagia/amenorrhea, hirsutism), biochemical changes (elevated serum luteinizing hormone and androgen levels) and ultrasonographic features (polycystic enlargement of ovaries), and insulin resistance and compensatory hyperinsulinemia may also be present in PCOS patients. In patients with anovulation due to PCOS, clomifene citrate (CC) is the first-line ovulatory drug. In patients with anovulation despite CC-resistance, or in patients who resume ovulation after CC but fail to conceive, laparoscopic ovarian drilling (LOD), gonadotropin ovulation promotion or metformin may be used. The choice of modality remains highly controversial and the advantage of L0D is that it is a simple, safe and effective method of ovulation induction in CC resistant/ineffective patients. This article will outline the current status, technique, clinical prognosis, possible mechanisms of action, complications and predictors of success of LOD in the treatment of patients with anovulatory PCOS.
2. Current status of laparoscopy in the treatment of PCOS
Currently, all overweight and obese PCOS patients should first be advised to lose weight by improving their lifestyle before any treatment is undertaken.CC remains the first-line treatment for anovulatory PCOS patients, while second-line treatment options are LOD or gonadotropin for ovulation. Although the choice of these 2 treatments remains controversial, LOD has many advantages over gonadotropin therapy. Importantly, in contrast to gonadotropin therapy, LOD treatment results in a single ovulation without the risk of ovarian hyperstimulation syndrome (OHSS) and the incidence of multiple pregnancies is not higher than in the general population . The main disadvantage of LOD is that it requires general anesthesia and surgical operation, and complications such as medical adhesion formation and premature ovarian failure are very rare and of little clinical significance.
3. Laparoscopic ovarian perforation methods
A variety of laparoscopic surgical methods have been reported in the literature for the treatment of anovulatory PCOS patients to induce ovulation. Methods include the application of electrocautery or laser, ovarian biopsy or multiple small holes in the surface of the ovarian tissue. Recently, a number of clinicians have experimented with transvaginal injection laparoscopy or ultrasound-guided ovarian perforation. Currently, the most widely used procedure is laparoscopic ovarian perforation (1aparoscopic ovarian diathermy, LOD). The method is as follows: ① Three operating holes are made in the abdominal wall to establish a pneumoperitoneum laparoscope, and the pelvic cavity is thoroughly examined to exclude organic disease and to check whether the ovaries show polycystic-like changes. A monopolar electro-needle (Roekett Ovarian Electro-needle, London) was used for ovarian perforation with a distal length of 8 mm and a diameter of 2 mm and a tapered insulated base with a maximum diameter of 6 mm. When the needle was inserted into the ovarian envelope, the insulated base prevented excessive needle penetration and minimized thermal damage to the ovarian tissue surface. ② The ovary is lifted and secured away from the intestine by applying a noninvasive grasping forceps to the intrinsic ligament of the ovary. This is important to avoid direct or indirect thermal injury to the intestinal canal. (iii) The electro-needle should be pierced in a vertical direction from the ovarian surface opposite the ovarian tract to avoid slippage and to minimize thermal damage to the ovarian tissue surface. The perforation should be positioned away from the ovarian hilum and the fallopian tube. This is necessary to avoid damage to the ovarian hilum (which may lead to ovarian atrophy) and the fallopian tubes (which may lead to mechanical infertility). ④ Electroacupuncture is applied to the ovarian envelope and perforated by monopolar electrocoagulation, operating at 3O w for 5 s. The current should not be activated before the electroacupuncture is applied to the ovarian surface to avoid perforation of the ovarian surface and to minimize damage to the ovarian surface due to the carbonation effect, which may cause adhesion formation later on. Brief electrocoagulation facilitates the penetration of the electro-needle. ⑤ Before putting the ovary back in place, a rinse with sodium lactate Ringer’s solution is applied to help cool the ovary.
4. Energy applied for the LOD procedure
The thermal energy and the number of holes perforated per ovary varies in different studies (3 to 15 holes). In a recent study on energy selection, a “high-low design” was used and the optimal number of holes per side of the ovary was found to be 4, with a perforation power of 30 w per hole and a time of 5 s (150 J).
5. Clinical prognosis of LOD
5.1 Short-term prognosis
A rapid response has been reported after LOD, with ovulation resuming within 2-4 weeks and menstruation resuming within 4-6 weeks in 70%-80% of cases. 37% of pregnancies were observed after LOD, and the pregnancy rate rose to 55% after the addition of cc in patients who still did not ovulate. The main hormonal changes observed after LOD are a rapid and sustained decrease in serum androgen levels (testosterone and androstenedione) and a transient increase in gonadotropin (LH and FSH) levels 24-48 h after surgery, followed by a gradual decrease.
5.2 Long-term prognosis
The beneficial clinical and endocrine effects of LOD appear to persist for many years (up to 20 years) in a significant proportion of patients with PCOS. A recent long-term follow-up of 116 anovulatory PCOS patients who received LOD showed that improvements in endocrine parameters, menstrual cycle and fertility lasted for many years in 1/3 of the patients.
6. Mechanism of action of LOD
At present, the mechanism of action of LOD cannot be explained, but it seems that LOD exerts its effect by destroying the androgen-producing tissues of the ovary. The decrease in circulating androgen concentration leads to a decrease in peripheral androgen aromatization, a decrease in estrone (E1) levels, and the restoration of normal LH positive feedback with FSH negative feedback. Elevated postoperative FSH levels may increase aromatase activity in the follicles. These effects, together with the reduction in local androgen levels, combine to change the intrafollicular environment from androgen-dominant to estrogen-dominant, removing barriers to follicular maturation in the ovary and allowing follicles to recruit, develop and ovulate. It has also been suggested that damage to the ovary results in the production of nonsteroidal factors that affect ovarian-pituitary feedback. More recently, it has been hypothesized that in response to tissue damage, the ovaries produce many growth factors (e.g., IGF.I) that sensitize the ovaries to circulating FSH and thus stimulate follicle growth.
7. Predictors of LOD prognosis
Recently, we looked at various clinical or biochemical indicators that may predict prognosis in a study of 200 cases undergoing LOD. It was shown that severe obesity (BMI ≥35 kg/m ), severe hyperandrogenemia (testosterone ≥4.5 nmol/L or free androgen index (FAI) ≥15), and/or prolonged infertility (>3 years) seemed to predict ineffective LOD. Ovulation and pregnancy rates after LOD were higher in patients with preoperative hyper-LHemia (≥10 IU/L). Age, presence of comorbid acne, menstrual cycle status, LH/FHS and ovarian volume do not seem to be predictive of prognosis after LOD .
8. Complications of laparoscopic ovarian perforation
Intraoperative complications of LOD are rare and include injury to the ligamentous ligament of the ovary/bleeding at the ovarian perforation site/heat injury to the intestinal canal and postoperative complications of medically induced adhesion formation. The incidence reported in different studies is 30-40%. Only mild or moderate adhesions have been reported in most studies and do not seem to affect the pregnancy rate after LOD. All measures should be taken to reduce the formation of adhesions. Methods include reducing thermal damage to the ovarian surface. As mentioned above, large amounts of fluid are flushed and crystalloid is instilled at the end of the procedure. Another theoretical LOD-associated risk is premature ovarian failure, which results from excessive destruction of normal follicular tissue or disruption of the ovarian blood supply. In our cohort study including 116 cases of PCOS with a maximum follow-up up to 9 years after LOD, no cases of premature ovarian failure were observed. The risk of premature ovarian failure can be greatly reduced by reducing the number of perforations and by performing the operation away from the ovarian portal.
9. Failure of laparoscopic ovarian surgery
If the patient fails to ovulate or resume regular ovulation within 6-8 weeks after LOD, and fails to have a pregnancy within 12 months or has anovulation again, the operation is considered a failure. For patients with anovulation, CC can be applied again. many studies have shown that LOD can improve the sensitivity of the ovaries to CC. If the patient is still anovulatory after CC, the treatment options are: (1) gonadotropin ovulation treatment; (2) metformin; (3) IVF; and (4) LOD again. we have reported a high success rate of LOD again in patients who had an effect of the initial LOD procedure. On the other hand, for patients with no effect of previous LOD, repeat LOD remains ineffective.
10. Conclusion
LOD is a second-line treatment for patients with CC-resistant PCOS. it is as effective as gonadotropin ovulation, and has the advantage of avoiding the risk of multiple pregnancies and OHSS. The most widely used procedure is laparoscopic monopolar electro-acupuncture ovarian perforation. the appropriate energy for LOD is 4 perforations per ovary, with a solenoid power of 30 w and a time of 5 S. About 2/3 of patients recover ovulation after LOD. 50% of patients who recover ovulation, i.e. 1/3 of all patients who undergo the procedure, will continue to benefit for years to come. the main disadvantages of LOD are the need for general anesthesia, adhesion formation and the theoretical risk of premature ovarian failure. The main disadvantages of LOD are the need for general anesthesia, adhesion formation and the theoretical risk of premature ovarian failure.