We looked at whether women who have clomiphene-resistant polycystic ovarian syndrome (PCOS) would benefit from applying ultrasound-guided transvaginal ovarian needle drilling (UTND) to induce ovulation.
Clomiphene citrate is one of the first-line treatments in inducing ovulation (release of an egg from the ovary) in women with PCOS. However, 15% to 40% of women do not ovulate after clomiphene administration (what we call clomiphene resistance). UTND, puncturing an ovary under the guidance of ultrasound, is used for women with clomiphene-resistant PCOS to assist releasing a dominant follicle (ovulation). Also, gonadotrophins, which are injectable hormonal medicines, can be offered as a treatment option to induce ovulation in women with clomiphene-resistant PCOS.
It has been suggested that compared to laparoscopic ovarian drilling (LOD), UTND may decrease the risk of surgical complications. Nevertheless, most of the studies of UTND have limitations in study methodology. Safety and efficacy of UTND are still uncertain.
We searched for studies published up to November 2018.
Five randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 639 women were included in the review. Three compared UTND to LOD, and two compared UTND combined with gonadotropins to gonadotropins.
UTND versus LOD
The quality of the three studies was low to very low. None of the studies reported on the main outcome of live birth. Based on currently available evidence, we are uncertain whether pregnancy rate of women using UTND is different from that of LOD. UTND may lead to a small decrease in ovulation rate when compared to LOD. Thus, low-quality evidence suggests that among clomiphene-resistant women with PCOS using LOD with an expected ovulation rate of 69.5%, the rate among women using UTND may be between 50.6% and 68.8%. There is insufficient evidence to reach conclusions regarding surgical complications and miscarriage, as we found only one very low-quality study. None of the studies reported OHSS or multiple pregnancy rate.
UTND combined with gonadotropins versus gonadotropins alone
We were unable to assess the benefit or harm of applying UTND combined with gonadotropins for women with clomiphene-resistant PCOS, as we identified only two very low-quality trials that used different doses of gonadotropins.
Quality of the evidence
We assessed the quality of the evidence as low to very low due to poor explanations of study methodology and the limited number of included trials. Also, reporting on clinically relevant issues that are important for subfertile couples, such as live birth, was lacking.
Based on very low-quality evidence, It is uncertain whether there is any difference in pregnancy rate, incidence of surgical complications, and miscarriage rate between UTND and LOD in women with clomiphene-resistant PCOS. UTND may lead to a slight decrease in ovulation rate when compared to LOD. No studies reported on the outcomes live birth rate, incidence of OHSS, and multiple pregnancy rate. No studies reported on the main outcomes live birth and surgical complications for the comparison UTND combined with gonadotrophins versus gonadotrophins alone. The evidence for the outcomes OHSS, pregnancy, ovulation, miscarriage, and multiple pregnancy in this comparison was of very low quality. Thus, it is unclear if there is a difference in any of the outcomes between UTND combined with gonadotrophins versus gonadotrophins alone.
Ovulatory disturbance is a key diagnostic feature of polycystic ovarian syndrome (PCOS), leading to infertility and correspondingly heavy disease burden. Many therapeutic strategies have been used to induce ovulation for women with PCOS who are infertile. Ultrasound-guided transvaginal ovarian needle drilling (UTND) is a novel surgical method used to induce ovulation for women with clomiphene-resistant PCOS at the outpatients clinic. Nevertheless, the quality in most of the studies seemed low, and the safety and efficacy of UTND is still uncertain.
To evaluate the efficacy and safety of UTND for subfertile women with clomiphene-resistant PCOS.
We searched the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, and six other databases to November 2018. We checked conference abstracts from the 2018 ESHRE, reference lists, and clinical trials registries. We contacted experts and specialists in the field.
We included randomised controlled trials (RCTs) comparing UTND to laparoscopic ovarian drilling (LOD), and UTND combined with gonadotropins to gonadotropins alone for women of reproductive age with clomiphene-resistant PCOS and infertility.
Two review authors independently screened appropriate trials for inclusion, assessed methodological quality and risk of bias, and extracted data. The primary outcomes were live birth rate and incidence of surgical complications (bleeding and infection). We included ovarian hyperstimulation syndrome (OHSS) as a secondary outcome. Meta-analyses could only be conducted for the secondary outcomes pregnancy rate and ovulation rate in the comparison of UTND versus LOD using a random-effect model. We calculated odds ratios (OR) with 95% confidence intervals (CI) for dichotomous data. We assessed the overall quality of the evidence by applying GRADE criteria.
We included five trials involving 639 clomiphene-resistant women with PCOS. Three studies compared UTND with LOD, and two compared UTND combined with gonadotropins with gonadotropins alone. The evidence was of low to very low quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency resulting from heterogeneity, imprecision induced by limited sample size, and lack of reporting of clinically relevant outcomes such as live birth and surgical complications.
UTND versus LOD
No studies reported on the main outcome live birth. One study reported on surgical complications; however, the evidence for this outcome was of very low quality because it was based on one study with small sample size and there were no events in either arm. Thus, we are uncertain whether there is any difference in surgical complications between UTND and LOD.
We are also uncertain whether there is any difference in pregnancy rate when comparing UTND with LOD (OR 0.54, 95% CI 0.28 to 1.03; I2 = 56%; 3 RCTs, n = 473; very-low quality evidence). UTND may lead to a slight decrease in ovulation rate when compared to LOD (OR 0.66, 95% CI 0.45 to 0.97; I2 = 0%; 3 RCTs, n = 473; low-quality evidence). This suggests that among clomiphene-resistant women with PCOS using LOD with an expected ovulation rate of 69.5%, the ovulation rate among women using UTND may be between 50.6% and 68.8%
No studies reported on the outcomes OHSS and multiple pregnancy. There was also insufficient evidence to reach a conclusion regarding miscarriage as there was only one study of very low quality.
UTND combined with gonadotropins versus gonadotropins alone
No studies reported on the main outcomes live birth and incidence of surgical complications. The evidence for the outcomes OHSS, pregnancy, ovulation, miscarriage, and multiple pregnancy in this comparison was of very low quality. Thus, we are uncertain whether there is any difference in these outcomes for women with clomiphene-resistant PCOS using UTND combined with gonadotropins as compared with gonadotropins.