Oocyte vitrification in the 21st century and post-warming fertility outcomes: a systematic review and meta-analysis.

Oocyte cryopreservation is a rapidly developing technology, which is increasingly being used for various medical, legal and social reasons. There are inconsistencies in information regarding survival rate and fertility outcomes. This systematic review and meta-analysis provides evidence-based information about oocyte survival and fertility outcomes post warming to help women to make informed choices. All randomized and non-randomized, controlled and prospective cohort studies using oocyte vitrification were included. The primary outcome measure was ongoing pregnancy rate/warmed oocyte. Sensitivity analysis for donor and non-donor oocyte studies was performed. Proportional meta-analysis of 17 studies, using a random-effects model, showed pooled ongoing pregnancy and clinical pregnancy rates per warmed oocyte of 7%. Oocyte survival, fertilization, cleavage, clinical pregnancy and ongoing pregnancy rates per warmed oocyte were higher in donor versus non-donor studies. Comparing vitrified with fresh oocytes, no statistically significant difference was observed in fertilization, cleavage and clinical pregnancy rates, but ongoing pregnancy rate was reduced in the vitrified group (odds ratio 0.74), with heterogeneity between studies. Considering the age of women and the reason for cryopreservation, reasonable information can be given to help women to make informed choices. Future studies with outcomes from oocytes cryopreserved for gonadotoxic treatment may provide more insight.

FSH receptor genotype does not predict metaphase-II oocyte output or fertilization rates in ICSI patients.

The objective of this study was to assess the role of the variant p.Asn680Ser in the FSH receptor gene (FSHR) in determining oocyte maturity. It also assessed the relationship between this FSHR variant with metaphase-II oocyte output rate (MOR) and the fertilization rate. This was a prospective observational study based at a tertiary referral centre for reproductive medicine. Women (n=212) undergoing their first cycle of ovarian stimulation for IVF with intracytoplasmic sperm injection (ICSI) were included in the study. Baseline pelvic ultrasound and blood tests were taken on day 2 or 3 of the cycle for assessment of baseline hormones and for DNA extraction. Genotypes for FSHR p.Asn680Ser was determined using TaqMan allelic discrimination assay. The outcome measures were the total dose of exogenous gonadotrophins used, antral follicle count (AFC), number of mature (metaphase-II) oocytes retrieved, MOR and fertilization rate. No statistically significant differences were found between the number of mature oocytes retrieved, MOR or fertilization rates among the patients with different p.Asn680Ser FSHR genotypes. No significant difference was noted in the clinical pregnancy rates per transfer. There is no evidence that the p.Asn680Ser FSHR genotype predicts oocyte maturity.

Anti-Mullerian hormone: poor assay reproducibility in a large cohort of subjects suggests sample instability.

STUDY QUESTION: What is the variability of anti-Müllerian hormone (AMH) concentration in repeat samples from the same individual when using the Gen II assay and how do values compare to Gen I [Diagnostic Systems Ltd (DSL)] assay results? SUMMARY ANSWER: The Gen II AMH assay displayed appreciable variability, which can be explained by sample instability. WHAT IS KNOWN ALREADY: AMH is the primary predictor of ovarian performance and is used to tailor gonadatrophin dosage in cycles of IVF/ICSI and in other routine clinical settings. Thus, a robust, reproducible and sensitive method for AMH analysis is of paramount importance. The Beckman Coulter Gen II ELISA for AMH was introduced to replace earlier DSL and Immunotech assays. The performance of the Gen II assay has not previously been studied in a clinical setting. STUDY DESIGN, SIZE AND DURATION: We studied an unselected group of 5007 women referred for fertility problems between 1 September 2008 and 25 October 2011; AMH was measured initially using the DSL AMH ELISA and subsequently using the Gen II assay. AMH values in the two assays were compared using a regression model in log(AMH) with a quadratic adjustment for age. Additionally, women (n = 330) in whom AMH had been determined in different samples using both the DSL and Gen II assays (paired samples) identified and the difference in AMH levels between the DSL and Gen II assays was estimated using the age-adjusted regression analysis. A subset of 313 women had repeated AMH determinations (n = 646 samples) using the DSL assay and 87 women had repeated AMH determinations using the Gen II assay (n = 177 samples) were identified. A mixed effects model in log(AMH) was utilized to estimate the sample-to-sample (within-subject) coefficients of variation of AMH, adjusting for age. Laboratory experiments including sample stability at room temperature, linearity of dilution and storage conditions used anonymized samples. MAIN RESULTS AND THE ROLE OF CHANCE: In clinical practice, Gen II AMH values were ∼20% lower than those generated using the DSL assay instead of the 40% increase predicted by the kit manufacturer. Both assays displayed high within-subject variability (Gen II assay CV = 59%, DSL assay CV = 32%). In the laboratory, AMH levels in serum from 48 subjects incubated at RT for up to 7 days increased progressively in the majority of samples (58% increase overall). Pre-dilution of serum prior to assay, gave AMH levels up to twice that found in the corresponding neat sample. Pre-mixing of serum with assay buffer prior to addition to the microtitre plate gave higher readings (72% overall) compared with sequential addition. Storage at -20°C for 5 days increased AMH levels by 23% compared with fresh samples. The statistical significance of results was assessed where appropriate. LIMITATIONS, REASONS FOR CAUTION: The analysis of AMH levels is a retrospective study and therefore we cannot entirely rule out the existence of differences in referral practices or changes in the two populations. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggests that AMH may not be stable under some storage or assay conditions and this may be more pronounced with the Gen II assay. The published conversion factors between the Gen II and DSL assays appear to be inappropriate for routine clinical practice. Further studies are urgently required to confirm our observations and to determine the cause of the apparent instability. In the meantime, caution should be exercised in the interpretation of AMH levels in the clinical setting. CONFLICT OF INTEREST/STUDY FUNDING: S. Roberts is supported by the NIHR Manchester Biomedical Research Centre.

Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis.

Mechanical endometrial injury (biopsy/scratch or hysteroscopy) in the cycle preceding ovarian stimulation for IVF has been proposed to improve implantation in women with unexplained recurrent implantation failure (RIF). This is a systematic review and meta-analysis of studies comparing the efficacy of endometrial injury versus no intervention in women with RIF undergoing IVF. All controlled studies of endometrial biopsy/scratch or hysteroscopy performed in the cycle preceding ovarian stimulation were included and the primary outcome measure was clinical pregnancy rate. Pooling of seven controlled studies (four randomized and three non-randomized), with 2062 participants, showed that local endometrial injury induced in the cycle preceding ovarian stimulation is 70% more likely to result in a clinical pregnancy as opposed to no intervention. There was no statistically significant heterogeneity in the methods used, clinical pregnancy rates being twice as high with biopsy/scratch (RR 2.32, 95% CI 1.72-3.13) as opposed to hysteroscopy (RR 1.51, 95% CI 1.30-1.75). The evidence is strongly in favour of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained RIF. However, large randomized studies are required before iatrogenic induction of local endometrial injury can be warranted in routine clinical practice. Some women undergoing IVF treatment fail to conceive despite several attempts with good-quality embryos and no identifiable reason. We call this 'recurrent implantation failure' (RIF) where the embryo fails to embed or implant within the lining of the womb. Studies have shown that inducing injury to the lining of the womb in the cycle before starting ovarian stimulation for IVF can help improve the chances of achieving pregnancy. Injury can be induced by either scratching the lining of the womb using a biopsy tube or by telescopic investigation of the womb using a camera. We performed a collective review of the available good-quality studies that used the above two methods in the cycle prior to starting ovarian stimulation for IVF. We pooled results from seven studies, which included 2062 women with RIF and assessed the difference in clinical pregnancy rates for those undergoing injury to the womb lining compared with no injury prior to IVF. The results suggest that inducing injury is 70% more likely to result in a clinical pregnancy as opposed to no treatment. Furthermore, scratching of the lining was 2-times more likely to result in a clinical pregnancy compared with telescopic evaluation of the lining of the womb. This study suggests that in women with RIF, inducing local injury to the womb lining in the cycle prior to starting ovarian stimulation for IVF can improve pregnancy outcomes. However, large studies are required before this can be warranted in routine clinical practice.

PCOS and peripheral AMH levels in relation to FSH receptor gene single nucleotide polymorphisms.

OBJECTIVES: To determine if an association exists between the follicle-stimulating hormone receptor (FSHR) gene p.Asn680Ser polymorphism and polycystic ovary syndrome (PCOS) or with high anti-mullerian hormone (AMH) levels without PCOS. PATIENTS: Fifty-eight women with PCOS, 24 women with high AMH (>44.5 pmol/L) without PCOS and 80 healthy ethnically matched female controls. MAIN OUTCOME MEASURES: Prevalence of the FSHR p.Asn680Ser polymorphism, baseline serum AMH levels and response to ovulation induction with clomiphene citrate. RESULTS: The frequency of FSHR p.Asn680Ser genotypes were not significantly different between PCOS patients, patients with high AMH without PCOS and controls (p = 0.88). Of the women with PCOS, 34/58 were on clomiphene citrate treatment and 12/34 were resistant. There was no association between sensitivity or resistance to clomiphene and p.Asn680Ser genotypes (p = 0.38). CONCLUSIONS: There is no evidence that FSHR p.Asn680Ser genotypes are associated with PCOS, high AMH levels or response to clomiphene citrate.

Evidence-based management of endometrioma.

Endometrioma is commonly seen in women of reproductive age who may wish to preserve their ovarian function. Surgical treatment is associated with a high recurrence rate and its employment for women undergoing assisted conception has recently been challenged. Medical treatment has not been shown to be effective in controlling symptoms or improving fertility potential. The results of retrospective and non-randomized studies have been inconsistent and created an ongoing debate between gynaecologists and fertility specialists. This manuscript reviews and critically appraises the evidence for management of endometrioma in women of reproductive age. In asymptomatic women, surgical treatment is usually recommended for women above the age of 40 and for large endometriomas. Except for pelvic clearance, there is insufficient evidence to suggest that surgical treatment of endometrioma is better than medical treatment with respect to the long-term relief of symptoms and quality of life. Laparoscopic excision of ovarian endometrioma prior to IVF does not offer any additional benefit over expectant management. A large, well-designed, adequately powered randomized controlled study that compares the effects of surgical removal versus expectant management of endometrioma on ovarian performance and pregnancy outcomes in women undergoing IVF is warranted.

Conventional ovarian stimulation no longer exists: welcome to the age of individualized ovarian stimulation.

The prediction of extremes of ovarian response to stimulation and the irreversibility of reduced ovarian reserve remain important clinical and basic science research issues of IVF treatment. Recommending commencement of ovarian stimulation using any of the available exogenous compounds without knowledge of individual ovarian potentials is simplistic and dangerous because of the possible adverse consequences for the woman. The identification of groups of patients likely to benefit from one protocol than another is central to the workup process of IVF. Determining the agents for ovarian stimulation as well as the combination of them, the daily dose and duration according to some background information should be seen as the way to enhance safety and cost-effectiveness. This discussion paper aims to introduce the concept of individualized ovarian stimulation in routine clinical practice and to generate interest for tailored stimulation protocols.

Optimizing hormone therapy for future reproductive performance in women with premature ovarian failure.

With increasing success in treatment of childhood cancer there is a growing population of women with premature ovarian failure (POF) seeking fertility treatment. Various preparations of estrogen and progestogen are prescribed for young women with POF. While the dose and duration of hormone therapy (HT) is usually adjusted according to the patient's height and the Tanner's stage of development for young pre-pubertal women, the optimal effective HT regimen to maximise the reproductive potential for young as well as for the older age group remains unclear. Furthermore, there is a paucity of evidence to support the preferential effectiveness of the different regimens used. Assisted reproduction using donated gametes or embryos remains the only realistic option to enable women with POF to conceive. Successful outcomes are primarily dependant on successful implantation and placentation. Consequently, the success of assisted reproduction is determined by uterine and endometrial development, which is largely influenced by the modality of HT as well as the age at which it is commenced. In this review, we critically appraise the current practices and published data for management of women with POF. We aim to focus on the effect of HT on uterine development in women with primary and irreversible POF.

Management of endometrioma prior to IVF: compliance with ESHRE guidelines.

Management of endometrioma before IVF remains controversial. As well as some measurable benefits from surgical treatment, there are also potential risks that should be discussed with the patients to help them make an informed decision. When surgery is compared with expectant management, there appear to be no statistically significant differences in pregnancy rate and ovarian response to exogenous stimulation. The objectives of this European Society of Human Reproduction and Embryology (ESHRE)-sponsored survey were to acquire knowledge of current strategies for the management of endometrioma (>3 cm) prior to IVF and to explore adherence to ESHRE guidelines. A validated, peer-reviewed online questionnaire made of 14 questions was sent to 396 members of the ESHRE Special Interest Groups (Reproductive Surgery and Endometriosis/Endometrium), with a response rate of 27%. Surgical management is the most common treatment (82.2%), with drainage and excision of the cyst wall being the preferred surgical approach (78.5%). Monthly depot gonadotrophin-releasing hormone analogues are the preferred choice of medical treatment of endometriomas before IVF, with an average duration of treatment of 3 months. The findings demonstrate that surgery remains the commonest treatment offered for women with endometrioma before IVF. This is in line with the recommendations of the ESHRE guidelines.

Growth hormone for in vitro fertilization.

BACKGROUND: In an effort to improve outcomes of in-vitro fertilisation cycles the use of growth hormone has been considered. Improving the outcomes of in-vitro fertilisation is especially important for subfertile women who are considered 'poor responders'. OBJECTIVES: To assess the effectiveness of adjuvant growth hormone in in-vitro fertilisation protocols. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Groups trials register (June 2009), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2, 2009), MEDLINE (1966 to June 2009), EMBASE (1988 to June 2009) and Biological Abstracts (1969 to June 2009). SELECTION CRITERIA: All randomised controlled trials were included if they addressed the research question and provided outcome data for intervention and control participants. DATA COLLECTION AND ANALYSIS: Assessment of trial risk of bias and extraction of relevant data was performed independently by two reviewers. MAIN RESULTS: Ten studies (440 subfertile couples) were included. Results of the meta-analysis demonstrated no difference in outcome measures and adverse events in the routine use of adjuvant growth hormone in in-vitro fertilisation protocols. However, meta-analysis demonstrated a statistically significant difference in both live birth rates and pregnancy rates favouring the use of adjuvant growth hormone in in-vitro fertilisation protocols in women who are considered poor responders without increasing adverse events, OR 5.39, 95% CI 1.89 to 15.35 and OR 3.28, 95% CI 1.74 to 6.20 respectively. AUTHORS' CONCLUSIONS: Although the use of growth hormone in poor responders has been found to show a significant improvement in live birth rates, we were unable to identify which sub-group of poor responders would benefit the most from adjuvant growth hormone. The result needs to be interpreted with caution, the included trials were few in number and small sample size. Therefore, before recommending growth hormone adjuvant in in-vitro fertilisation further research is necessary to fully define its role.

Adjuvants in IVF-evidence for what works and what does not work.

The field of assisted reproductive technology is shaped and changed constantly by advances in science and cutting-edge innovations. In a quest to maximise outcomes, add-on interventions are often adopted and utilised prematurely while the principles of evidence-based medicine seem to be less strictly adhered to. In this review we will attempt to summarise the latest evidence about some of the adjuvants.

The relationships between AMH, androgens, insulin resistance and basal ovarian follicular status in non-obese subfertile women with and without polycystic ovary syndrome.

BACKGROUND: Hyperandrogenaemia and insulin resistance are prominent features of polycystic ovary syndrome (PCOS) and influence the process of folliculogenesis in women with the endocrinopathy. Anti-Müllerian hormone (AMH) levels are elevated in women with PCOS and studies including IVF subjects have shown that this is a reliable marker of ovarian performance. The aims of this prospective study were to assess the relationship between insulin resistance, androgens and AMH, and whether AMH contributes to altered folliculogenesis in non-obese women with PCOS. METHODS: A total of 232 IVF candidates, 49 of whom had PCOS according to the Rotterdam 2003 consensus criteria, were recruited. AMH levels and ovarian morphology were assessed. The relationships between AMH and insulin resistance and androgenaemia in patients with and without PCOS were studied. RESULTS: PCOS patients were slightly older than controls (median ages 34 and 30 years, respectively). AMH generally increased with antral follicle count (AFC), insulin, homeostatic model assessment of tissue insulin sensitivity (HOMA-IR), testosterone, free androgen index and luteinising hormone, and decreased with chronological age, homeostatic model assessment of steady state beta cell function (HOMA-B) and serum sex hormone binding globulin (SHBG). For these relationships there were no significant differences in the slopes between PCOS and non-PCOS patients. The ratio of AMH per antral follicle (AMH/AF) was higher in PCOS patients. Both PCOS and non-PCOS groups showed a very similar increase in AMH with increases in AFC, but the PCOS patients had consistently higher AMH across all AFC levels. CONCLUSIONS: These observations indicate that AMH is similarly related to insulin resistance and androgens in women with and without PCOS. This effect appears to be independent of age although an indirect causal effect due to ageing or some other mechanism cannot be ruled out. Excessive granulosa cell activity may be implicated in the abnormal follicular dynamic of the syndrome.

Symposium: Update on prediction and management of OHSS. Optimal dose of HCG for final oocyte maturation in IVF cycles: absence of evidence?

There is an ongoing debate over the optimal dose of urinary HCG (u-HCG) that can trigger final oocyte maturation, leading to higher IVF success rate without increasing the risk of ovarian hyperstimulation syndrome (OHSS). A systematic review was conducted of all studies that compared the effect of at least two doses of u-HCG for final oocyte maturation on IVF outcomes and on the incidence of OHSS. The primary outcome was the live birth rate, and the secondary end-points were the number of oocytes retrieved, fertilization, implantation and pregnancy rates, and the incidence of OHSS. Only two amongst the six included studies were randomized controlled trials (RCT). Meta-analytic pool was not feasible due to insufficient number of studies assessing the same outcome and significant heterogeneity. The majority of studies concluded that the clinical outcomes were similar between women receiving 5000 or 10,000 IU of u-HCG. The incidence of OHSS was not reduced in the high-risk population even with lower dose of u-HCG. Until large scale RCT addressing the clinical effectiveness and the adverse outcomes related to various doses of u-HCG are conducted, the dose of u-HCG for final oocyte maturation for women referred for IVF needs to be individualized.

Growth hormone for in vitro fertilization.

BACKGROUND: In an effort to improve outcomes of in-vitro fertilisation cycles the use of growth hormone has been considered. Improving the outcomes of in-vitro fertilisation is especially important for subfertile women who are considered 'poor responders'. OBJECTIVES: To assess the effectiveness of adjuvant growth hormone in in-vitro fertilisation protocols. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Groups trials register (June 2009), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2, 2009), MEDLINE (1966 to June 2009), EMBASE (1988 to June 2009) and Biological Abstracts (1969 to June 2009). SELECTION CRITERIA: All randomised controlled trials were included if they addressed the research question and provided outcome data for intervention and control participants. DATA COLLECTION AND ANALYSIS: Assessment of trial risk of bias and extraction of relevant data was performed independently by two reviewers. MAIN RESULTS: Ten studies (440 subfertile couples) were included. Results of the meta-analysis demonstrated no difference in outcome measures and adverse events in the routine use of adjuvant growth hormone in in-vitro fertilisation protocols. However, meta-analysis demonstrated a statistically significant difference in both live birth rates and pregnancy rates favouring the use of adjuvant growth hormone in in-vitro fertilisation protocols in women who are considered poor responders without increasing adverse events, OR 5.39, 95% CI 1.89 to 15.35 and OR 3.28, 95% CI 1.74 to 6.20 respectively. AUTHORS' CONCLUSIONS: Although the use of growth hormone in poor responders has been found to show a significant improvement in live birth rates, we were unable to identify which sub-group of poor responders would benefit the most from adjuvant growth hormone. The result needs to be interpreted with caution, the included trials were few in number and small sample size. Therefore, before recommending growth hormone adjuvant in in-vitro fertilisation further research is necessary to fully define its role.

Medical adjuncts in IVF: evidence for clinical practice.

The cross-talk between the embryo and the endometrium, leading to implantation, is a complex, dynamic and highly controlled phenomenon. Over the last decade, a large amount of translational and clinical research has been carried out in an attempt to increase the likelihood of pregnancy in in vitro fertilisation (IVF). The purpose of this article was to review the literature on the effectiveness of adjuvant therapy in IVF and to provide fertility professionals with evidence-based guidance and recommendations. Clinicians who decide to prescribe therapies for which the evidence base is weak, should make patients aware of this lack of knowledge and potential adverse effects. There is a need for good clinical trials in many of the areas surrounding medical adjuncts in IVF to resolve the empirical/evidence divide.

Anti-Müllerian hormone levels and antral follicle count in women enrolled in in vitro fertilization cycles: relationship to lifestyle factors, chronological age and reproductive history.

The aims of this prospective study were to investigate the relationship between anti-Müllerian hormone (AMH) and antral follicle count (AFC), and to determine whether these markers of ovarian reserve correlate with lifestyle factors, ethnicity, chronological age and reproductive history. Participants were 136 normo-ovulatory women undergoing infertility work-up within 3 months of their first ovarian stimulation cycle for in vitro fertilization. On day 3 of a spontaneous menstrual cycle, a blood sample for measurement of plasma AMH levels was taken and a transvaginal ultrasound scan to determine the AFC (follicles measuring 2-5 mm in diameter) was performed. Information about smoking, body mass index, alcohol consumption, ethnic origin, chronological age, age at menarche, years since menarche and gravidity were recorded using a case report form. The main outcome measures were plasma AMH concentrations and total number of small antral follicles (AFC). Median plasma levels of AMH were 2.0 ng/ml (interquartile range 1.1-3.6) and AFC was 10 (interquartile range 7-15). A positive correlation between AMH and AFC (r = 0.54, p < 0.0001) was found. AMH and AFC correlated negatively with age (r = -0.30, p < 0.001 and r = -0.27, p = 0.001 respectively) and number of years since menarche (r = -0.23, p = 0.007 and r = -0.21, p = 0.015 respectively), but not with any of the other measures. Circulating AMH levels and AFC correlated with each other and declined significantly with age. There were only weak, non-significant, correlations with lifestyle factors and reproductive history. These putative markers could be used individually or together to assess the age-related decline of ovarian function in normo-ovulatory candidates for IVF.

Ultrasonography in polycystic ovary syndrome: an update.

Polycystic ovary syndrome (PCOS) is a convergence of multisystem endocrine derangements. During the last decade, the role of ultrasonography in the diagnosis and monitoring of this endocrinopathy underwent significant changes. However, there remain many concerns about whether these changes should be more widely introduced in clinical practice. Current concepts include the use of high-resolution, 3-dimensional ultrasound instead of conventional 2-dimensional ultrasound; formulaic methods of measuring ovarian volume; and correlation between ultrasonographic features, biochemical indices and ovarian stromal changes, such as enhanced echogenicity and increased blood flow. These issues, together with the new Rotterdam 2003 European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine (ASRM)-sponsored consensus criteria for the diagnosis of PCOS, are discussed in this review article.

Reproductive outcome after laparoscopic treatment of minimal and mild endometriosis using Helica Thermal Coagulator.

OBJECTIVE: To investigate the reproductive outcome following Helica Thermal Coagulator (Helica TC) in an infertile population with early-stage endometriosis. DESIGN: A clinical observational trial conducted in a NHS tertiary referral centre for treatment of endometriosis. Forty-four healthy infertile women (mean age 21 years, range 18-34 years) with laparoscopically confirmed diagnosis of minimal (stage I) or mild (stage II) endometriosis were included. All visible endometriotic lesions and adhesions were treated using Helica TC at the same time of diagnostic laparoscopy. Following laparoscopy, women attempted to conceive spontaneously and were followed for 12 months or until delivery. No hormonal therapy for endometriosis was given whatsoever. RESULTS: One woman was lost to follow-up and the remaining 43 women were considered in the final analysis. The cumulative pregnancy rate was 23.2% (10/43). All pregnancies occurred spontaneously and neither miscarriages nor ectopic pregnancies were observed. Pregnancy rate did not differ between women with stage I and those with stage II endometriosis. The time-to-pregnancy was similar in women with different stage endometriosis. No surgical complications were encountered. CONCLUSIONS: These findings suggest that Helica TC is a simple and safe conservative laparoscopic surgery for early-stage endometriosis. Helica TC appears to improve reproductive outcome in women with otherwise unexplained infertility. Large RCTs are needed to define these preliminary data.