Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Searching the Internet for Infertility Information: A Survey of Patient Needs and Preferences.

BACKGROUND: Given the complexity of infertility diagnoses and treatments and the convenience of the internet for finding health-related information, people undergoing infertility treatments often use Web-based resources to obtain infertility information and support. However, little is known about the types of information and support resources infertility patients search for on the internet and whether these resources meet their needs. OBJECTIVE: The aims of this study were to (1) examine what individual factors, namely, demographic characteristics and distress, are associated with searching the internet for different types of infertility-related information and support resources and (2) determine whether Web-based resources meet the needs of patients. METHODS: Men and women seeking infertility care responded to a survey assessing use of Web-based resources for accessing infertility-related information and support. The survey further assessed satisfaction with Web-based resources as well as perceived stress and depressive symptomatology. RESULTS: A total of 567 participants, including 254 men and 313 women, completed the survey. Most participants (490/558, 87.8%) had searched the internet for infertility information and support. Searchers were more likely to be women (P<.001), highly educated (P=.04), long-term patients (P=.03), and more distressed (P=.04). Causes of infertility, treatment options, and scientific literature about infertility were the three most frequently searched topics, whereas ways to discuss treatment with family and friends as well as surrogacy and ways to find peer support were the three least searched topics. Of those who searched the internet, 70.9% (346/488) indicated that their needs were met by Web-based information, whereas 29.1% (142/488) said that their needs were not met. Having unmet needs was related to greater levels of perceived stress (P=.005) and depressive symptomatology (P=.03). CONCLUSIONS: This study provides evidence for the important role of the internet in accessing infertility information and support and for the ability of Web-based resources to meet patients' needs. However, although distressed patients reported particularly high rates of searching, their needs were not always met, suggesting that they may benefit from alternative sources of information and support or guidance from health care providers when searching the internet.

Gene expression analysis of follicular cells revealed inflammation as a potential IVF failure cause.

PURPOSE: Hormonal stimulation prior to IVF influences the ovarian environment and therefore impacts oocytes and subsequent embryo quality. Not every patient has the same response to the same treatment and many fail for unknown reasons. Knowing why a cycle has failed and how the follicles were affected would allow clinicians to adapt the treatment accordingly and improve success rate. This study examines the hypothesis that transcriptomic analysis of follicular cells from failed IVF cycles reveals potential reasons for failure and provides new information on the physiological mechanisms related to IVF failure. METHODS: Follicular cells (granulosa cells) were obtained from IVF patients of four Canadian fertility clinics. Using microarray analysis, patients that did not become pregnant following the IVF cycle were compared to those that did. Functional analysis was performed using ingenuity pathway analysis and qRT-PCR was used to validate the microarray results in a larger cohort of patients. RESULTS: The microarray showed 165 differentially expressed genes (DEGs) in the negative group compared to the pregnancy group. DEGs include many pro-inflammatory cytokines and other factors related to inflammation, suggesting that this process might be altered when IVF fails. Overexpression of several factors, some of which act upstream from vascular endothelial growth factor (VEGF), also indicates increased permeability and vasodilation. Some DEGs were related to abnormal differentiation and increased apoptosis. CONCLUSIONS: Our results suggest that failure to conceive following IVF cycles could be associated with an imbalance between pro-inflammatory and anti-inflammatory mediators. The findings of this study identify potential failure causes and pathways for further investigation. Stimulatory protocols personalized according to patient response could improve the chances of later success.

Obesity and Reproduction.

OBJECTIVE: To provide a comprehensive review and evidence-based recommendations for the delivery of fertility care to women with obesity. OUTCOMES: The impact of obesity on fertility, fertility treatments, and both short and long-term maternal fetal outcomes was carefully considered. EVIDENCE: Published literature was reviewed through searches of MEDLINE and CINAHL using appropriate vocabulary and key words. Results included systematic reviews, clinical trials, observational studies, clinical practice guidelines, and expert opinions. VALUES: The Canadian Fertility & Andrology Society (CFAS) is a multidisciplinary, national non-profit society that serves as the voice of reproductive specialists, scientists, and allied health professionals working in the field of assisted reproduction in Canada. The evidence obtained for this guideline was reviewed and evaluated by the Clinical Practice Guideline (CPG) Committee of the CFAS under the leadership of the principal authors. BENEFITS, HARMS, AND COSTS: The implementation of these recommendations should assist clinicians and other health care providers in counselling and providing reproductive care to women with obesity. VALIDATION: This guideline and its recommendations have been reviewed and approved by the membership, the CPG Committee and the Board of Directors of the CFAS. SPONSORS: Canadian Fertility & Andrology Society. RECOMMENDATIONS: Twenty-one evidence based recommendations are provided. These recommendations specifically evaluate the impact of obesity on natural fertility, fertility treatments, and maternal-fetal outcomes. Strategies to lose weight and BMI cut-offs are also addressed.

No. 356-Egg Freezing for Age-Related Fertility Decline.

OBJECTIVE: To provide a comprehensive review and evidence based recommendations for Canadian fertility centres that offer social egg freezing. OUTCOMES: In social egg freezing cycles we evaluated thawed oocyte survival rates, fertilization rates, embryo quality, pregnancy rates, and live birth rates. We also review how these outcomes are impacted by age, ovarian reserve, and the number of eggs cryopreserved. Finally, we discuss the risks of social egg freezing, the alternatives, the critical elements for counselling and informed consent, and future reporting of egg freezing outcome data. EVIDENCE: Published literature was reviewed through searches of MEDLINE and CINAHL using appropriate vocabulary and using key words ("oocyte cryopreservation," "egg freezing," "egg vitrification," "social egg freezing," and "elective egg freezing"). Results included systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. Expert opinion based on clinical experience, descriptive studies, or reports of expert committees was also included to discuss aspects of egg freezing not currently rigorously studied. VALUES: The evidence obtained was reviewed and evaluated by the Clinical Practice Guideline (CPG) Committees of the Canadian Fertility and Andrology Society (CFAS) under the leadership of the principal authors. BENEFITS, HARMS, AND COSTS: Implementation of this guideline should assist the clinician to develop an optimal approach in providing counselling for egg freezing while minimizing harm and improving patient outcomes during treatment. VALIDATION: These guidelines have been reviewed and approved by the membership of the CFAS and by the CPG Committees of CFAS and The Society of Obstetricians and Gynaecologists of Canada (SOGC). SPONSORS: CFAS and SOGC.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3-4 and [Formula: see text] 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78-7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with [Formula: see text] 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.

PROBLEM: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year-outcomes and to develop a framework for IVIg use in RPL. METHOD OF THE STUDY: Retrospective, single-center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2 , non-smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6-0.8 g/kg was given prior to conception and monthly during pregnancy until 16-20 weeks' gestation. We compared IVIg treated patient's outcomes to a separate "natural history cohort". This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2-year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. RESULTS: Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15-10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub-group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. CONCLUSION: IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off-label use. We propose considering IVIg in well-selected patients with high order RPL who have failed standard medical therapy. Further mechanistic studies are needed to understand immune-mediated RPL and IVIg's mode of action. This will enable further refinement of treatment criteria and the development of standardized protocol for its use in RPL.

Optimal endometrial thickness in fresh and frozen-thaw in vitro fertilization cycles: an analysis of live birth rates from 96,000 autologous embryo transfers.

OBJECTIVE: To study the effect of increasing endometrial thickness on live birth rates in fresh and frozen-thaw embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: National data from Autologous in vitro fertilization (IVF) embryo transfer and FET cycles in Canada from the Canadian Assisted Reproductive Technology Registry Plus (CARTR Plus) database for records between January 2013 and December 2019. PATIENTS: Thirty-three Canadians clinics participated in voluntary reporting of IVF and pregnancy outcomes to the Canadian Assisted Reproductive Technology Registry Plus database, and a total of 43,383 fresh and 53,377 frozen transfers were included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy, pregnancy loss, and live birth rates. RESULTS: In fresh IVF-embryo transfer cycles, increasing endometrial thickness is associated with significant increases in the mean number of oocytes retrieved, peak estradiol levels, number of usable embryos, clinical pregnancy rates, live birth rates, and mean term singleton birth weights, and a decrease in pregnancy loss rates. However, live birth rates plateau after 10-12 mm. In contrast, in FET cycles live birth rates plateau after the endometrium measures 7-10 mm. The improvement in live birth rates with increasing endometrial thickness was independent of patient age, timing of embryo transfer (e.g., cleavage stage vs. blastocyst stage), or the number of oocytes at retrieval. CONCLUSIONS: In cycles with a fresh embryo transfer, live birth rates increase significantly until an endometrial thickness of 10-12 mm, while in FET cycles live birth rates plateau after 7-10 mm. However, an endometrial thickness <6 mm was associated clearly with a dramatic reduction in live birth rates in fresh and frozen embryo transfer cycles.

"Who needs an app? Fertility patients' use of a novel mobile health app".

Objective: The number of couples experiencing infertility treatment has increased, as has the number of women and men experiencing infertility treatment-related stress and anxiety. Therefore, there is a need to provide information and support to both men and women facing fertility concerns. To achieve this goal, we designed a mhealth app, Infotility, that provided men and women with tailored medical, psychosocial, lifestyle, and legal information. Methods: This study specifically examined how fertility factors (e.g. time in infertility treatment, parity), socio-demographic characteristics (e.g. gender, education, immigrant status), and mental health characteristics (e.g. stress, depression, anxiety, fertility-related quality of life) were related to male and female fertility patients' patterns of use of the Infotility app. Results: Overall, the lifestyle section of the app was the most highly used section by both men and women. In addition, women without children and highly educated women were more likely to use Infotility. No demographic, mental health or fertility characteristics were significantly associated with app use for men. Conclusion: This study shows the feasibility of a mhealth app to address the psychosocial and informational needs of fertility patients.

Predictors of infertility-related concerns in a Canadian survey of men and women seeking fertility treatment.

OBJECTIVE: To examine if and how factors associated with infertility-related concerns and opportunity to discuss concerns differ between male and female fertility patients. METHODS: A cross-sectional survey of 313 female and 254 male patients recruited from Canadian fertility clinics. An online survey asked about sociodemographic characteristics, psychological distress, the severity of psychosocial concerns on a scale of 0 (not concerned) to 5 (very concerned) related to fertility treatment, and their opportunity and desire to discuss concerns with healthcare providers (HCPs). RESULTS: For women, higher stress, educational attainment and being childless were associated with higher concern (F(6, 287) = 14.73, p < .001). For men, higher stress, being religious and longer treatment duration were associated with higher concern (F(8, 222) = 9.87, p < .001). No significant difference existed between men's and women's average concern scores (t(558) = -1.62, p = .11) or opportunity to discuss concerns (t(149) = 0.28, p = .78). CONCLUSION: Our results indicate an unmet need and desire for support among subgroups of patients who were concerned about psychosocial issues related to infertility, but did not have the opportunity to discuss these issues with HCPs. PRACTICE IMPLICATIONS: There is a need to tailor resources to address the concerns of male and female fertility patients from diverse sociodemographic backgrounds and with different fertility histories.

Impact of body mass index on IVF and ICSI outcome: a retrospective study.

A group of 140 women with a body mass index (BMI) < or = 24 kg/m(2) undergoing 291 cycles was compared with a group of 138 women with a BMI >24 kg/m(2) in 291 cycles, with respect to duration of ovarian stimulation and dose of gonadotrophin, number of oocytes collected, cleavage and implantation rate, clinical pregnancy, miscarriage and delivery rates. Patients with a BMI > 24 kg/m(2) demonstrated a significant decrease in the number of follicles after stimulation (P = 0.01), a comparative increase in the number ampoules of gonadotrophin used (P = 0.03) and a lower number of eggs collected (P = 0.05). The mean number of embryos on days 1, 2 and 3 was significantly lower in the group with BMI > 24 kg/m(2) (P < 0.001). No significant difference was found in clinical pregnancy and miscarriage rates between the two groups. In spite of the lower response in women with BMI > 24 kg/m(2), the delivery rate per retrieval was not different (24.6 versus 24.8%). These results indicate a lower stimulation response in women with elevated BMI, but no adverse effect on IVF outcome. In relation to wellbeing, however, it is recommended that patients with a high BMI reduce their weight before IVF treatment.

The familial risk of breast cancer in women with endometriosis from Yale series.

OBJECTIVE: Few studies examining the association of endometriosis with the risk of breast cancer. Our goal was to investigate the familial risk of breast cancer in women with endometriosis. DESIGN: Retrospective study. SETTING: University-based endometriosis referral center. PATIENTS: Three hundred fifty-two women with endometriosis and 180 infertile women without endometriosis were studied using laparoscopy between August 1996 and February 2002. The endometriosis group was further subdivided into a group of women with 94 positive and 268 negative family histories of breast cancer. MAIN OUTCOME MEASURE(S): The overall risk of familial breast cancer among first- and second-degree relatives in patients with endometriosis and the association between potential risk factors was estimated by chi(2) and by crude adjusted odds ratios (95% CI). RESULTS: Positive family history of breast cancer was detected in (26.7%) 94/352 of endometriosis group and in (5%) 9/180 of controls. The relative risk of women with endometriosis and positive family history of breast cancer was (OR=6.9 (95% CI, 3.4-14.1), chi(2)=34.6, P<0.001). Endometriosis was associated with the risk of first-degree relatives of breast cancer (OR=5.69 (95% CI, 2.4-13.3), P<0.001). Moreover, endometriosis was significantly associated with the risk of breast cancer in mothers (OR=6.3 (95% CI, 2.2-17.8), P<0.001) and in maternal aunts (OR=5.9 (95% CI, 1.3-72.9), P<0.001). The two groups are similar in age, race height, main complaints, age of menarche, cycle length, days of flow, estimated blood loss, stage of endometriosis and the presence of endometrioma. CONCLUSION(S): This study found an elevated risk associated with family history of breast cancer among women with endometriosis. A familial clustering interaction with a familial history of breast cancer in women with endometriosis is possible, but should be investigated further.

Familial aggregation of endometriosis in the Yale Series.

OBJECTIVE: To investigate the familial aggregation and the risk of endometriosis among the female relatives of women with endometriosis. We also compared the epidemiologic characteristics of women with and without family history of endometriosis. PATIENT(S): A total of 485 women with endometriosis and 197 infertile women without endometriosis underwent surgical investigation between August 1996 and February 2002. MAIN OUTCOME MEASURE(S): The relative risk of endometriosis in a first-degree relative and the association between potential risk factors was estimated by chi2 and by crude adjusted odds ratios (95% CI). RESULTS: Endometriosis was identified in 9.5% of first-degree relatives of women with endometriosis versus only 1% of controls. The odds ratio for endometriosis in a first-degree relative was 10.21 (95% CI 2.45-42.5; P<0.001). In 3.9% of cases women with endometriosis reported that their mother had been diagnosed with endometriosis and 5.6% of cases that at least one sister had been diagnosed. Compared to the control group the odds ratio for the mother having endometriosis (7.99, 95% CI 1.06-60.1) or at least one sister having (11.55, 95% CI 1.56-85.59) were significantly elevated. Among women with endometriosis who reported a family history of endometriosis, and women with endometriosis who did not report a family history of endometriosis, there were no differences in demographic characteristics, body habitus, or menstrual parameters. CONCLUSION(S): Women with endometriosis have a tenfold increased risk of endometriosis in their first-degree relatives.

A Comparison of Immigrant and Canadian-Born Patients Seeking Fertility Treatment.

The present study examined whether public funding for in vitro fertilization (IVF) in Quebec, Canada was associated with differential access among Canadian-born infertility patients and those born outside of Canada. Anonymous demographic questionnaires were completed at 3 time points: 2 weeks before the implementation of public funding, 2 weeks after, and 8 months later. Almost half the patients were not born in Canada and of these, 35 % were recent immigrants to Canada. While patients born outside Canada were generally better educated than Canadian-born patients, they were more likely to be unemployed and have lower incomes. Following public funding, there was an overall increase in patients with lower incomes and lower levels of education. Canadian-born patients were more likely than immigrant patients to consult for secondary infertility. Patients born outside Canada tended to be older and nulliparous, suggesting that they may have delayed treatment seeking due to financial and other barriers. The results indicate that public funding reduces health disparities in access to IVF.

New advances in the understanding of endometriosis related infertility.

The association between endometriosis and infertility is complex. Nevertheless, in the absence of tubal distortion considerable evidence suggests four principle factors likely to contribute to subfertility. These include impaired folliculogenesis, decreased fertilization, inflammatory factors in follicular, peritoneal and reproductive tract fluid, and implantation defects. The potential impact of each of these is critically examined. The role of endometriomas, prior surgeries and donor oocytes is also discussed.

Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis.

OBJECTIVE: Peritoneal fluid (PF) inflammatory factors may participate in the pathogenesis of endometriosis. The aim of this study was to investigate PF interleukin (IL)-18 levels in women with and without endometriosis. DESIGN: Controlled clinical study. SETTING: Women undergoing laparoscopy at a university hospital. PATIENT(S): Fifty women with previously untreated endometriosis, 8 women on GnRH agonists for endometriosis, and 18 control women with normal pelvic anatomy who were undergoing tubal ligation. INTERVENTION(S): Peritoneal fluid IL-18 levels as measured by ELISA. MAIN OUTCOME MEASURE(S): Peritoneal fluid IL-18 levels. RESULT(S): Peritoneal fluid IL-18 levels were significantly higher in women with previously untreated endometriosis (mean +/- SEM, 91.1 +/- 6.5 pg/mL) than in control women (59.4 +/- 2.0 pg/mL). Interestingly, women with superficial (100.0 +/- 10.2 pg/mL) and deep peritoneal implants (94.0 +/- 10.8 pg/mL) had significantly higher PF IL-18 levels than did women with endometriomas (57.8 +/- 1.8 pg/mL). Similarly, women with stage I-II endometriosis (97.3 +/- 8.0 pg/mL), but not women with stage III-IV endometriosis (74.9 +/- 9.9 pg/mL), had significantly higher PF IL-18 levels than did control women. Peritoneal fluid IL-18 levels were significantly higher in the luteal phase than in the follicular phase but did not discriminate between women with pelvic pain or infertility. CONCLUSION(S): Peritoneal fluid IL-18 is elevated in women with peritoneal, minimal- to mild-stage endometriosis.

Elevations in peritoneal fluid macrophage migration inhibitory factor are independent of the depth of invasion or stage of endometriosis.

OBJECTIVE: To quantify levels of macrophage migration inhibitory factor (MIF) in the peritoneal fluid (PF) of women with endometriosis, and to correlate these levels with the extent of disease. DESIGN: Controlled clinical study. SETTING: Academic medical center. PATIENT(S): Peritoneal fluid samples were collected during laparoscopic surgery in 60 women with endometriosis and 16 controls undergoing tubal ligation; 52 of the women with endometriosis had received no hormonal treatment in the 6 months prior to surgery, while 8 were using gonadotropin-releasing hormone (GnRH) agonists. MAIN OUTCOME MEASURE(S): Peritoneal fluid migration inhibitory factor (PF MIF) levels. RESULT(S): Women with endometriosis had significantly higher PF MIF levels (10.8 +/- 0.9 ng/mL) than controls (3.0 +/- 0.7 ng/mL). However, no correlation existed between MIF levels and the stage of disease (r = 0.05) or the depth of endometriotic invasion (r = 0.08). Moreover, treatment with a GnRH agonist did not suppress PF MIF levels. Peritoneal fluid MIF levels did not vary significantly between the proliferative and secretory phases of the cycle, and did not distinguish women with endometriosis-associated infertility from women with endometriosis-associated pain. CONCLUSION(S): Peritoneal fluid migration inhibitory factor levels are markedly elevated in women with endometriosis but are independent of the extent of disease.

Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study.

OBJECTIVE: To investigate whether conservative surgery on ovarian endometriomas before an IVF cycle improves fertility outcomes. DESIGN: Retrospective, matched case-control study. SETTING: Two academic IVF programs. PATIENT(S): One hundred eighty-nine women with endometriomas who underwent IVF treatment: 56 women proceeded directly to IVF, and 133 first underwent conservative ovarian surgery. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF-ET. MAIN OUTCOME MEASURE(S): Response to gonadotropins, fertilization, implantation, and pregnancy rates. RESULT(S): Aside from lower peak E(2) levels on the day of hCG and a higher total FSH dose in women previously operated for an endometrioma, no significant differences were found between the two groups in the different IVF variables analyzed. CONCLUSION(S): Laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes. Proceeding directly to controlled ovarian hyperstimulation in women with asymptomatic ovarian endometriomas might reduce the time to pregnancy, the costs of treatment, and the hypothetical complications of laparoscopic surgery. Conversely, conservative surgical treatment of ovarian endometriomas in symptomatic women does not impair IVF or intracytoplasmic sperm injection success rates.