N-glycans from serum IgG and total serum glycoproteins specific for endometriosis.

Endometriosis is a chronic inflammatory gynaecological disease characterized by the growth of endometrial tissue outside the uterine cavity. There are currently no definitive non-invasive diagnostic tools. Glycosylation is the most common posttranslational modification of proteins and altered glycosylation has been found in many diseases, including chronic inflammatory conditions and cancer. Sialylation and galactosylation on serum IgG have previously been found to be altered in endometriosis and serum sialylation changed after Zoladex (Goserelin Acetate) therapy. Using IgG and whole serum glycoproteins, we investigated N-glycosylation in two clinical cohorts of women with and without endometriosis. PNGase F-digested serum samples were fluorescently labelled and N-glycans were profiled by ultra-performance liquid chromatography. Clinical data was collected to link glycomic findings with metabolic and hormonal profiles. Total serum glycoprotein and IgG glycosylation differed in patients with endometriosis compared to control cases. The most significantly altered was glycan peak 3 from IgG, containing bisected biantennary glycans, which was decreased in the endometriosis cohorts (p = 0.0000005-0.018). In conclusion, this is the first pilot study to identify changes in N-glycans from whole serum glycoproteins associated with endometriosis. A larger validation study is now warranted and such studies should include the follow-up of surgically and pharmacologically treated patients.

Irish fertility patients' attitudes to pregnancy and risk mitigation strategies during the COVID-19 pandemic.

The effects of COVID-19 on fertility services became evident in early 2020. Fertility treatments were initially suspended following advice from international fertility governing bodies. We performed a web-based study to investigate the attitudes of male and female fertility patients in Ireland, for risk mitigation strategies and pregnancy advice during the first wave of COVID-19. Despite international recommendations and uncertainty regarding COVID-19 and pregnancy, over two thirds of patients continued trying to conceive, while awaiting recommencement of fertility services. When services resumed, the majority were keen to continue fertility treatment. They were agreeable to telemedicine in place of face-to-face consultations. They felt that privacy was maintained and were comfortable signing consent forms via video link. Large numbers, however, strongly disagreed with the no-partner policy for embryo transfer and early pregnancy scanning, highlighting the importance of partner support. Patients felt strongly that fertility treatments should be classified as essential services and that every effort should be made to continue treatments in future pandemics. These results highlight the importance of maintaining fertility services, while adapting to new practices that may be required. The primary concern of the infertility population is the desire for pregnancy and parenthood. This innate human need trumps concerns regarding COVID-19 for the majority of those affected.

Mid-luteal uterine artery Doppler indices in the prediction of pregnancy outcome in nulliparous women undergoing assisted reproduction.

Traditionally, the assessment of endometrial receptivity at transvaginal ultrasound scan has been based on the thickness and the morphological appearance of the endometrium. The objective of this study was to prospectively evaluate endometrial thickness (ET), endometrial morphology and uterine artery Doppler parameters prior to assisted reproduction treatment (ART) in the prediction of pregnancy outcome. This was a prospective cohort study. ET, morphology and uterine artery Doppler (UtAD) pulsatility index (PI) and resistance index (RI) were measured in the mid-luteal stage of the menstrual cycle ultrasonographically, timed with urinary luteinizing hormone testing. A total of 50 women were included in the analysis. The clinical pregnancy rate (CPR) per embryo transfer was 42.0% (n = 21/50). Twenty nine women (58.0%) had an unsuccessful outcome. There were no differences in mean ± SD endometrial thickness (ET) (10.0 ± 1.8 mm vs. 10.5 ± 2.4; p = 0.43), or endometrial morphology (100% (n = 21) vs 100% (n = 29); p = 1.00) between the pregnant and not pregnant groups. Similarly, there were no differences in mean ± SD UtAD PI (2.17 ± 0.83 vs. 2.07 ± 0.81; p = 0.67 or mean ± SD UtAD RI (0.84 ± 0.10 vs. 0.81 ± 0.10; p = 0.30). Ultrasonographic endometrial assessment did not differentiate between those who would have a subsequent clinical pregnancy.

Managing endometrioma to optimize future fertility.

The management of endometriomas in women wishing to preserve their fertility is complex. While surgery can help to achieve pregnancy in some, it may also have a detrimental effect on a woman's ovarian reserve. The present article reviews the impact of endometriomas on fertility and the different management approaches that should be considered in women who wish to preserve their fertility. This study also reviews the role of assisted reproduction in the setting of endometriomas, and the evolving role of oocyte cryopreservation for this benign but progressive disease. Using evidence from the latest guidelines and major publications, we emphasize the need to consider the woman's future fertility when navigating the diverse range of management strategies available, and outline an evidence-based framework to help facilitate fertility-friendly discussion, counseling and management of this complex disease.

COVID-19 vaccine - can it affect fertility?

Headlines have appeared across multiple social media platforms questioning the effects of newly authorised COVID-19 vaccines on fertility. Although the effects on future fertility were not studied in the initial trials, at present, there is no evidence that the COVID-19 vaccine has any effect of future fertility. It is well known that pregnant women are at a higher risk of complications associated with COVID-19 such as ICU admission and death, and there is a rare but tragic increase in placentitis and stillbirth, highlighting the importance for those planning a pregnancy any time in the future to be vaccinated. Here we summarise international consensus from multiple organisations advising on fertility and the COVID-19 vaccine. Preliminary studies all suggest that there is neither link, nor indeed any theoretical reason why any of the COVID-19 vaccines might affect fertility. Dissemination of misinformation regarding the impact of the vaccine on future fertility needs to be controlled in order to avoid any hesitancy amongst young women attending for vaccination. It is also vital that the medical profession counteract this information, and, in order to do that, healthcare providers must be well informed on the latest recommendations and research.

The impact of accurately timed mid-luteal endometrial injury in nulligravid women undergoing their first or second embryo transfer.

INTRODUCTION: Endometrial injury or 'scratch' preceding an assisted reproductive therapy (ART) cycle has recently been shown not to improve livebirth rates among women undergoing ART. The objective of this study was to compare pregnancy outcomes in nulliparous women who underwent an accurately timed mid-luteal scratch biopsy prior to ART with those who did not. METHODS: This was a prospective cohort study. Women were recruited between October 2016 and February 2018 inclusive. Women who met the inclusion criteria and who did not undergo an endometrial scratch in the study period were used as a comparison group. Patients underwent a cycle of ART in the menstrual cycle following endometrial scratch. RESULTS: Ninety-eight women were eligible for participation in the study. There were no differences in rates of implantation (35.7% (n = 20/56) vs. 35.4% (n = 17/48); p = 1.00), clinical pregnancy (40.0% (n = 20/50) vs. 39.5% (n = 17/43); p = 1.00) or live birth (34.0% (n = 17/50) vs. 25.6% (n = 11/43); p = 0.50) per embryo transfer between those who underwent a scratch and those who did not. CONCLUSION: Endometrial scratch is a simple, inexpensive and low-risk procedure. However, in this relatively small cohort study, no differences in rates of implantation, clinical pregnancy or live birth in women with primary infertility were determined between those who underwent a scratch and those who did not.

"So what happens next?" exploring the psychological and emotional impact of anti-Mullerian hormone testing.

Research Question: Significant medical benefits could be derived from universal AMH screening for women in their mid to late twenties. We aimed to investigate the psychological and emotional responses of women to being informed of their anti-Mullerian hormone (AMH) result with a view to informing the possible introduction of universal AMH screening.Materials and methods: This was a prospective qualitative study using semi-structured in-depth interviews of women attending a reproductive medicine clinic who had ovarian reserve testing performed via measurement of serum AMH levels, as part of their gynecological investigations. A semistructured interview schedule was developed after a review of the literature. A purposive sample of women was recruited, and data collection continued until thematic saturation was reached (n = 10). The number of women interviewed is low as this was a pilot qualitative study of a two-part study. The next part of the study involves the development of a quantitative questionnaire related to the key themes identified in this study to be based on a much larger group of women. Interviews were audiotaped, transcribed verbatim and imported into QSR NVivo pro 11 for analysis.Results: Three key themes emerged from the data: the experience of AMH testing, the response to the AMH result, and suggested lessons for medical professionals. The theme of the experience of AMH testing describes and reflects two sub-themes: the reasons for ovarian reserve testing and the potential barriers that may prevent women from accessing testing. A further key focus of this study was the emotional and psychological responses to receiving an AMH result and this emerged as a major theme in the interviews. Women described the significant impact that their individual result had on a number of lifestyle and behavioral factors and how it impacted on their gender identity. Lessons for medical professionals including the appreciation of the patient's awareness of the test and how the test result was relayed to the patient were important factors in how they dealt with the result. There were mixed reactions and opinions from the group in relation to the introduction of AMH testing as a screening tool for all young women.Conclusions: Knowledge and communication of a low AMH result has a negative psychological impact. The findings from this study support the move to further explore the psychological and emotional impact of the test with the development of a quantitative questionnaire.

Influence of body mass index on the relationship between endometrial thickness and pregnancy outcome in single blastocyst frozen embryo transfer cycles.

To date there is limited published data assessing whether body mass index (BMI) influences endometrial thickness (ET) and whether this impacts on pregnancy outcomes in single blastocyst FET cycles. The objective of this study, therefore, was to examine the relationship between BMI and ET on the outcome of single blastocyst FET cycles over a five-year period from 2012 until 2016. Patient age, BMI, endometrial pattern and ET prior to FET were recorded. Pregnancy outcomes included: implantation rate, clinical pregnancy rate and live birth rate. A total of 464 cycles met the inclusion criteria and the female age was 36.0 ± 3.0 years (mean ± SD). The mean ± SD BMI was 23.3 ± 3.1 kg/m2 and median ± SD ET was 8.1 ± 1.5 mm. BMI and ET were modestly correlated (Pearson r = 0.244) and there was an association between higher BMI category and higher median ET (7.2, 8.0, 8.3, 8.9 mm; p < 0.001). However, there was no association between ET and pregnancy outcome, either unadjusted, or adjusted for BMI, age, endometrial pattern or embryo quality. The data suggests that although ET increases with increasing BMI, there are no differences in cycle outcome. Importantly, this implies that an ET <8 mm may not jeopardize pregnancy outcome in women with lower BMI. The development of a norm referenced test for BMI and ET may prove to be a helpful adjunct in the clinical IVF setting.

Anti-Müllerian hormone and progesterone levels in human follicular fluid are predictors of embryonic development.

BACKGROUND: Human follicular fluid is an intricate biological fluid contributing to the developing oocyte microenvironment. Accumulating evidence suggests that sex hormones present in follicular fluid (FF) may play an important role in regulating oocyte developmental potential. The aim of this study was to determine if anti-Müllerian hormone (AMH) and progesterone (P4) levels in FF are correlated with oocyte quality as defined by subsequent embryonic development. METHODS: This was a prospective cohort study of 88 women undergoing IVF/ICSI at a university associated fertility clinic. Follicular fluid was collected from the first follicle aspirated at the time of oocyte retrieval. The corresponding oocyte was individually cultured in order to track its developmental outcome. FF-AMH and P4 concentrations from follicles where the oocyte fertilised normally and developed into a blastocyst on day 5 (Group 1: BLAST, n = 23) were compared with FF from follicles where the oocyte fertilised normally but failed to reach blastocyst stage by day 5 (Group 2: FERT, n = 19). No significant differences were observed between the two groups in terms of maternal age, body mass index, previous live births, previous pregnancy loss, number of antral follicles, number of oocytes recovered, IVF:ICSI ratio or percentage of recovered oocytes that fertilised. RESULTS: FF-AMH and P4 levels were significantly increased in Group 1: BLAST compared to Group 2: FERT (P = 0.007 and P = 0.013 respectively). Twenty-one FF samples had an AMH level > 15 pmol/L, of which 17 related to oocytes that progressed to blastocyst stage, providing a positive prediction value (PPV) of 76.96%. Eleven FF samples had a P4 level > 60 mg/ml, of which 10 progressed to blastocyst stage, providing a PPV of 90.99%. Six samples had an AMH level > 15 pmol/L and a P4 level > 60 mg/ml, of which 100% progressed to blastocyst stage, providing a PPV of 96.83%. CONCLUSIONS: FF-AMH and P4 levels from individual follicles can accurately predetermine subsequent embryonic development. Combining follicular fluid analysis with routine morphological assessment, could allow for a more accurate and sensitive method of determining embryonic developmental competence.

Reproductive ageing-turning back the clock?

BACKGROUND: Unintended childlessness is a distressing, and often unintended, consequence of delayed childbearing and reproductive ageing. The average maternal age at first birth has risen steadily in many industrialised countries since the 1980s. There are many societal factors involved in the decision to postpone motherhood. As a result, many women are postponing having children until it is too late. In this review, we aim to summarise the reasons behind delayed childbearing, the impact of delayed childbearing and the scientific advances that seek to reverse reproductive ageing and ensure reproductive autonomy for women. METHODS: An extensive literature search of PubMed was conducted to include all published articles on delayed childbearing and the consequences of reproductive ageing. Secondary articles were identified from key paper reference listings. CONCLUSION: If the current reproductive trends continue, many women will find themselves in the harrowing position of being unintentionally childless. In addition, many will inevitably turn to assisted reproductive technologies in an effort to protect and preserve their reproductive autonomy. However, it is not always possible to reverse the effects of reproductive ageing.

Expression of granulosa cell microRNAs, AVEN and ATRX are associated with human blastocyst development.

A greater understanding of the key molecules associated with embryo development during human-assisted reproduction is imperative for the development of advanced diagnostics. Previous studies have shown that follicular microRNAs (miRNAs) are reliable markers of the polycystic ovarian syndrome (PCOS). Leveraging the utility of miRNAs in PCOS, the aim of this study was to identify miRNAs in human granulosa cells that may be indicative of blastocyst development. Granulosa cells and oocytes were collected from the first follicle aspirated from patients undergoing oocyte retrieval for in vitro fertilization or intracytoplasmic sperm injection. The development of isolated oocytes was recorded, and granulosa cell samples in this study were separated as follows. Group 1-BLAST: granulosa cells from follicles containing an oocyte that fertilized and developed into a blastocyst, and Group 2-FERT: granulosa cells from oocytes that fertilized but failed to reach blastocyst. A panel of 84 miRNAs, related to development and cellular differentiation, was assessed between the two groups using a miScript PCR array. Fourteen miRNAs and one snoRNA were differentially expressed between the groups. In addition, two downstream candidate protein biomarkers, ATRX and AVEN, were also found to be differentially expressed between the groups. The findings of this pilot study reveal follicular abnormalities on a molecular level, which may affect oocyte competence and its potential to develop successfully as an embryo. We encourage additional studies to confirm and expand on our findings and to determine the usefulness of granulosa-borne miRNAs, ATRX, and AVEN as biomarkers.

Uterine natural killer cell progenitor populations predict successful implantation in women with endometriosis-associated infertility.

PROBLEM: Uterine natural killer (uNK) cells play a critical role early in gestation. As we previously identified altered uNK cell development in endometriosis-associated infertility, we herein sought to characterize natural killer (NK) cell profiles in endometriosis that may predict embryo implantation. METHOD OF STUDY: Study participants had a surgical diagnosis of endometriosis-associated infertility. Endometrial tissue and peripheral blood were obtained from 58 women. Thirty-three patients underwent artificial reproductive technology (IVF, ICSI, or IUI) within a mean of 9.5 months of surgery. NK and hematopoietic progenitor cells from endometrium and blood were analyzed by flow cytometry. Successful implantation was defined as a positive pregnancy test. RESULTS: In successful implantation, populations of endometrial CD34+ hematopoietic stem cells were higher (3.97% vs 0.69%; P < .0004), and coexpression of NK cell marker CD56 was increased (81.1% vs 60.9%; P < .034) compared with patients who had failed implantation. In contrast, levels of blood NK progenitors were similar in both groups. CONCLUSION: Our study revealed that uterine NK progenitor cell populations are markedly different in patients with endometriosis who proceed to successful or failed embryo implantation and may define a novel predictor of implantation success. Our findings also highlight the fundamental differences inherent in NK cell repertoires between blood and uterine compartments.

What women want? A scoping survey on women's knowledge, attitudes and behaviours towards ovarian reserve testing and egg freezing.

OBJECTIVE: We aimed to investigate women's knowledge, attitudes and behaviours towards ovarian reserve testing and egg freezing for non-medical reasons in the general population. STUDY DESIGN: This was a cross-sectional survey study of 663 women aged 18-44 years which assessed female perception of ovarian reserve testing and oocyte cryopreservation. An online forum was used to deliver the survey through the use of two social media sites. Participants were recruited through the technique of "snowballing", whereby existing study subjects recruited others from among their acquaintances. The data collected was analyzed using SPSS to explore descriptive statistics and frequencies relating to the participants' knowledge, attitudes and behaviour towards the practices of ovarian reserve testing and oocyte cryopreservation. Categorical variables were analyzed using Chi-squared; a p-value of <0.05 was considered significant. RESULTS: A majority (60%) of women surveyed had knowledge of ovarian reserve testing. 64.8% would be interested in having testing performed. Younger women (<30 years of age) were more interested in checking their ovarian reserve (75.8% vs. 59.1%, p<0.0001). Single women were also more likely to be interested, (73.6% v's 62.1%, p=0.022). 89.7% of women surveyed were aware of oocyte cryopreservation. 72.2% agreed that they would consider freezing their eggs to preserve fertility. There was no significant difference in the numbers of single women compared to women in a relationship who would consider egg freezing to preserve fertility (75.7% v's 71.2%, p=0.347, or in younger (<30years) compared to older women, (74.7% v's 71.1%, p=0.387). A majority (62.1%) of study participants believed that it is a woman's right to postpone pregnancy for social reasons and to freeze her eggs, with no significant difference in options noted between younger and older women. CONCLUSIONS: Knowledge of ovarian reserve testing and oocyte cryopreservation for non-medical reasons were higher than in previous studies, possibly reflecting increasing awareness of these issues among the general public. Additionally, we demonstrated that the women, in our study, were very open to the use of these modern technologies in an attempt to avoid unintended childlessness.

Review of clinical indicators, including serum anti-Müllerian hormone levels, for identification of women who should consider egg freezing.

OBJECTIVE: To identify women, on the basis of clinical history and serum anti-Müllerian hormone (AMH) levels, who are at risk of premature ovarian insufficiency and thereby guide appropriate early referral for egg freezing. METHODS: In a retrospective study, data were reviewed from women attending two fertility clinics in Dublin, Ireland, between August 2011 and December 2012. Case histories of women aged 35 years or younger were assessed to identify risk factors for reduced ovarian reserve, including endometriosis, ovarian surgery, and family history of premature ovarian failure (POF). RESULTS: Among 490 women aged 35 years or younger, 195 (39.7%) had an AMH level below 10 pmol/L, 94 (19.2%) had an AMH below 5 pmol/L, and 21 (4.3%) had an AMH below 1 pmol/L. Among 104 women aged 30 years or younger, the respective numbers were 28 (26.9%), 15 (14.4%), and 9 (8.7%). Among the 490 women, significantly lower AMH levels were observed for those with endometriosis (P=0.017) and a family history of POF (P=0.006). However, 53 (56.4%) of 94 women aged 35 years or younger with low AMH levels had no clinical risk factors. CONCLUSION: Universal AMH screening should be considered for all women in their 30s who are not ready to try to conceive; clinical risk factors will only identify approximately 50% of women at risk of low ovarian reserve.

A retrospective study of the effect of increasing age on success rates of assisted reproductive technology.

OBJECTIVE: To demonstrate the effect of increasing age on the outcome of assisted reproductive technology, particularly among women aged 40 years or older. METHODS: A retrospective analysis was conducted using prospectively collected data for all in vitro fertilization and intracytoplasmic sperm injection cycles among women aged 30-35 years or 40-44 years conducted at Merrion Fertility Clinic, Dublin, Ireland, between January 1, 2010, and December 31, 2014. The relationship between age and treatment outcome was assessed. RESULTS: Among women aged 30-35 years, 726 cycles led to 281 (38.7%) clinical pregnancies and 242 (33.3%) live births. By contrast, among women aged 40-44 years, 433 cycles led to 102 (23.6%) clinical pregnancies and 64 (14.8%) live births (both P<0.001). The live birth rate was particularly low after cycles among the women aged 42 years (5/89 [5.6%]) or 43 years (2/30 [6.7%]). CONCLUSION: The success rates of assisted reproductive technology are decreased among women aged older than 40 years. Fertility clinics have a responsibility to fully inform this group about the limitations of assisted reproductive technology.

Inflammatory Bowel Disease: Influence and Implications in Reproduction.

The incidence and prevalence of inflammatory bowel disease (IBD) continues to rise with time, signifying its emergence as a global disease. Clinical onset of IBD, comprising Crohn's disease and ulcerative colitis, typically occurs before or at peak reproductive age. Although active disease in female patients is associated with reduced fertility and adverse obstetric outcomes in pregnancy, the molecular mechanisms underlying this altered reproductive course, and its impact on IBD transmission to offspring, remain poorly understood. Clinical and experimental studies have now begun to elucidate the hormonal, environmental, and microbial factors that modulate immune-reproductive cross talk in IBD and define their impact on maternal health, fetal development, and heritability of disease risk. Evolving insight into maternal-fetal imprinting in IBD has important implications for patient counseling and disease management during pregnancy and may help predict clinical outcomes for both mother and child.

Vitamin D status and fertility outcomes during winter among couples undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To assess the vitamin D status of men and women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and to investigate associations between vitamin D status and fertility variables. METHODS: A cross-sectional prospective study was undertaken of men and women attending a fertility clinic in Ireland for IVF/ICSI between January and March 2014. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25(OH)D). Questionnaires examined knowledge and practices concerning vitamin D. Fertility variables and pregnancy outcomes were assessed in relation to vitamin D status. RESULTS: Overall, 73 men and 64 women provided blood samples. Among men, no correlation was found between 25(OH)D and total motility (ρ=0.069, P=0.562), progressive motility (ρ=0.066, P=0.576), count (ρ=0.001, P=0.996), or morphology (ρ=-0.034, P=0.774) of sperm. Additionally, there was no association between 25(OH)D and ongoing pregnancy rates (P=0.158). There was no difference in 25(OH)D between men with and without male factor subfertility issues (P=0.856). Among women, there was no significant correlation between 25(OH)D and anti-Müllerian hormone (P=0.629) or number of collected (P=0.198) and fertilized oocytes (P=0.136). There was no difference in 25(OH)D between women with and without ongoing pregnancy (P=0.222). CONCLUSION: No correlation was found between fertility variables or pregnancy outcomes and male or female vitamin D status.

Increased uNK Progenitor Cells in Women With Endometriosis and Infertility are Associated With Low Levels of Endometrial Stem Cell Factor.

PROBLEM: Uterine natural killer (uNK) cells play a significant role in successful human pregnancy. Having previously demonstrated uNK cell progenitors in human endometrium, we hypothesized that abnormal uNK cell maturation contributes to infertility in women with endometriosis. We aimed to characterize uNK cells at different developmental stages in women with and without endometriosis and to investigate possible mechanisms to explain any differences. METHOD OF STUDY: We characterized uNK cell development in women with and without endometriosis using flow cytometry, protein array and in vitro experiments. RESULTS: We found increased proportions of uNK cells at developmental stages 1 and 2 in endometrium from women with endometriosis (n = 36; mean = 21.2%) when compared with healthy fertile women (n = 9; mean = 7.0%). Protein array analysis revealed significantly lower levels of stem cell factor (SCF) in the eutopic endometrium of women with endometriosis when compared to healthy women. Addition of SCF to endometrial progenitor cells in vitro restored uNK cell maturation. CONCLUSION: We have shown that women with endometriosis have low levels of endometrial SCF, which we hypothesize contributes to abnormal maturation of local uNK cell populations. This defect may also compromise embryo implantation and hence contribute to endometriosis-associated infertility. SCF replacement may be a new therapeutic approach.

Natural Killer Cells: Key Players in Endometriosis.

Endometriosis affects more than 10% of women, causing significant pain and morbidity. It is also a significant cause of infertility. The aetiology of the disease remains an enigma, and the mechanisms responsible for the associated infertility are unclear. A role for immune cells in endometriosis has been postulated, with attention directed towards natural killer (NK) cells and macrophages. NK cells kill tumours and infected cells but also have roles in tissue remodelling in several organs including the uterus and are key to successful pregnancy. Here, we explore evidence (from peer-reviewed published articles) of phenotypic and functional abnormalities in NK cell subpopulations of women with endometriosis. It is clear that peripheral blood NK cells and peritoneal NK cells have reduced cytotoxic function in women with endometriosis. Uterine NK cells have a vital role in infertility, but very little research has been carried out in this area. We propose that abnormal u NK cell activity may contribute to the pathogenesis of endometriosis and its associated infertility and that future research should focus on this complex area.

Excisional treatments of the cervix and effect on subsequent fertility: a retrospective cohort study.

OBJECTIVE: Concerns exist regarding the impact of excisional treatments for cervical intraepithelial neoplasia (CIN) on subsequent pregnancy outcome yet few studies have addressed fertility following surgery. STUDY DESIGN: Retrospective cohort study. Set in the colposcopy service of National Maternity Hospital. A postal questionnaire was sent to 3590 women of reproductive age who attended colposcopy from 2001 to 2007; 1795 of these had at least one excisional treatment (surgical group) and 1795 had no treatment (non-surgical group). Records were reviewed to confirm the clinical details and volume of tissue excised. The main outcome measures were pregnancy and fertility rates as well as time to conception correlated with volume of tissue excised. Students' t-test, Mann-Whitney U-test, spearman correlation and Kruskal-Wallis tests were used during the analysis. RESULTS: 1355 Women (37.7%) responded. 537 Women had no treatment and 818 had at least one excision. A subsequent pregnancy was reported in 730 women (434 surgical and 296 non-surgical groups). No difference was detected between the groups in the reported pregnancy rates (p=0.56), the time to conception (p=0.37) or fertility problems (p=0.89). The volume of the excision did not affect fertility rates or time to conception. There were fewer pregnancies in women following a cold knife cone or more than one LLETZ treatment-significant surgery, (p=0.004) but no difference in their reported time to conception (p=0.54). CONCLUSIONS: One excisional treatment for CIN does not appear to affect subsequent fertility. Our study showed no delay in conception and no increased risk of problems conceiving in this group, even when controlling for the volume and depth of tissue removed. Women should be reassured by these results. Further work is required to evaluate the effect of cold knife cone biopsy and repeated LLETZ procedures on subsequent fertility.