The correlation between raised body mass index and assisted reproductive treatment outcomes: a systematic review and meta-analysis of the evidence.

BACKGROUND: Public funding for fertility services within the United Kingdom is limited, and therefore, strict guidance exists regarding who can be offered treatment under the National Health Service (NHS). Body mass index (BMI) is a universal criteria adopted by both the public and private sector. This study addresses an important aspect of the impact of a raised BMI on fertility treatment outcomes. We standardise the analysis of the data by only including studies incorporating the WHO BMI criteria; the current reference point for clinicians and clinical commissioning groups in ascertaining which group of patients should receive treatment. This study is an update of the previous systematic review performed in 2010, with the inclusion of a larger number of cycles from central databases such as the Society for Assisted Reproductive Technology (SART). METHODS: An electronic literature search was conducted through the Cochrane, Medline and Embase libraries. Data extraction for each outcome measure was pooled and expressed as an odds ratio with 95% confidence intervals. Where clinical heterogeneity was evident, the random effects model was used to calculate the risk ratio and a fixed effects model was used for the remaining studies. A p value < 0.05 was considered statistically significant. RESULTS: A total of 49 studies have been identified and included in this systematic review. Overweight and obese (BMI ≥ 25 kg/m2) women have a statistically significant lower live birth rate (OR 0.81, 95% CI 0.74-0.89, p < 0.00001) following Assisted Reproductive Technology (ART) when comparisons are drawn to women with a normal BMI. An increase is also demonstrated in the number of miscarriages experienced by women with a BMI ≥ 30 kg/m2 (OR 1.52, 95% CI 1.28-1.81, p < 0.00001). CONCLUSION: Although this review concludes that a clear impact of BMI on ART outcomes is demonstrated, there remains questions as to the pathophysiology underlying these differences. This review supports the government's stringent criteria regarding BMI categories under which NHS funding is made available for ART, through a clear description of poor reproductive outcomes in women with a BMI ≥ 30 kg/m2.

Grade of the inner cell mass, but not trophectoderm, predicts live birth in fresh blastocyst single transfers.

Debate continues over which morphological parameter is most important in selecting blastocysts for transfer. We aimed to investigate which parameter more accurately predicts the occurrence of a live birth by designing a retrospective cohort study of 1084 fresh elective single blastocyst transfers. Primary outcome was live birth rate (LBR) and secondary outcomes were implantation, clinical pregnancy and early pregnancy loss rates. Blastocyst expansion and inner cell mass (ICM), but not trophoectoderm, were associated with LBR in the definitive multivariable regression analysis. When ICM grade dropped from A to C the likelihood of achieving a live birth was reduced by 55% (OR= 0.45, 95% CI 0.26-0.79, p = .005). These results were similar for clinical pregnancy rates. Early pregnancy loss rates of embryos with ICM grade C were more than double (38.0%) compared to those of grades A (15.95%) and B (17.17%, p = .002). The transfer of an embryo with an optimal inner cell mass reduces early pregnancy loss and increases the likelihood of a live birth. We did not find any significant association between trophectoderm and LBR in the multivariable analysis in contrast with recent studies.

Randomized, controlled pilot trial of natural versus hormone replacement therapy cycles in frozen embryo replacement in vitro fertilization.

OBJECTIVE: To determine whether there is any difference between the outcomes of two standard treatment protocols for frozen embryo replacement (FER): natural and down-regulated hormone replacement treatment (HRT). DESIGN: Open, single-center, randomized, controlled pilot trial. SETTING: Private fertility clinic. PATIENT(S): Women (n = 159) planning an FER cycle at the Oxford Fertility Unit, aged <40 years at the time their embryos were frozen; with at least one blastocyst or two cleavage-stage embryos in storage; regular ovulatory cycles; and at most two previous FER cycles. INTERVENTION(S): Eligible participants were recruited and randomized between March 2010 and July 2012 into one of two standard FER treatment groups: natural (n = 80) menstrual (Natural) or GnRH agonist/HRT (n = 79) cycles. MAIN OUTCOME MEASURE(S): Live birth rate after replacement of frozen-thawed embryos, clinical pregnancy rate, implantation rate, and cycle cancellations. RESULT(S): A total of 159 women were randomized (80 Natural; 79 HRT), and 145 had ET and completed the study (72 Natural; 73 HRT). Pregnancy outcomes were not significantly different between the two groups. The live birth rates were 26.3% (Natural) and 31.7% (HRT) per randomized patient. Per ET/protocol the live birth rates were 29.2% and 34.2%. The implantation rates were 24.3% and 26.0%, and there were three twin births in the Natural and five in the HRT arms. CONCLUSION(S): The findings of this pilot study support the suggestion that for women with ovulatory cycles undergoing FER, the outcomes are similar between natural and HRT protocols. CLINICAL TRIAL REGISTRATION NUMBER: NCT00843570. Registered at www.clinicaltrials.gov.

Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection.

OBJECTIVE: To study the relationship of total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta, with fertilization rates after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). DESIGN: Laboratory study; controls vs. patients after IVF (n = 27) or ICSI (n = 17) treatment. SETTING: Fertility center. PATIENT(S): A total of 44 semen samples, subjected to either IVF or ICSI treatment. Oocyte collection, ICSI or IVF, determination of sperm concentration and motility, and immunocytochemical analyses of phospholipase C zeta (PLCζ). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Percentages of sperm exhibiting PLCζ. RESULT(S): Significant positive correlation between ICSI fertilization rates and total levels, localization patterns, and the proportion (percentage) of sperm exhibiting PLCζ. Total levels, localization patterns, and the proportion of sperm exhibiting PLCζ are correlated with fertilization rates for ICSI, but not for IVF. CONCLUSION(S): Evaluating total levels, localization patterns, and proportions of PLCζ may represent a useful diagnostic tool for clinical purposes in men for whom IVF is not advised or has previously failed. This clinical study further supports the fundamental role of PLCζ in the oocyte activation process.

Evaluation of the use and handling of three different pen systems considered for in vitro fertilization treatment.

OBJECTIVE: The objective of this study was to assess and compare the features of the Bemfola, Gonal-f and Puregon injection pens. METHODS: Females who intended to undergo hormonal treatment received the three different pens in a randomized, consecutive sequence. For each of the pens, the potential patients completed an Injection Pen Assessment Questionnaire, as well as a questionnaire comparing the handling, convenience and preference among the three pens. RESULTS: The mean score on the visual analogue scale (VAS) for the Bemfola pen (BP) was 77.8 ± 14.0; for the Puregon pen (PP), 72.1 ± 12.4; and for the Gonal-f pen (GP), 68.6 ± 16.4. The BP was superior to both competitor devices in pen size, inconspicuousness, ease of use and dose changing; no significant differences to both competitor pens were observed in the way the pen looks, the way the pen feels and the ease of injection of the volume. The 'overall' assessment was significantly better for the BP when compared to the GP (p = 0.0019), while no significant difference was observed between the BP and the PP. CONCLUSIONS: This study demonstrated significantly higher ratings for pen size, inconspicuousness, ease of use and dose adjustment for the BP compared to other marketed pens.

The case for aromatase inhibitors use in oncofertility patients. Should aromatase inhibitors be combined with gonadotropin treatment in breast cancer patients undergoing ovarian stimulation for fertility preservation prior to chemotherapy? A debate.

Breast cancer is one of the hormone-dependent cancers that may be adversely affected by elevated oestrogen or progesterone concentrations, particularly the endocrine active (hormone receptor positive) breast cancers. Treatment for breast cancer patients aimed at fertility preservation, includes ovarian hyperstimulation, the harvest of oocytes, and subsequent cryopreservation of oocytes or embryos. Classically, gonadotrophins have been used effectively for ovulation induction, a treatment often accompanied by high blood oestrogen concentrations produced by the hyperstimulated granulosa cells. Despite the uncertainty which surrounds this issue and the lack of clear-cut clinical evidence, it is still of major concern that these ensuing high hormone levels might be associated with a high risk of recurrence of the cancer. A growing number of clinical studies have strongly suggested the benefits of using aromatase inhibitors in infertility treatment, both as single agents or as adjuncts to FSH-containing ovulation induction regimes in reproductive medicine. Combining gonadotrophins with aromatase inhibitors would augment the stimulation effect, with a reduced increase in serum concentrations of estradiol. We propose to open a debate over the use of aromatase inhibitors in combination with FSH in ovulation induction treatment of breast cancer oncofertility patients. As the safety of aromatase inhibitors such as letrozole has recently been demonstrated in several studies, and there is growing concern over the possible detrimental effects of high estradiol levels on breast cancer cells (at least in mouse models), the co-administration of letrozole in these patients would reduce both the high supraphysiologic serum levels of estradiol and the intratumoral in situ production of oestrogen. However, since it is unlikely that a well-founded evidence-based justification of this treatment will be formulated in the near future, based on well-designed prospective randomised controlled trials, we advocate a wider use of aromatase inhibitors in combination with gonadotrophins in breast cancer patients, especially those with hormone-receptor-positive tumours.

Variance in total levels of phospholipase C zeta (PLC-ζ) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability.

OBJECTIVE: To examine whether similar levels of phospholipase C zeta (PLC-ζ) protein are present in sperm from men whose ejaculates resulted in normal oocyte activation, and to examine whether a predominant pattern of PLC-ζ localization is linked to normal oocyte activation ability. DESIGN: Laboratory study. SETTING: University laboratory. PATIENT(S): Control subjects (men with proven oocyte activation capacity; n = 16) and men whose sperm resulted in recurrent intracytoplasmic sperm injection failure (oocyte activation deficient [OAD]; n = 5). INTERVENTION(S): Quantitative immunofluorescent analysis of PLC-ζ protein in human sperm. MAIN OUTCOME MEASURE(S): Total levels of PLC-ζ fluorescence, proportions of sperm exhibiting PLC-ζ immunoreactivity, and proportions of PLC-ζ localization patterns in sperm from control and OAD men. RESULT(S): Sperm from control subjects presented a significantly higher proportion of sperm exhibiting PLC-ζ immunofluorescence compared with infertile men diagnosed with OAD (82.6% and 27.4%, respectively). Total levels of PLC-ζ in sperm from individual control and OAD patients exhibited significant variance, with sperm from 10 out of 16 (62.5%) exhibiting levels similar to OAD samples. Predominant PLC-ζ localization patterns varied between control and OAD samples with no predictable or consistent pattern. CONCLUSION(S): The results indicate that sperm from control men exhibited significant variance in total levels of PLC-ζ protein, as well as significant variance in the predominant localization pattern. Such variance may hinder the diagnostic application of quantitative PLC-ζ immunofluorescent analysis.

Motile sperm organelle morphology evaluation-selected globozoospermic human sperm with an acrosomal bud exhibits novel patterns and higher levels of phospholipase C zeta.

STUDY QUESTION: Does motile sperm organelle morphology examination (MSOME) affect levels and localization patterns of the oocyte activation factor phospholipase C zeta (PLCζ) in globozoospermic sperm with and without an acrosomal bud? SUMMARY ANSWER: MSOME identified round-headed globozoospermic sperm with increased levels of PLCζ relative to sperm from the same sample that did not undergo MSOME, and identified novel patterns of PLCζ localization in sperm exhibiting an acrosomal bud. WHAT IS KNOWN ALREADY: Absence or reduction in the level of PLCζ in the sperm head, abnormal localization patterning, or defective functional ability as a result of PLCζ gene mutation, have been linked to certain types of human male factor infertility in which oocyte activation is deficient. It has been determined that a subpopulation of sperm (1%) from a patient exhibiting 100% globozoospermia presented with an acrosome bud upon MSOME. A cycle of intracytoplasmic morphologically selected sperm injection, carried out with sperm exhibiting an acrosomal bud led to pregnancy and birth of a healthy baby boy, without the use of assisted oocyte activation (AOA). STUDY DESIGN, SIZE, DURATION: Immunofluorescent analysis of PLCζ in globozoospermic sperm from three patients, before and after MSOME. PARTICIPANTS/MATERIALS, SETTING, METHODS: Quantitative immunofluorescence was used to investigate PLCζ levels and localization patterns in individual sperm (n = 1 patient) identified by MSOME and isolated by micromanipulation, and presenting with and without the acrosomal bud. A secondary aim was to investigate levels and localization patterns of PLCζ in sperm before and after MSOME from two other globozoospermic men. MAIN RESULTS AND THE ROLE OF CHANCE: Non-globozoospermic control sperm exhibited characteristic localization patterns of PLCζ immunofluorescence. Completely round-headed globozoospermic sperm from patients 1-3 were either devoid of PLCζ immunofluorescence, or exhibited an abnormal, punctate, pattern of PLCζ localization. PLCζ immunofluorescence in sperm exhibiting an acrosomal bud was observed in the midpiece with varying fluorescent intensity and was detected in 28.5% of such sperm. The majority of sperm with an acrosomal bud (43.0%) exhibited punctate patterns of PLCζ localization within the sperm head. A further 28.5% of sperm exhibited PLCζ in both the head and the midpiece. Total levels of PLCζ, and the proportions of sperm exhibiting PLCζ immunoreactivity, showed significant variance (P ≤ 0.05) amongst control [45.8 arbitrary units (a.u.) and 95.7%, respectively], non-MSOME-selected (25.9 a.u. and 46.1%, respectively) and MSOME-selected globozoospermic sperm (33.4 a.u. and 65.0%, respectively). Total levels of PLCζ immunofluorescence, and proportions of sperm exhibiting PLCζ immunoreactivity, in control sperm was significantly higher (P≤ 0.05) compared with non-MSOME-selected sperm, but not significantly different from MSOME-selected sperm. LIMITATIONS, REASONS FOR CAUTION: The low numbers of sperm analysed may not be ideal for conclusive statistical analysis. Evaluation of the effects of MSOME on morphologically normal sperm would confirm conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The present findings provide hope for the future treatment of globozoospermia without the need for AOA, and provide further evidence for the clinical application of PLCζ as a therapeutic and prognostic tool. STUDY FUNDING/COMPETING INTEREST(S): The research described herein was funded by the Nuffield Department of Obstetrics and Gynaecology, University of Oxford. The authors report no conflict of interest.

In vitro maturation or in vitro fertilization for women with polycystic ovaries? A case-control study of 194 treatment cycles.

OBJECTIVE: To compare the outcome of unstimulated in vitro maturation (IVM) and routine IVF/intracytoplasmic sperm injection (ICSI) for women with polycystic ovaries (PCO). DESIGN: Retrospective case-control study. SETTING: Fertility unit. PATIENT(S): Ninety-seven patients undergoing IVM were compared with 97 patients undergoing IVF. All had PCO and matched for age, infertility diagnosis, and ovulatory status. INTERVENTION(S): In vitro maturation cycles were unstimulated and hCG was administered 35-40 hours before oocyte retrieval. Oocytes were matured in vitro for 24-48 hours before insemination by ICSI. Endometrial priming with E(2) and P was commenced from the day of egg retrieval and one to two embryos were transferred on days 2-5 of development. Standard long protocol IVF/ICSI was used in the control group. MAIN OUTCOME MEASURE(S): Live birth rate per cycle and ovarian hyperstimulation syndrome (OHSS) rate. RESULT(S): Overall, 65% of IVM eggs matured in vitro in the IVM group. Implantation rates were significantly higher in the IVF group (19.4% vs. 12.9%) as clinical pregnancy rates (50.5% vs. 19.6%) and live birth rates (44.3% vs. 16.5%) than in the IVM group. The OHSS rate was significantly higher in the IVF group (8.2% vs. 0%). CONCLUSION(S): In vitro maturation is a safer and simpler alternative to conventional IVF for women with PCO. It avoids difficulties of gonadotropin stimulation and the risk of OHSS but has a significantly lower live birth rate. Current research projects aim to close the success gap between IVM and IVF.

Do women with ovaries of polycystic morphology without any other features of PCOS benefit from short-term metformin co-treatment during IVF? A double-blind, placebo-controlled, randomized trial.

BACKGROUND: Women with ovaries of polycystic morphology (PCO), without any other features of polycystic ovary syndrome (PCOS), respond similarly to women with PCOS when stimulated with exogenous gonadotrophins, and both groups share various endocrinological disturbances underlying their pathology. In women with PCOS, metformin co-treatment during IVF has been shown to increase pregnancy rates and reduce the risk of ovarian hyperstimulation syndrome (OHSS). The aim of this study was to investigate whether metformin co-treatment before and during IVF can also increase the live birth rate (LBR) and lower severe OHSS rates for women with PCO, but no other manifestations of PCOS. METHODS: This study was a double-blind, multi-centre, randomized, placebo-controlled trial. The study population included 134 women with ovulatory PCO (and no evidence of clinical or biochemical hyperandrogenism) undergoing IVF treatment at three tertiary referral IVF units. The primary outcome was LBR. RESULTS: In total, 134 women were randomized, 69 to metformin and 65 to placebo. There were no statistically significant differences between the two groups in baseline characteristics. With regard to IVF outcome, no significant improvements were found in the metformin group when compared with the placebo group. In particular, there was no difference between the groups in rates of live birth [metformin n = 27 (39.1%), placebo n = 30 (46.2), (95% confidence interval 0.38, 1.49, odds ratio = 0.75)], clinical pregnancy [metformin n = 29 (42.0%), placebo n = 33 (50.8%)] or severe OHSS [metformin n = 6 (8.7%), placebo n = 5 (7.7%)]. CONCLUSIONS: There appears to be no benefit in metformin co-treatment before and during IVF in women with PCO without any other features of PCOS. Clinical Trials.gov: NCT01046032.

The elephant in the room: quality control of endometriosis data.

With the steadily increasing volume of endometriosis articles, and titles and abstracts readily available online, there is a growing risk that references are cited without the full articles having been read by the author(s) or by referees. Too often the titles and statements in abstracts are not supported by data in the published articles. Therefore, the peer-review process should direct extra attention to titles and abstracts to ensure that they are supported by data in the manuscript. Moreover, it is suggested that authors explicitly indicate which references have been read in full. To support the secondary peer-review process, we urge open-access journals to welcome letters to the editor and publish them instead of quietly "burying" them on the Internet.

IVF outcome in women with PCOS, PCO and normal ovarian morphology.

OBJECTIVE: To examine the outcome of IVF in women who have normal ovaries, ovulatory PCO or PCOS. STUDY DESIGN: Analysis of a prospectively collected database in an assisted conception unit in a university teaching hospital including 290 women <37 years of age undergoing their first IVF cycle. The main outcome measure was severe OHSS requiring hospitalization. RESULTS: Severe OHSS rates were significantly higher in women with PCO (12.6%) and PCOS (15.4%) compared to those with normal ovaries (2.7%). Coasting was used significantly more often. Live birth rates per cycle started are similar among women with PCO (38%), PCOS (37%) and normal ovaries (40%). CONCLUSION: Women with ovaries of polycystic morphology are at increased risk of developing severe OHSS and of requiring avoidance techniques such as coasting, regardless of ovulatory status. However, live birth rates per cycle are similar to women with normal ovaries.

Effects of gonadotrophin releasing hormone analogues on human endometrial stromal cells and embryo invasion in vitro.

BACKGROUND: Gonadotrophin releasing hormone (GnRH) analogues are widely used in IVF programmes as a method of suppressing the luteinizing hormone (LH) surge prior to ovarian stimulation, but their roles outside the pituitary remain relatively unknown. A 2002 Cochrane review (Al-Inany et al. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev 2006;3:CD001750) described lower pregnancy rates in women administered with GnRH antagonist, compared with those using an agonist, as part of an IVF programme, despite the fact that GnRH antagonist is a more effective repressor of LH. This study aimed to analyse the in-vitro effects of GnRH analogues on the decidualizing endometrium, blastocyst invasion and GnRH receptor expression in fertile women. METHODS: We analysed the in-vitro decidualization capacity of endometrial stromal cells, derived from fertile women during the implantation window, in the presence of GnRH analogues. The influence of GnRH analogues on GnRH receptor expression and blastocyst invasion was assessed by in-vitro assays of biomedical marker secretion, immunoblots and blastocyst attachment to the stromal extracellular matrix. RESULTS: We demonstrate that, at the concentrations and time periods used, GnRH analogues did not significantly influence the extent of decidualization of endometrial stromal cells. In addition, no adverse effect of GnRH analogues was seen on human blastocyst invasion. CONCLUSIONS: We suggest that GnRH analogues affect neither the capacity of the endometrium to support invasion nor the invasive potential of the blastocyst in the early stages of implantation.

A large Northern European observational study of follitropin alpha filled-by-mass pre-filled pen.

This prospective observational post-marketing survey aimed at studying the efficacy and convenience of the follitropin alpha filled-by-mass (FbM) pre-filled pen for patients in routine use. These data were analysed among 3196 non-selected treatment cycles and couples in seven Northern European countries. Valuable information was also obtained regarding the routine assisted reproduction treatment protocols used in Northern Europe. Out of 3196 cycles, human chorionic gonadotrophin (HCG) was administered in 3104 (97.2%), and an embryo transfer was carried out in 2766 cycles (86.5%). A positive HCG was recorded in 997 cycles (31.2% per started cycle and 36.0% per embryo transfer). The overall clinical pregnancy rate was 23.1% (738/3196) and per embryo transfer it was 26.7% (738/2766), with a miscarriage rate of 3.4% (95/2766) per embryo transfer or 9.5% (95/997) per positive HCG. Among the 732 elective single embryo transfers (eSET), the rate of positive HCG was 38.0% and the clinical pregnancy rate was 29.6%, suggesting that eSET is a valuable option in routine assisted reproduction. Although minor differences were observed between countries, the follitropin alpha FbM pre-filled pen proved clinically effective, was generally well tolerated, and both the women and nurses/midwives found the training easy.

Adhesions are common and costly after open pouch surgery.

PURPOSE: Open ileal pouch surgery leads to high rates of adhesive small-bowel obstruction (SBO). A laparoscopic approach may reduce these complications. We aimed to review the incidence of adhesive SBO-related complications after open pouch surgery and to model the potential financial impact of a laparoscopic approach purely as an adhesion prevention strategy. MATERIALS AND METHODS: We reviewed cases of open ileal pouch patients kept on a database and examined annually. Case notes were studied for episodes of adhesive SBO requiring admission or reoperation. Similar parameters were studied in a small series undergoing laparoscopic pouch surgery. The financial burden of the open access complications was estimated and potential financial impact of a laparoscopic approach modeled. RESULTS: Two hundred seventy-six patients were followed up after open surgery (median, 6.3; range, 0.2-20.1 years). There were 76 (28%) readmissions (median length of stay, 7.4 days) in 53 patients (19%) and 28 (10%) reoperations (43% within 1 year). Laparoscopic patients required less adhesiolysis at second-stage surgery (0% vs 36%, p < 0.0001) and had less SBO episodes within 12 months of surgery (0% vs 14%, p < 0.0001) than open patients. Modeling a laparoscopic approach cost $1,450 and saved $3,282, thus netting $1,832 per pouch constructed. CONCLUSION: Open ileal pouch surgery results in significant cumulative long-term access-related complications, particularly adhesions. These impose a large medical burden on patients and financial burden on health-care systems, all of which may be recouped by a laparoscopic approach, despite higher theater costs.

Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression.

BACKGROUND: Endometriosis, classified as the presence of endometrial cells in ectopic sites, is a debilitating disease causing pain and infertility in approximately 10% of women of reproductive age. It is associated with the aberrant expression of extracellular matrix (ECM) components and their receptors, integrins. METHODS: We analysed the expression of integrins in stromal cells derived from peritoneal, ovarian and deeply infiltrating endometriotic lesions and from endometrium from women with and without endometriosis in vitro, using quantitative immunocytochemistry. The adhesive and proliferative capacity of each of the cell types in response to ECM components was assessed by in vitro assays of cell attachment and DNA synthesis. RESULTS: We demonstrate that eutopic and ectopic endometrial stromal cells from women with endometriosis exhibit an aberrant integrin profile in vitro compared with stromal cells derived from healthy controls. In addition, the former display increased adhesion and proliferative capacity in response to specific ECM components. CONCLUSIONS: We propose that the increased adhesive and proliferative potential of cells from endometriotic lesions may be a key feature in the pathogenesis of endometriosis. Furthermore, the elevated responsiveness of eutopic cells from women with endometriosis may contribute to the predisposition of some women to the disease.

Azoospermia: is sample centrifugation indicated? A national survey of practice and the Oxford experience.

OBJECTIVE: Some men with azoospermia on general laboratory testing have low quantities of sperm in the ejaculate that can only be identified through sample centrifugation and careful examination of the pellet droplets (extended sperm preparation [ESP]). Such sperm can be used for IVF-ICSI as an alternative to either surgical sperm retrieval (SSR) or donor sperm. The aims of the present study were to: 1) assess UK IVF clinic practice with regard to ESP in men with azoospermia; and 2) to analyze the outcome of ESP and SSR in azoospermic men attending the Oxford Fertility Unit. DESIGN: National survey of all 70 IVF units plus chart review. SETTING: Assisted conception unit. PATIENT(S): One hundred twenty-two azoospermic men referred to the Oxford Fertility Unit. MAIN OUTCOME MEASURE(S): Proportions of UK IVF clinics performing ESP for azoospermia. Proportions of azoospermic men in Oxford with sperm identified at ESP and, if necessary, SSR. Relationship between serum FSH and outcome. RESULT(S): In part 1 of the study, 55 (79%) of the 70 UK IVF clinics returned completed questionnaires. Fifty clinics (91%) routinely performed ESP for men with azoospermia on general laboratory testing, four clinics (7%) proceeded straight to SSR without prior ESP, and one clinic varied in their approach. When clinics were asked whether they used serum FSH levels when considering whether to proceed to SSR 28 (51%) did, 9 (16%) did not, and 18 (33%) varied in their approach. The value placed on testicular volume similarly varied. Part 2 of the study included 122 men referred to the Oxford Fertility Unit with azoospermia on general laboratory testing. Eighty-seven men underwent ESP. Motile sperm was found, cryopreserved, and later used during IVF-ICSI treatment in 19 men (22%). Eighty-one men underwent SSR (after either a negative ESP or declining ESP). Viable sperm was found in 66 men undergoing SSR (81%). There was a statistically significant relationship between serum FSH and the chance of retrieving sperm with SSR (P=0.002) but not with ESP. CONCLUSION(S): The majority (91%) of IVF clinics in the UK routinely perform ESP in men with azoospermia on general testing. Only half routinely used serum FSH levels as predictors of SSR outcome. The value of ESP is confirmed by our findings in Oxford. Twenty-two percent of men with azoospermia on general laboratory testing had sufficient sperm found at ESP to proceed to IVF-ICSI without resorting to the use of either SSR or donor sperm. Serum FSH levels were not related to the chance of finding sperm during ESP but were related to the outcome of SSR. Our results suggest that ESP should be considered for all men with azoospermia and no apparent obstruction.

The Duarte (N314D) variant in the GALT gene has no effect on in vitro fertilization outcome.

We assessed the effect of the Duarte (N314D) variant in the GALT gene on in vitro fertilization outcome measures. Our data do not definitely exclude variants in the GALT gene as factors influencing outcome, but the lack of suggestive evidence makes it difficult to justify a larger, more definitive study.