Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study.

PURPOSE: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. METHODS: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. RESULTS: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09). CONCLUSION: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. TRIAL REGISTRATION: Clinical trial registration number: NCT03354793.

Is a freeze-all policy the optimal solution to circumvent the effect of late follicular elevated progesterone? A multicentric matched-control retrospective study analysing cumulative live birth rate in 942 non-elective freeze-all cycles.

STUDY QUESTION: Is late follicular elevated progesterone (LFEP) in the fresh cycle hindering cumulative live birth rates (CLBRs) when a freeze only strategy is applied? SUMMARY ANSWER: LFEP in the fresh cycle does not affect the CLBR of the frozen transfers in a freeze only approach, nor the embryo freezing rate. WHAT IS KNOWN ALREADY: Ovarian stimulation promotes the production of progesterone (P) which has been demonstrated to have a deleterious effect on IVF outcomes. While there is robust evidence that this elevation produces impaired endometrial receptivity, the impact on embryo quality remains a matter of debate. In particular, previous studies have shown that LFEP is associated with a hindered CLBR. However, most clinical insight on the effect of progesterone on embryo quality in terms of CLBRs have focused on embryo transfers performed after the fresh transfer, thus excluding the first embryo of the cohort. To be really informative on the possible detrimental effects of LFEP, evidence should be derived from freeze-all cycles where no fresh embryo transfer is performed in the presence of progesterone elevation, and the entire cohort of embryos is cryopreserved. STUDY DESIGN, SIZE, DURATION: This was a matched case-control, multicentre (three centres), retrospective analysis including all GnRH antagonist ICSI cycles in which a freeze all (FA) policy of embryos on day 3/5/6 of embryonic development was applied between 2012 and 2018. A total of 942 patients (471 cases with elevated P and 471 matched controls with normal P values) were included in the analysis. Each patient was included only once. PARTICIPANTS/MATERIALS, SETTING, METHODS: The sample was divided according to the following P levels on the day of ovulation triggering: <1.50 ng/ml and ≥1.50 ng/ml. The matching of the controls was performed according to age (±1 year) and number of oocytes retrieved (±10%). The main outcome was CLBR defined as a live-born delivery after 24 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: The baseline characteristics of the two groups were similar. Estradiol levels on the day of trigger were significantly higher in the elevated P group. There was no significant difference in terms of fertilisation rate between the two groups. The elevated P group had significantly more cleavage stage frozen embryos compared to the normal P group while the total number of cryopreserved blastocyst stage embryos was the same. The CLBR did not differ between the two study groups (29.3% and 28.2% in the normal versus LFEP respectively, P = 0.773), also following confounder adjustment using multivariable GEE regression analysis (accounting for age at oocyte retrieval, total dose of FSH, progesterone levels on the day of ovulation trigger, day of freezing, at least one top-quality embryo transferred and number of previous IVF cycles, as the independent variables). LIMITATIONS, REASONS FOR CAUTION: This is a multicentre observational study based on a retrospective data analysis. Better extrapolation of the results could be validated by performing a prospective analysis. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study demonstrating that LFEP in the fresh cycle does not hinder CLBR of the subsequent frozen cycles in a FA approach. Thus, a FA strategy circumvents the issue of elevated P in the late follicular phase. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. Throughout the study period and manuscript preparation, authors were supported by departmental funds from: Centre for Reproductive Medicine, Brussels, Belgium; Infertility Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Centro Scienze Natalità, San Raffaele Scientific Institute, Milan, Italy; and IVI-RMA, Lisbon, Portugal. E.S. has competing interests with Ferring, Merck-Serono, Theramex and Gedeon-Richter outside the submitted work. E.P. reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from MSD and grants from IBSA outside the submitted work. All the other authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Do we trust scientific evidence? A multicentre retrospective analysis of first IVF/ICSI cycles before and after the OPTIMIST trial.

STUDY QUESTION: Has the practice of individualizing the recombinant-FSH starting dose been superseded after the largest randomized controlled trial (RCT) in assisted reproduction technology (ART), the OPTIMIST trial? SUMMARY ANSWER: The OPTIMIST trial has influenced our ART daily practice to a limited degree, but adherence is still generally poor. WHAT IS KNOWN ALREADY: Although the 'one size fits all' approach has been discouraged for decades by most authors, the OPTIMIST study group demonstrated in a large prospective RCT that, in general, dosage individualization does not improve the prospects for live birth, although it may decrease ovarian hyperstimulation syndrome (OHSS) risk in expected high responders. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of all first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles from 1st January 2017 to 31st December 2018, before and after the OPTIMIST publication on November 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two thousand six hundred and seventy-seven patients, between 18 and 42 years old, undergoing their first IVF-ICSI cycle in seven Italian fertility centres, were included. Patients were allocated to three groups according to their ovarian reserve markers: predicted poor ovarian responders (POR), predicted normo-responders (NR) and expected hyper-responders (HRs). MAIN RESULTS AND THE ROLE OF CHANCE: Between 2017 and 2018, there was an overall increase in prescription of the standard 150 IU dose proposed by the OPTIMIST trial and a reduction in the use of a starting dose >300 IU. After subgroup analysis, the decrease in doses >300 IU remained significant in the POR and NR sub-groups. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study. Physicians need time to adapt to new scientific evidence and a comparison between 2017 and 2019 may have found a greater impact of the Optimist trial, although other changes over the longer time span might have increased confounding. We cannot be sure that the observed changes can be attributed to knowledge of the OPTIMIST trial. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians may be slow to adopt recommendations based on RCTs; more attention should be given to how these are disseminated and promoted. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. E.P. reports grants and personal fees from MSD, grants from Ferring, from IBSA, grants and personal fees from Merck, grants from TEVA, grants from Gedeon Richter, outside the submitted work. E.S. reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from Theramex, outside the submitted work. All other authors do not have conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Endometriosis: seeking optimal management in women approaching menopause.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Alcohol intake and semen variables: cross-sectional analysis of a prospective cohort study of men referring to an Italian Fertility Clinic.

BACKGROUND: The association between alcohol intake and male reproductive function is still controversial. In the frame of a prospective cohort study, designed to investigate the relation between life style and fertility, we performed a cross-sectional analysis of semen quality. METHODS: Men of subfertile couples, referring to an Italian Infertility Unit and eligible for assisted reproductive techniques (ARTs), were asked about their lifestyle: BMI, smoking, caffeine intake, occupational and leisure physical activity (PA) and alcohol intake in the last year before ART procedure. Semen volume, sperm concentration, total sperm count and sperm motility were determined. Age, risk factors for impaired male fertility, caffeine, smoking, leisure PA, days of abstinence and daily calories intake were accounted for in the analyses. RESULTS: Between September 2014 and December 2016, we enrolled 323 male patients, mean age 39.3 years. Thirty-one (9.6%) were abstainers, 97 (30.0%) drank <1-3, 98 (30.3%) 4-7 and 97 (30.0%) ≥8 alcohol units per week. As compared to men drinking <1-3 units per week, median semen volume was higher in the 4-7 units/week group (3.0 mL, interquartile range, IQR, 2.0-4.0 vs. 2.4 mL, IQR 1.7-3.5), as well as total sperm count (87.9 mil/mL, IQR 20.2-182.1 vs. 51.5 mil/mL, IQR 15.2-114.7). Association with sperm concentration was also significant, with a U-shaped trend in groups of alcohol intake. After adjusting for potential confounders, these relations were confirmed. Similar patterns were observed in subgroups of leisure PA and risk factors for impaired male fertility, although these estimates often lacked statistical significance, presumably because of low sample size. CONCLUSIONS: Moderate alcohol intake appears positively associated to semen quality in male partners of infertile couples undergoing ARTs.

Multifactorial analysis of the stochastic epigenetic variability in cord blood confirmed an impact of common behavioral and environmental factors but not of in vitro conception.

Background: An increased incidence of imprint-associated disorders has been reported in babies born from assisted reproductive technology (ART). However, previous studies supporting an association between ART and an altered DNA methylation status of the conceived babies have been often conducted on a limited number of methylation sites and without correction for critical potential confounders. Moreover, all the previous studies focused on the identification of methylation changes shared among subjects while an evaluation of stochastic differences has never been conducted. This study aims to evaluate the effect of ART and other common behavioral or environmental factors associated with pregnancy on stochastic epigenetic variability using a multivariate approach. Results: DNA methylation levels of cord blood from 23 in vitro and 41 naturally conceived children were analyzed using the Infinium HumanMethylation450 BeadChips. After multiple testing correction, no statistically significant difference emerged in the number of cord blood stochastic epigenetic variations or in the methylation levels between in vitro- and in vivo-conceived babies. Conversely, four multiple factor analysis dimensions summarizing common phenotypic, behavioral, or environmental factors (cord blood cell composition, pre or post conception supplementation of folates, birth percentiles, gestational age, cesarean section, pre-gestational mother's weight, parents' BMI and obesity status, presence of adverse pregnancy outcomes, mother's smoking status, and season of birth) were significantly associated with stochastic epigenetic variability. The stochastic epigenetic variation analysis allowed the identification of a rare imprinting defect in the locus GNAS in one of the babies belonging to the control population, which would not have emerged using a classical case-control association analysis. Conclusions: We confirmed the effect of several common behavioral or environmental factors on the epigenome of newborns and described for the first time an epigenetic effect related to season of birth. Children born after ART did not appear to have an increased risk of genome-wide changes in DNA methylation either at specific loci or randomly scattered throughout the genome. The inability to identify differences between cases and controls suggests that the number of stochastic epigenetic variations potentially induced by ART was not greater than that naturally produced in response to maternal behavior or other common environmental factors.

Time to redefine endometriosis including its pro-fibrotic nature.

Endometriosis is currently defined as presence of endometrial epithelial and stromal cells at ectopic sites. This simple and straightforward definition has served us well since its original introduction. However, with advances in disease knowledge, endometrial stromal and glands have been shown to represent only a minor component of endometriotic lesions and they are often absent in some disease forms. In rectovaginal nodules, the glandular epithelium is often not surrounded by stroma and frequently no epithelium can be identified in the wall of ovarian endometriomas. On the other hand, a smooth muscle component and fibrosis represent consistent features of all disease forms. Based on these observations, we believe that the definition of endometriosis should be reconsidered and reworded as 'A fibrotic condition in which endometrial stroma and epithelium can be identified'. The main reasons for this change are: (1) to foster the evaluation of fibrosis in studies on endometriosis pathogenesis using animal models; (2) to limit potential false negative diagnoses if pathologists stick stringently to the current definition of endometriosis requiring the demonstration of endometrial stromal and glands; (3) to consider fibrosis as a potential target for treatment in endometriosis. This opinion article is aimed at boosting the attention paid to a largely neglected aspect of the disease. We hope that targeting the fibrotic process might increase success in developing new therapeutic approaches.

Mental health in women with endometriosis: searching for predictors of psychological distress.

STUDY QUESTION: What factors affect the mental health of women with endometriosis? SUMMARY ANSWER: Not only pelvic pain, but also individual characteristics (i.e. self-esteem, body esteem and emotional self-efficacy), time from diagnosis and intimate relationship status influence the psychological health of endometriosis patients. WHAT IS KNOWN ALREADY: The negative impact of endometriosis on mental health has been widely demonstrated by the research literature, along with the fact that presence and severity of pelvic pain are associated with anxiety and depression. However, endometriosis is a complex multidimensional disease and factors other than pelvic pain, including individual differences, may contribute to explain the variability in women's mental health. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was conducted between 2015 and 2017 at an Italian academic department of obstetrics and gynaecology. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 210 consecutive endometriosis patients (age: 36.7 ± 7.0 years) were included. Demographic and endometriosis-related information was collected. Individual differences were assessed using validated measures evaluating self-esteem, body esteem and emotional self-efficacy. The Hospital Anxiety and Depression Scale (HADS) and the Ruminative Response Scale (RRS) were used to evaluate mental health. MAIN RESULTS AND THE ROLE OF CHANCE: Based on the extant literature, we identified three categories of putative predictors (demographic variables, endometriosis-related factors and individual differences i.e. 'self'), whose psychological impact was examined using a hierarchical multiple regression approach. Being in a stable relationship (coded 1 ['yes'] or 0 ['no']) was associated with decreased rumination (RRS: ß = -0.187; P = 0.002). A shorter time from diagnosis was associated with greater anxiety (HADS-A: ß = -0.177; P = 0.015). Pelvic pain severity and 'self' were associated with all mental health variables (Ps < 0.01). Greater self-esteem, body esteem, and emotional self-efficacy were correlated with better psychological outcomes (Ps < 0.01). LIMITATIONS REASONS FOR CAUTION: Sexual functioning, pregnancy, infertility, cultural differences and gender beliefs have been found to be important in women with endometriosis. In our regression model, we did not test the psychological impact of these variables and this should be acknowledged as an important limitation. Moreover, the cross-sectional (rather than longitudinal) nature of this study does not allow a full examination of the temporal relationship between endometriosis and psychological outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Factors other than pelvic pain can significantly affect the mental health of women with endometriosis, and the role of individual differences requires further investigation. Targeted multidisciplinary interventions should include evaluation and enhancement of self-esteem and self-efficacy to improve women's psychological health. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Not applicable.

Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles.

Cycles with progesterone elevation during controlled ovarian stimulation (COS) for IVF/ICSI are commonly managed with a "freeze-all" strategy, due to a well-recognized detrimental effect of high progesterone levels on endometrial receptivity. However, also a detrimental effect of elevated progesterone on day-3 embryo quality has recently been found with regards to top quality embryo formation rate. Because blastocyst culture and cryopreservation are largely adopted, we deemed relevant to determine whether this detrimental effect is also seen on blastocyst quality on day 5-6. This issue was investigated through a large two-center retrospective study including 986 GnRH antagonist IVF/ICSI cycles and using top quality blastocyst formation rate as the main outcome. Results showed that on multivariate analysis sperm motility (p<0.01) and progesterone levels at ovulation triggering (p = 0.01) were the only two variables that significantly predicted top quality blastocyst formation rate after adjusting for relevant factors including female age, BMI, basal AMH and total dose of FSH used for COS. More specifically, progesterone levels at induction showed an inverse relation with top quality blastocyst formation (correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis identified P level >1.49 ng/ml as the best cut-off for identification of patients at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study is the first to investigate the top quality blastocyst formation rate in relation to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone is associated with lower rates of top quality blastocyst. Hence, the advantages of prolonging COS to maximize the number of collected oocytes might eventually be hindered by a decrease in top quality blastocysts available for transfer, if increasing progesterone levels are observed. This observation extends the results of two recent studies focused on day-3 embryos and deserves further research.

[Conservative management of endometrioma in women undergoing in vitro fertilization]. / Traitement conservateur des endométriomes chez les patientes prises en charge en FIV.

Endometriosis is a chronic disease. The pathogenesis is actually still unclear. Endometriosis is responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical). Among the different phenotypes of endometriosis, the ovarian endometrioma seems to most important lesion in the management of endometriosis-related infertility. Surgical treatment is associated to a decrease of the ovarian reserve and a potential detrimental effect on in vitro fecondation (IVF) outcomes. Thus, the choice between conservative or surgical management of endometrioma before IVF is actually debated. The advantages and drawback of surgical and conservative management should be discussed before to plan the treatment. In the present review, we aimed at assessing the risks of a conservative management of endometrioma as compared to surgery before IVF.

Pregnancy outcome after a first episode of cerebral vein thrombosis.

Essentials Little is known about recurrences and pregnancy outcome after cerebral vein thrombosis (CVT). We studied a cohort of pregnant women with CVT. Women with CVT appear at increased risk of late obstetrical complications despite prophylaxis. Risks of recurrent thrombosis and bleeding in women on heparin prophylaxis while pregnant are low. SUMMARY: Background The risk of recurrent thrombosis and bleeding episodes in women with previous cerebral vein thrombosis (CVT) on antithrombotic prophylaxis with low-molecular-weight heparin (LMWH) during pregnancy is not established and little information is available on pregnancy outcome. Objectives The aims of this study were to evaluate the risk of obstetrical complications, recurrent venous thrombosis and bleeding in a cohort of pregnant women on LMWH after a first episode of CVT. In addition, to estimate the relative risk of obstetrical complications, patients were compared with healthy women without thrombosis and with at least one pregnancy in their life. Patients We studied a cohort of 52 patients and 204 healthy women. Results The risk of developing late obstetrical complications was 24% (95% CI, 18-38%), leading to a relative risk of 6.09 (95% CI, 2.46-15.05). The risk of miscarriage was not increased. The higher risk of late obstetrical complications in patients appeared unrelated to a previous history of obstetrical complications, to the carriership of thrombophilia abnormalities, or to the presence of co-morbidities. The incidence of termination observed in patients with thrombophilia was double that observed in those without. No recurrent thrombosis or bleeding episodes were observed. Conclusions Women with previous CVT on LMWH prophylaxis during pregnancy have a low risk of developing recurrent thrombosis or bleeding episodes, but seem to have an increased risk of late obstetrical complications.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary.

BACKGROUND: Clinical data suggest that the presence of an ovarian endometrioma may cause per se damage to the surrounding otherwise healthy ovarian tissue. However, the basic research has so far done a limited job in trying to understand the potential detrimental effect of an endometrioma presence in the context of the ovarian physiology. We have reviewed the literature with the aim of characterizing the pathophysiology of the endometrioma focusing mostly on factors and mechanisms potentially affecting the surrounding, otherwise normal, ovarian tissue. METHODS: Comprehensive searches of PUBMED were conducted to identify human studies published from 1991 to 2013 in the English language on the cellular and molecular characterization of the various endometrioma components. RESULTS: An endometrioma contains free iron, reactive oxygen species (ROS), proteolytic enzymes and inflammatory molecules in concentrations from tens to hundreds of times higher than those present in peripheral blood or in other types of benign cysts. The cyst fluid causes substantial changes in the endometriotic cells that it baths from gene expression modifications to genetic mutations The physical barrier between the cyst contents and the normal ovarian tissue is a thin wall composed of the ovarian cortex itself or fibroreactive tissue. ROS potentially permeating the surrounding tissues and proteolytic substances degrading the adjacent areas are likely to cause the substitution of normal ovarian cortical tissue with fibrous tissue in which the cortex-specific stroma is reduced. The fibrosis is associated with smooth muscle metaplasia and followed by follicular loss and intraovarian vascular injury. Follicular density in tissue surrounding the endometriotic cyst was consistently shown to be significantly lower than in healthy ovaries but this pathological change does not appear to be caused by the stretching of surrounding tissues owing to the presence of a cyst. CONCLUSIONS: There is sufficient molecular, histological and morphological evidence, in part deriving from knowledge of the pathophysiology, to support a deleterious effect of the endometrioma on the adjacent ovarian cortical tissue, independent of the mere mechanical stretching owing to its size.

Specific sperm defects are differentially correlated with DNA fragmentation in both normozoospermic and teratozoospermic subjects.

A positive effect of selecting spermatozoa under high magnification during intracytoplasmic sperm injection (ICSI) has been described, but a clear explanation has not been given yet. Previous works have shown that high magnification selected spermatozoa have significantly better chromatin status than unselected cells; on the other hand, it has been reported that spermatozoa with no morphological defects can also be negatively associated with embryo quality and pregnancy outcome attributable to DNA fragmentation. The aim of this study was to investigate whether sperm morphology is correlated with DNA fragmentation, both in normozoospermic and teratozoospermic patients. A prospective cohort study involving 32 subjects was recruited over a 3-month period. Spermatozoa were fixed on a slide for TUNEL assay and evaluated using an epifluorescent light microscope equipped with a video monitor. Single TUNEL-positive or -negative cells were evaluated for morphology at ×4400 magnification. Each spermatozoon was then classified according to morphological normalcy or specific defects. The median percentage of typical forms was 11 and 0%, in the normozoospermic and teratozoospermic groups respectively (p = 0.001). In normozoospermic samples, the percentage of TUNEL-positive morphologically normal spermatozoa was 4%. By comparison, spermatozoa showing a vacuolated head or a small non-oval head had a significantly higher incidence of DNA fragmentation in both groups (12 and 13%, 19 and 13% respectively; p < 0.05). In contrast, spermatozoa showing a pyriform head had a DNA fragmentation rate similar to typical forms (3 and 5%, in normozoospermic and teratozoospermic respectively). This study shows that specific defects evaluated in fixed spermatozoa under high-power magnification are more likely to be associated with DNA fragmentation. High-magnification evaluation of spermatozoa can therefore reduce the probability of selecting cells carrying fragmented DNA during ICSI.

Surgical versus low-dose progestin treatment for endometriosis-associated severe deep dyspareunia II: effect on sexual functioning, psychological status and health-related quality of life.

STUDY QUESTION: Does surgical and low-dose progestin treatment differentially affect endometriosis-associated severe deep dyspareunia in terms of sexual functioning, psychological status and health-related quality of life? SUMMARY ANSWER: Surgery and progestin treatment achieved essentially similar benefits at 12-month follow-up, but with different temporal trends. WHAT IS ALREADY KNOWN: Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. STUDY DESIGN, SIZE, DURATION: Patient preference, parallel cohort study with 12-month follow-up. The effect of conservative surgery at laparoscopy versus treatment with a low dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery was compared. PARTICIPANTS/MATERIALS AND SETTING, METHODS: A total of 51 patients chose repeat surgery and 103 progestin treatment. Variations in sexual function, psychological well-being and quality of life were measured by means of the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression Scale (HADS) and the Endometriosis Health Profile-30 (EHP-30). MAIN RESULTS AND THE ROLE OF CHANCE: Four women in the surgery group and 21 women in the progestin group withdrew from the study for various reasons. Total FSFI scores, anxiety and depression scores and EHP-30 scores improved immediately after surgery, but worsened with time, whereas the effect during progestin use increased more gradually, but progressively, without overall significant between-group differences at 12-month follow-up. A tendency was observed towards a slightly better total FSFI score after surgery at the end of the study period. LIMITATIONS, REASONS FOR CAUTION: Treatments were not randomly allocated, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions. WIDER IMPLICATIONS OF THE FINDINGS: Both surgery and medical treatment with progestins are valuable options for improving the detrimental impact of endometriosis-associated dyspareunia on sexual functioning and quality of life. Women should be aware of the pros and cons of both options to decide which one best suits their needs. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.

Surgical versus medical treatment for endometriosis-associated severe deep dyspareunia: I. Effect on pain during intercourse and patient satisfaction.

STUDY QUESTION: Does surgical or medical treatment for endometriosis-associated severe deep dyspareunia achieve better results in terms of patients' satisfaction (main study outcome), variation of coital pain and frequency of intercourse? SUMMARY ANSWER: Surgery and progestin therapy were equally effective in the treatment of deep dyspareunia in women with rectovaginal endometriosis, whereas medical therapy performed significantly better than excisional treatment in those without deeply infiltrating lesions. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. This study reports a direct comparison between the two treatment options in women with severe pain during intercourse. DESIGN: Patient preference, parallel cohort study with a 12-month follow-up. The effect of conservative surgery at laparoscopy was compared with treatment with a low-dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery. PARTICIPANTS AND SETTING: A total of 51 patients chose repeat surgery and 103 progestin treatment. Patient satisfaction was graded according to a five-category scale. Variations in pain during intercourse were measured by means of a 100-mm visual analogue scale. MAIN RESULTS AND THE ROLE OF CHANCE: In the surgery group, a marked and rapid short-term dyspareunia score reduction was observed, followed by partial recurrence of pain. The pain relief effect of the progestin was more gradual, but progressive throughout the study period. At a 12-month follow-up, the frequency of intercourse per month (mean ± SD) was 4.6 ± 1.8 in the surgery group and 5.3 ± 1.5 in the norethisterone acetate group (P = 0.02). A total of 22/51 (43%) women were satisfied in the surgery group compared with 61/103 (59%) in the progestin group [adjusted odds ratios (OR), 0.36; 95% confidence interval (CI), 0.16-0.82; P = 0.015]. Corresponding figures in women with and without rectovaginal endometriotic lesions were, respectively, 13/24 (54%) versus 18/35 (51%; adjusted OR, 0.77; 95% CI, 0.22-2.67; P = 0.68), and 9/27 (33%) versus 43/68 (63%; adjusted OR, 0.23; 95% CI, 0.07-0.76, P = 0.02). BIAS, CONFOUNDING, AND OTHER REASONS FOR CAUTION: Treatments were not randomly assigned, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions. GENERALIZABILITY TO OTHER POPULATIONS: Caucasian patients able to choose their treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.