Evaluation of fragmented embryos implantation potential using time-lapse technology.

AIM: To examine the implantation potential of fragmented embryos that underwent morphokinetic evaluation in a time-lapse incubator. METHODS: A retrospective study analyzing 4210 Day 5 embryos which were incubated in a time-lapse incubator, between 2013 and 2019. Embryos with more than 5% fragmentation (379 embryos) were included in the study. Embryos selected using the general model and re-examined by our in-house model. Embryo fragmentation percentage was documented from the first cell-division (start fragmentation) to its maximal percentage (final fragmentation), and the ratio between them (fragmentation worsening). Data were analyzed with relation to embryo development, embryos transfer or freezing, clinical pregnancy, and live birth rates. RESULTS: Embryo fragmentation and morphokinetics were found to be independent variables for clinical pregnancy achievements. A higher fragmentation worsening was noted among discarded embryos compared to transferred or frozen embryos (p < 0.0001). Advanced maternal age had a significant negative effect on fragmentation (p < 0.001). Missed abortion rates were similar in fragmented embryos that implanted compared with the overall population. Live birth rates were comparable among embryos which were selected for transfer or freezing by their morphokinetics and had different severity of fragmentation. CONCLUSION: Our study shows that fragmented embryos have a potential to implant and therefore should be selected for transfer. Laboratories which do not use time-lapse incubators for embryo selection, should consider transferring fragmented embryos, since they have an acceptable chance for live birth. Calculation of fragmentation worsening may enhance our ability to predict embryo development. Further research with analysis of more fragmented embryo maybe beneficial. This study was approved by the local ethics committee No. 0010-19 CMC on April 18th, 2019.

Should Intra Cytoplasmic Sperm Injection (ICSI) be the primary insemination method in women undergoing IVF cycles with donor sperm?

PURPOSE: To compare efficacy of Intra Cytoplasmic Sperm Injection (ICSI) with conventional in vitro fertilization (IVF) on treatment outcome in women undergoing in vitro fertilization with donor sperm. METHODS: We examined retrospectively the outcome data from 203 patients undergoing fresh cycles of conventional IVF (cIVF) or ICSI and an additional 77 frozen-thawed embryo transfer (FET) cycles during 2003-2014, all using donor sperm. Fertilization, cleavage, pregnancy and live birth rates and number of high-quality embryos were compared between cIVF and ICSI. RESULTS: Altogether 185 women underwent 479 transfer cycles of fresh embryos (237 cIVF vs. 224 ICSI and 18 "rescue ICSI" cycles). In addition, 77 FET cycles were compared (24 cIVF vs. 53 ICSI cycles). No differences were found between cIVF and ICSI in fertilization, cleavage, pregnancy and live birth rates (92.6% vs 92.2%, 73.4% vs 72.4%, 25.3% vs 27.2% and 13.1% vs 14.7%, respectively). Pregnancy and life birth rates remained similar even when FET cycles were included (25.8% vs 26.2% and 13.1% vs 13.7%, respectively). The use of ICSI was associated with lower rates of high-quality embryos (52.7% vs. 63.3%, P < 0.0001). A multivariate logistic regression analysis found that patients' age, number of transferred embryos and smoking were independently associated with the chance to conceive. Patient age correlated inversely with fertilization rate (r = - 0.13, P < 0.006).Non-smokers were more likely to become pregnant (OR = 2.23, P < 0.012). CONCLUSIONS: Our results show that ICSI does not bypass the age-related decrease in oocyte quality in patients using donor sperm for IVF. Use of ICSI was associated with lower rates of high-quality embryos. The findings imply that ICSI should not be the primary method of insemination in patients undergoing IVF with donor sperm.

The impact of endometrial injury on reproductive outcomes: results of an updated meta-analysis.

BACKGROUND: It is still unclear whether endometrial injury (EI) has a beneficial effect on reproductive outcomes, and if so, the optimal procedure characteristics are not clear. All previous papers concluded that more research is needed, and as additional studies were recently published, the insights on EI have changed significantly. METHODS: Searches were conducted in MEDLINE, Embase, Web of Science, and Cochrane Library, to identify randomized controlled trials examining the EI effect on IVF outcomes in women at least one previous failed cycle. RESULTS: 2015 references were identified through database searching. Ultimately, 17 studies were included, involving 3016 patients. Clinical pregnancy rate (CPR) (RR = 1.19, [95% CI 1.06-1.32], P = .003) and live birth rate (LBR) (RR = 1.18, [95%CI 1.04-1.34], P = .009) were significantly improved after EI. Number of previous failed cycles, maternal age, and hysteroscopy were found to be relevant confounders. Higher CPR and LBR were found when EI was performed twice, while performing EI once did not significantly improve reproductive rates. CONCLUSION: According to the present meta-analysis, EI may be offered to younger patients with few previous failed cycles and should be additionally studied in an RCT comparing different timing and more than one EI before treatment.

Patient-centered elective egg freezing: a binational qualitative study of best practices for women's quality of care.

PURPOSE: How can elective egg freezing (EEF) be made patient centered? This study asked women to reflect on their experiences of EEF, which included their insights and recommendations on the optimal delivery of patient-centered care. METHODS: In this binational, qualitative study, 150 women (114 in the USA, 36 in Israel) who had completed at least one cycle of EEF were recruited from four American IVF clinics (two academic, two private) and three in Israel (one academic, two private) over a two-year period (June 2014-August 2016). Women who volunteered for the study were interviewed by two medical anthropologists. Interviews were audio recorded, transcribed, and entered into a qualitative data management program (Dedoose) for analysis. RESULTS: The majority (85%) of women were without partners at the time of EEF, and thus were undertaking EEF alone in mostly couples-oriented IVF clinics. Following the conceptual framework known as "patient-centered infertility care," we identified two broad categories and eleven specific dimensions of patient-centered EEF care, including (1) system factors: information, competence of clinic and staff, coordination and integration, accessibility, physical comfort, continuity and transition, and cost and (2) human factors: attitude and relationship with staff, communication, patient involvement and privacy, and emotional support. Cost was a unique factor of importance in both countries, despite their different healthcare delivery systems. CONCLUSIONS: Single women who are pursuing EEF alone in the mostly couples-oriented world of IVF have distinct and multifaceted needs. IVF clinics should strive to make best practices for patient-centered EEF care a high priority.

Ten pathways to elective egg freezing: a binational analysis.

PURPOSE: What are the specific pathways that lead women to freeze their eggs? In this binational study, women were asked directly about the life circumstances that led them on the path to elective egg freezing (EEF). METHODS: From June 2014 to August 2016, 150 women (114 in the USA, 36 in Israel) who had completed at least 1 cycle of EEF were interviewed by two medical anthropologists. Study participants were recruited through four American IVF clinics (two academic, two private) and three in Israel (one academic, two private). Interviews were audio-recorded, transcribed verbatim, and entered into a qualitative data management program (Dedoose) for analysis. RESULTS: The majority (85%) of women in the study were without partners, while 15% had partners at the time of EEF. Six pathways to EEF were found among women without partners (being single, divorced, broken up, deployed overseas, single mother, career planner), with career planning being the least common pathway to EEF. Among women with partners, four pathways to EEF were found (relationship too new or uncertain, partner not ready to have children, partner refusing to have children, or partner having multiple partners). With only one exception, the pathways and their frequencies were similar in both countries. CONCLUSIONS: Partnership problems, not career planning, lead most women on pathways to EEF. These pathways should be studied in a variety of national settings, and fertility clinics should offer patient-centered care for single women pursuing EEF in the couples-oriented world of IVF.

Medical egg freezing: the importance of a patient-centered approach to fertility preservation.

PURPOSE: This binational qualitative study of medical egg freezing (MEF) examined women's motivations and experiences, including their perceived needs for patient-centered care in the midst of fertility- and life-threatening diagnoses. METHODS: Forty-five women who had undertaken MEF were interviewed in the USA (33 women) and in Israel (12 women) between June 2014 and August 2016. Interviews lasted approximately 1 h and were conducted by two senior medical anthropologists, one in each country. Women were recruited from four American IVF clinics (two academic, two private) and two Israeli clinics (both academic) where MEF is being offered to cancer patients and women with other fertility-threatening medical conditions. RESULTS: Women who undertake MEF view their fertility and future motherhood as important components of their identities and recovery and, thus, are grateful for the opportunity to pursue fertility preservation. However, women who undergo MEF have special needs, given that they tend to be a "vulnerable" population of young (age < 30), unmarried, resource-constrained women, who are facing not only fertility loss but also the "double jeopardy" of cancer. Through in-depth, qualitative interviews, these women's MEF stories reveal 10 dimensions of care important to fertility preservation, including five "system factors" (information, coordination and integration, accessibility, physical comfort, cost) and five "human factors" (adolescent issues, male partner involvement, family involvement, egg disposition decisions, emotional support). Together, these dimensions of care constitute an important framework that can be best described as "patient-centered MEF." CONCLUSIONS: Women pursuing MEF have special medical needs and concerns, which require particular forms of patient-centered care. This study outlines 10 dimensions of patient-centered fertility preservation that are appropriate for MEF patients. This approach may help IVF clinics to be better prepared for delivering top-quality care to mostly young, single women facing the daunting prospect of fertility loss and life-threatening medical diagnoses.

Pregnancy outcomes in oocyte recipients with fibroids not impinging uterine cavity.

OBJECTIVE: To examine the effects of fibroid uterus on pregnancy outcomes and endometrial features in ovum donation recipients. METHODS: Retrospective analysis of 744 ovum donation cycles was conducted in two private IVF centers between 2005 and 2012. All the recipients underwent transvaginal ultrasound examination, including endometrial thickness and grade measurements. Clinical pregnancy, spontaneous miscarriage, and live birth rates were regarded as the primary outcomes. RESULTS: Leimyomas not distorting the uterine cavity were diagnosed in 264 (35.5%) of the cycles. This group exhibited lower endometrial thickness (8.33 ± 1.8 vs. 8.73 ± 2.03 mm, p = 0.009), lower rates of Grade A (16.1 vs. 30.1%, p < 0.0001), and higher rates of grade C endometrium (10.2 vs. 5.5%, p < 0.0001), compared to the group with sonographically normal uterine cavity. In addition, significantly higher spontaneous miscarriage rates were found in fibroid uteri group (25 vs. 14.5%, p = 0.036). CONCLUSION: Our study results suggest that uterine fibroids not distorting the uterine cavity could constitute a risk factor for spontaneous miscarriage in oocyte donation cycles, possibly via their adverse effect on endometrial receptivity. Further well-designed trials should widely explore this subject, particularly focusing on impact of myomectomy on fertility rates in these patients.

p27 and its ubiquitin ligase Skp2 expression in endometrium of IVF patients with repeated hormonal stimulation.

This preliminary study examined a possible effect of long duration repeated hormonal stimulation on the endometrium using a molecular tool. The expression of the hormone stimulated, cell cycle regulators, p27 and its ligase S-phase kinase-interacting protein2 (Skp2), were assessed in 46 endometrial samples of patients who underwent repeated IVF cycles (3-21). Skp2 protein is usually undetectable in normal tissue and can be demonstrated only in rapidly dividing cells. Samples from non-stimulated, normal cycling women served as control group A. Samples of endometrial carcinoma served as control group B. In secretory endometrium, the expression of p27 was found to be lower and Skp2 higher in the study group compared with control group A. Moreover, in 25% of patients of the study group, Skp2 expression was significantly higher (P < 0.05) compared with control group A, reaching concentrations demonstrated in endometrial carcinoma. The findings of this study suggest that repeated hormone stimulation cycles may disrupt endometrial physiology, potentially towards abnormal proliferation. These changes in protein expression are described for the first time in IVF patients and should be further investigated.

Oxidative markers in cryopreservation medium from frozen-thawed embryos: a possible tool for improved embryo selection in in vitro fertilization?

PURPOSE: The present study evaluated the association between oxidative parameters in embryo cryopreservation medium and laboratory and clinical outcomes. METHODS: This prospective laboratory study was conducted in an IVF unit in a university-affiliated hospital with 91 IVF patients undergoing a frozen-thawed embryo transfer cycle. Following thawing, 50 µL of embryo cryopreservation medium was retrieved from each cryotube and tested by the thermochemiluminescence (TCL) assay. TCL amplitudes after 50 (H1), 150 (H2), and 280 s (H3) were recorded in counts per second (CPS) and the TCL ratio determined for comparison with implantation and pregnancy rates. RESULTS: A total of 194 embryos were transferred in 85 frozen-thaw cycles. Twenty-one pregnancies (24.7 %) occurred. Implantation and overall and clinical pregnancy rates were higher when the median TCL H1 amplitude was <32 CPS compared to ≥32 CPS (14.6 vs. 5.3 %, 37.5 vs. 17 %, 28.1 vs. 9.4 %, respectively). No pregnancies occurred when the H1 amplitude was ≥40 CPS. Logistic regression multivariate analysis found that only the median TCL H1 amplitude was associated with the occurrence of pregnancy (OR = 2.93, 95 % CI 1.065-8.08). The TCL ratio inversely correlated with the duration of embryo cryopreservation (r = -0.37). CONCLUSIONS: The results indicate that thawed embryos may express oxidative processes in the cryopreservation medium, and higher oxidative levels are associated with lower implantation rates. These findings may aid in the improved selection of frozen-thawed embryos for IVF.

Habits of cell phone usage and sperm quality - does it warrant attention?

Male infertility constitutes 30-40% of all infertility cases. Some studies have shown a continuous decline in semen quality since the beginning of the 20th century. One postulated contributing factor is radio frequency electromagnetic radiation emitted from cell phones. This study investigates an association between characteristics of cell phone usage and semen quality. Questionnaires accessing demographic data and characteristics of cell phone usage were completed by 106 men referred for semen analysis. Results were analysed according to WHO 2010 criteria. Talking for ≥1 h/day and during device charging were associated with higher rates of abnormal semen concentration (60.9% versus 35.7%, P < 0.04 and 66.7% versus 35.6%, P < 0.02, respectively). Among men who reported holding their phones ≤50 cm from the groin, a non-significantly higher rate of abnormal sperm concentration was found (47.1% versus 11.1%). Multivariate analysis revealed that talking while charging the device and smoking were risk factors for abnormal sperm concentration (OR = 4.13 [95% CI 1.28-13.3], P < 0.018 and OR = 3.04 [95% CI 1.14-8.13], P < 0.027, respectively). Our findings suggest that certain aspects of cell phone usage may bear adverse effects on sperm concentration. Investigation using large-scale studies is thus needed.

[CHALLENGING THE OPTIMAL NUMBER OF RETRIEVED OOCYTES AND ITS IMPACT ON PREGNANCY AND LIVE BIRTH RATES IN IVF/ICSI CYCLES].

INTRODUCTION: Large numbers of retrieved oocytes are associated with higher chances of having cryopreservation of embryos. However, the process entailed exposes women to increased risk for ovarian hyperstimulation syndrome. Furthermore, mild ovary stimulation protocols are more patient-friendly and with less adverse effects. Only limited reports exist on the significance of the number of retrieved oocytes achieved in a single stimulation cycle. AIM: To investigate the optimal number of retrieved oocytes to achieve pregnancy and live birth. METHODS: This retrospective analysis included 1590 IVF cycles. Oocytes maturation, fertilization, cleavage, as well as pregnancy and live birth rates were analyzed according to the number of retrieved oocytes. RESULTS: Oocyte maturation, fertilization and cleavage rates were lower in cycles with more than 10 retrieved oocytes compared with other groups. Live birth rates were highest when the number of retrieved oocytes was 11-15. CONCLUSIONS: Retrieval of more than 15 oocytes was not associated with a significant increase in chances of conception and birth. DISCUSSION: The better oocyte quality with 10 or less oocytes retrieved could be the result of a possible interference with the natural selection, or the minimized exposure of growing follicles to the potentially negative effects of ovarian stimulation. Although the average number of available embryos was higher when more than 10 oocytes were retrieved, achievement of more than 15 oocytes did not improve IVF outcome in terms of pregnancy and delivery rates. SUMMARY: Analysis of 1590 IVF cycles including the frozen-thawed transfers shows that the best outcomes were achieved with an optimal number of 11-15 oocytes.

Effects of treatment of ectopic pregnancy with methotrexate or salpingectomy in the subsequent IVF cycle.

Ectopic pregnancy is a known risk for patients treated with IVF. The objective of this study was to evaluate the effect of methotrexate (MTX) and laparoscopic salpingectomy as treatments of ectopic pregnancy on ovarian response during IVF cycles. Data of all women treated for ectopic pregnancy as a result of IVF treatment were evaluated; the study included women who had an unruptured ectopic pregnancy after IVF treatment that was treated with either MTX or laparoscopic salpingectomy and underwent a subsequent IVF cycle. The main outcome measures were baseline serum FSH concentrations and ovarian response in the subsequent IVF cycle after treatment of ectopic pregnancy. Of a total of 58 patients, 36 were previously treated with MTX and 22 others by salpingectomy. No significant differences were observed between the MTX and the salpingectomy groups in the parameters of ovarian response in the subsequent IVF cycle.

[Oxidation and female reproduction: the good, the bad and what's between].

Reactive oxygen and nitrogen species constitute an inseparable part of aerobic life on earth. They have been known to science for about 90 years, but only during the last 50 years research in this field has expanded. Initially, scientists focused on the free radicals-induced damage to biological systems. Since the eighties, a new concept has emerged, namely, that alongside the oxidative stress-induced deleterious effect and its association with a variety of diseases, a certain threshold level of oxidation is essential to intracellular signaL transduction. Recently, some data has accumulated regarding the involvement of oxidative processes in various aspects of female reproduction, including ovarian function, fertilization, early development of the embryo and implantation. Nevertheless, there is still a long way before comprehensive and thorough understanding of their role, both at the molecular level and the expression in the clinical setup of fertility patients can be achieved. In this article, we shall address some molecular biochemical processes involved in the activity of free radicals, and review the present knowledge regarding their role in female fertility, including ovarian physiology, follicular and oocyte maturation, development of the early embryo and implantation, as well as their association with reproductive pathologies such as endometriosis, polycystic ovary disease and recurrent pregnancy loss.

Improving embryo selection by the development of a laboratory-adapted time-lapse model.

OBJECTIVE: To study whether a powerful, in-house, embryo-selection model can be developed for a specific in vitro fertilization (IVF) laboratory where embryos were already selected for transfer using general models. DESIGN: In total, 12,944 fertilized oocytes were incubated in an EmbryoScope (Vitrolife, Göteborg, Sweden) at our laboratory. Embryos were selected for transfer or freezing using general models. There were 1,879 embryos with known implantation data (KID), of which 425 had positive KIDs. For the outcome, we set 3 endpoints for KID's definition: gestational sac, clinical pregnancy, and live birth. Results of a comparison between KID-positive and -negative embryos for cell division timings were analyzed separately for intracytoplasmic sperm injection (ICSI) and IVF embryos in patients aged 18-41 years. SETTING: IVF center. PATIENTS: The study included 1,075 women undergoing IVF or ICSI treatment between June 2013 and February 2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The KID-positive and -negative embryos were analyzed for statistical differences in cell division timing and cell cycle intervals. We used the EmbryoScope Stats software (Unisense FertiliTech, Aarhus, Denmark) for model development. The statistically different timing parameters were tested for their contribution to scoring in the model. The algorithms were tested for area under the receiver operating characteristic curve (AUC) in the KID embryos for developing day-2, -3, and -5 embryo-selection models. The validation of these algorithms was performed using calibration/validation procedures. RESULTS: Because significant differences in morphokinetics were found between the KID-positive and KID-negative embryos in our laboratory, it was possible to use our specific KID data to develop an in-house model. The algorithms were developed for embryo selection on days 2, 3, and 5 in the ICSI embryos. In most cases, AUC was >0.65, which indicated that these models were valid in our laboratory. In addition, these AUC values were obtained from all gestational sac, clinical pregnancy, and live birth KID embryo databases tested. An increase in the predictability of the models was observed from days 2-3 to day 5 models. The AUC test results ranged between 0.657 and 0.673 for day 2 and day 3, respectively, and 0.803 for the day 5 model. CONCLUSION: A model based on laboratory-specific morphokinetics was found to be complementary to general models and an important additive tool for improving single embryo selection. Developing an in-house laboratory-specific model requires many stages of sorting and characterization. Many insights were drawn about the model developing process. These may facilitate and improve the process in other laboratories.

Comparison of day 2 and overnight day 3 frozen embryo transfers: A prospective randomized controlled trial.

In certain patients cleavage stage embryos may be preferred. The relationship between an additional day in culture and pregnancy outcomes is not well established. We aimed to compare outcomes of day 2 versus overnight day 3 frozen embryo transfer (FET). In this randomized controlled trial, patients with day 2 cryopreserved embryos were allocated to two groups. In group A embryos were transferred on day 2, the same day of thawing. In group B embryos were transferred one day after thawing, on day 3 after overnight incubation. Out of 410 patients eligible, 92 were recruited. Finally, 72 patients participated, 39 in group A and 33 in group B. No significant difference in implantation (11 % in group A and 14 % in group B, p = 0.81), clinical pregnancy (18 % in group A and 21 % in group B, p = 0.73) or live birth rates (13 % in group A and 18 % in group B, p = 0.53) was found. To conclude, no significant difference in reproductive outcomes was found when comparing patients with day 2 or overnight day 3 FET. Considering published data on blastocyst transfer, cleavage stage ET may still be a relevant option and the decision between day 2 or overnight day 3 ET depends on patients' and physicians' preference and recommendation.

Quality of life and fertility preservation counseling for women with gynecological cancer: an integrated psychological and clinical perspective.

Purpose: Relational and sexual problems are frequent in patients with a diagnosis of gynecological cancer, because this disease has a strong negative impact on female identity and sexuality. Psychological and sexual functioning is affected by inauspicious diagnosis. Furthermore, therapies may compromise reproductive function. The aim of this study is to propose a general overview on the impact of gynecological cancer on quality of life and psychological and sexual functioning, as well as on the importance of adequate counseling related to fertility preservation techniques.Materials and methods: We provide a narrative overview of the recent literature about quality of life and fertility preservation counselling in women with gynecological cancer.Results and conclusions: According to recent studies, 75% of women between 18 and 45 years with a diagnosis of cancer wish to have children. When cancer affects the reproductive system, the psychological distress is even stronger because there is a loss of menstrual function and fertility. Currently, fertility preservation techniques in women with gynecological cancer are beneficial and lead to an improvement in the quality of life.

The impact of intentional endometrial injury on reproductive outcomes: a systematic review and meta-analysis.

BACKGROUND: Endometrial injury is an intentional damage made to the endometrium, usually produced by a Pipelle catheter. Over the last two decades, endometrial injury has been studied to improve implantation rates and decrease the incidence of implantation failure in invitro fertilization (IVF) cycles. Recently, additional studies of endometrial injury, performed not only in patients with implantation failure but also in intrauterine insemination cycles, have been conducted, and the endometrial injury made by hysteroscopy has been researched. The evidence describing the impact of endometrial injury is controversial; therefore, we conducted a systematic review and meta-analysis to examine the issue. OBJECTIVE AND RATIONALE: Our objective is to review the research that has been done until now and perform a meta-analysis regarding endometrial injury and its influence on implantation success and pregnancy rates in patients with at least one failed IVF cycle. In particular, we aim to study the efficacy of the procedure and look for confounding factors, such as maternal age, in assessing the efficacy of endometrial injury. SEARCH METHODS: The systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Study protocol can be assessed at PROSPERO International prospective register of systematic reviews (registration number CRD42018092773). Searches were conducted by an experienced research librarian in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science and Cochrane Library. This review considered for inclusion randomized-controlled trials examining the success of performing local endometrial injury on IVF outcomes in women with previous failed IVF cycles. OUTCOMES: Ten studies, comprising a total of 1260 patients, were selected. Overall, when studying the effect of endometrial injury on clinical pregnancy rates (CPRs) and live birth rates (LBRs), higher rates were shown in the endometrial injury group. However, endometrial injury did not significantly improve CPRs and LBRs, when considering sub-group analyses of studies including patients with two or more failed IVF cycles, studies examining older patients or studies which did not include hysteroscopy. There was no significant difference found regarding multiple pregnancy rates, while a handful of studies showed an improvement in miscarriage rates. WIDER IMPLICATIONS: Endometrial injury should be used restrictively and not routinely in clinics. Maternal age and number of previous failed treatment cycles may be contributing factors which can influence the results when studying the effect of endometrial local injury. It is possible that the relative contribution of endometrial receptivity to the chances of implantation decreases with any additional failed cycle. The optimal study to prove the efficacy of local endometrial injury on implantation and pregnancy rates, should be a random-controlled trial studying the effect of local endometrial injury in oocyte donation cycles, in recipients with repeated implantation failure. This kind of study will conclude whether local endometrial injury is an efficient procedure with minimum confounding factors, and may assist in defining the population, even outside of donation cycles, that will benefit from the procedure.

In vitro fertilisation policy in Israel and women's perspectives: the more the better?

Israel offers nearly full funding for in vitro fertilisation (IVF) to any Israeli woman irrespective of her marital status or sexual orientation, until she has two children with her current partner. Consequently, Israeli women are the world's most intensive consumers of IVF. This 2006 study explored the perceptions of Israeli IVF patients about the treatment and their experiences, probing possible links between state policy and women's choices and health. Israeli women (n=137), all currently undergoing IVF, were invited to fill out questionnaires. The questionnaires were delivered in five IVF centres by university nursing students or by the clinics' nurses. Most women were optimistic they would become pregnant, and described the treatment as having modest or no negative effects on their lives. They expressed a sweeping commitment to IVF, which they were willing to repeat "as many times as needed". At the same time, the majority appeared to have very partial treatment-related knowledge and marginalised side effects, even though they had experienced some themselves. We interpret the observed favourable image of IVF as closely related to the encouragement implied in the extensive state funding of IVF and in the Jewish Israeli tradition of pronatalism, which may account for the virtual absence of critical public debate on the subject.

Medical egg freezing: How cost and lack of insurance cover impact women and their families.

Medical egg freezing (MEF) is being recommended increasingly for women at risk of losing their reproductive ability due to cancer chemotherapy or other fertility-threatening medical conditions. This first, binational, ethnographic study of women who had undergone MEF sought to explore women's experiences under two different funding systems: (i) the USA, where the cost of MEF is rarely covered by private or state health insurance; and (ii) Israel, where the cost of MEF is covered by national health insurance. Women were recruited from four American and two Israeli in-vitro fertilization clinics where MEF is offered. In-depth, semi-structured interviews were conducted with 45 women (33 Americans, 12 Israelis) who had completed at least one cycle of MEF. All of the Israeli women had cancer diagnoses, but were not faced with the additional burden of funding an MEF cycle. In marked contrast, the American women - 23 with cancer diagnoses and 10 with other fertility-threatening medical conditions - struggled, along with their families, to 'piece together' MEF funding, which added significant financial pressure to an already stressful situation. Given the high priority that both American and Israeli women in this study placed on survival and future motherhood, it is suggested that insurance funding for MEF should be mandated in the USA, as it is in Israel. This article concludes by describing new state legislative efforts in this regard.

The Effect of Paternal Age on Oocyte Donation Outcomes.

IMPORTANCE: In recent decades, a trend toward delayed childbearing is noted in developed countries. Whereas the effects of maternal age on fertility, pregnancy complications, and postnatal outcomes have been thoroughly explored, consequences of advanced paternal age are less well known. Oocyte donation cycles can be used as an optimal model to analyze the association between male ageing and reproductive outcomes with minimal confounding. OBJECTIVE: The purpose of this work was to summarize the updated and relevant literature dealing with the effect of paternal age on oocyte donation outcomes. RESULTS: According to the available evidence from oocyte donation cycles, it seems that no significant association exists between advanced paternal age and fertility. However, this evidence is based on few studies, many of which are of low quality, yielding conflicting results. In addition, the emerging evidence clearly indicates an increased risk of adverse postnatal manifestations of pregnancies conceived by older fathers, including de novo autosomal dominant disorders, impaired neurocognitive development, and increased risk of malignancy. CONCLUSIONS AND RELEVANCE: This review may be of aid to medical practitioners in counseling couples on the risks of delayed childbearing.