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Human Reproduction Current Issue





Published: Wed, 29 Nov 2017 00:00:00 GMT

Last Build Date: Mon, 18 Dec 2017 07:48:07 GMT

 



Conservative surgery versus colorectal resection in deep endometriosis infiltrating the rectum: a randomized trial

Wed, 29 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONIs there a difference in functional outcome between conservative versus radical rectal surgery in patients with large deep endometriosis infiltrating the rectum 2 years postoperatively?SUMMARY ANSWERNo evidence was found that functional outcomes differed when conservative surgery was compared to radical rectal surgery for deeply invasive endometriosis involving the bowel.WHAT IS KNOWN ALREADYAdopting a conservative approach to the surgical management of deep endometriosis infiltrating the rectum, by employing shaving or disc excision, appears to yield improved digestive functional outcomes. However, previous comparative studies were not randomized, introducing a possible bias regarding the presumed superiority of conservative techniques due to the inclusion of patients with more severe deep endometriosis who underwent colorectal resection.STUDY DESIGN SIZE, DURATIONFrom March 2011 to August 2013, we performed a 2-arm randomized trial, enroling 60 patients with deep endometriosis infiltrating the rectum up to 15 cm from the anus, measuring more than 20 mm in length, involving at least the muscular layer in depth and up to 50% of rectal circumference. No women were lost to follow-up.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients were enroled in three French university hospitals and had either conservative surgery, by shaving or disc excision, or radical rectal surgery, by segmental resection. Randomization was performed preoperatively using sequentially numbered, opaque, sealed envelopes, and patients were informed of the results of randomization. The primary endpoint was the proportion of patients experiencing one of the following symptoms: constipation (1 stool/>5 consecutive days), frequent bowel movements (≥3 stools/day), defecation pain, anal incontinence, dysuria or bladder atony requiring self-catheterization 24 months postoperatively. Secondary endpoints were the values of the Visual Analog Scale (VAS), Knowles–Eccersley–Scott-Symptom Questionnaire (KESS), the Gastrointestinal Quality of Life Index (GIQLI), the Wexner scale, the Urinary Symptom Profile (USP) and the Short Form 36 Health Survey (SF36).MAIN RESULTS AND THE ROLE OF CHANCEA total of 60 patients were enroled. Among the 27 patients in the conservative surgery arm, two were converted to segmental resection (7.4%). In each group, 13 presented with at least one functional problem at 24 months after surgery (48.1 versus 39.4%, OR = 0.70, 95% CI 0.22–2.21). The intention-to-treat comparison of the overall scores on KESS, GIQLI, Wexner, USP and SF36 did not reveal significant differences between the two arms. Segmental resection was associated with a significant risk of bowel stenosis.LIMITATIONS REASONS FOR CAUTIONThe inclusion of only large infiltrations of the rectum does not allow the extrapolation of conclusions to small nodules of <20 mm in length. The presumption of a 40% difference favourable to conservative surgery in terms of postoperative functional outcomes resulted in a lack of power to demonstrate a difference for the primary endpoint.WIDER IMPLICATIONS OF THE FINDINGSConservative surgery is feasible in patients managed for large deep rectal endometriosis. The trial does not show a statistically significant superiority of conservative surgery for mid-term functional digestive and urinary outcomes in this specific population of women with large involvement of the rectum. There is a higher risk of rectal stenosis after segmental resection, requiring additional endoscopic or surgical procedures.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by a grant from the clinical research programme for hospitals (PHRC) in France. The authors declare no competing interests related to this study.TRIAL REGISTRATION NUMBERThis study is registered with ClinicalTrials.gov, number NCT 01291576.TRIAL REGISTRATION DATE31 January 2011.DATE OF FIRST PATIENT’S ENROLMENT7 March 2011.[...]



Chronic hyperandrogenemia in the presence and absence of a western-style diet impairs ovarian and uterine structure/function in young adult rhesus monkeys

Tue, 28 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONDoes chronic hyperandrogenemia beginning at menarche, in the absence and presence of a western-style diet (WSD), alter ovarian and uterine structure-function in young adult rhesus monkeys?SUMMARY ANSWERPhenotypic alterations in ovarian and uterine structure/function were induced by exogenous testosterone (T), and compounded in the presence of a WSD (T+WSD).WHAT IS KNOWN ALREADYHyperandrogenemia is a well-established component of PCOS and is observed in adolescent girls, indicating a potential pubertal onset of disease symptoms. Obesity is often associated with hyperandrogenemia and it is hypothesized that metabolic dysfunction exacerbates PCOS symptoms.STUDY DESIGN, SIZE, DURATIONMacaque females (n = 40) near the onset of menarche (~2.5 years of age) were assigned to a 2 by 2 factorial cohort design. Effects on reproductive characteristics were evaluated after 3 years of treatment.PARTICIPANTS/MATERIALS, SETTING, METHODSRhesus macaques (Macaca mulatta) were fed either a normal balanced diet (n = 20) or a WSD (n = 20). Additionally, implants containing cholesterol (n = 20) or T (n = 20) were implanted subcutaneously to elevate serum T approximately 5-fold. This resulted in treatment groups of controls (C), T, WSD and T+WSD (n = 10/group). Vaginal swabbing was performed daily to detect menses. After 3 years of treatment, daily serum samples from one menstrual cycle were assayed for hormone levels. Ovarian structure was evaluated in the early follicular phase by 3D/4D ultrasound. Uterine endometrial size and ovarian/luteal vascular function was also evaluated in subgroups (n = 6/group) in the late follicular and mid-luteal phases by 3D/4D ultrasound and contrast-enhanced ultrasound, respectively. Expression of steroid hormone receptors and markers of decidualization and endometrial receptivity were assessed in endometrial biopsies at mid-luteal phase.MAIN RESULTS AND THE ROLE OF CHANCEApproximately 90% of menstrual cycles appeared ovulatory with no differences in frequency or duration between groups. Serum estradiol (E2) levels during the early follicular phase were greatest in the T alone group, but reduced in T+WSD (P < 0.02). Serum LH was elevated in the T group (P < 0.04); however, there were no differences among groups in FSH levels (P > 0.13). Ovarian size at menses tended to be greater in the WSD groups (P < 0.07) and antral follicles ≥1 mm were more numerous in the T+WSD group (P < 0.05). Also, females in T and T+WSD groups displayed polycystic ovarian morphology (PCOM) at greater frequency than C or WSD groups (P < 0.01). Progesterone (P4) levels during the luteal phase were reduced in the T+WSD group compared to C and T groups (P < 0.05). Blood volume (BV) and vascular flow (VF) within the corpus luteum was reduced in all treatment groups compared to C (P < 0.01, P = 0.03), with the WSD alone group displaying the slowest BV and VF (P < 0.05). C and WSD groups displayed endometrial glands at mid-luteal phase with low estrogen receptor 1 (ESR1) and progesterone receptor (PGR) mRNA and immunohistochemical staining in the functionalis zone, but appreciable PGR in the stroma. In contrast, T and T+WSD treatment resulted in glands with less secretory morphology, high ESR1 expression in the glandular epithelium and low PGR in the stroma. Endometrial levels of TIMP3 and MMP26 mRNA and immunostaining were also decreased in the T and T+WSD groups, whereas AR expression was unchanged.LARGE SCALE DATANone.LIMITATIONS, REASONS FOR CAUTIONFemales are young adults, so effects could change as they reach prime reproductive age. The T level generated for hyperandrogenemia may be somewhat greater than the 3–4-fold increase observed in adolescent girls, but markedly less than those observed in male monkeys or adolescent boys.WIDER IMPLICATIONS OF THE FINDINGSAlterations to ovarian and uterine structure-function observed in T and, in particular, T+WSD-treated female macaques are consistent with some of the features observed in women diagnosed with polycyst[...]



Broad support for regulating the clinical implementation of future reproductive techniques

Tue, 28 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONDo gynaecologists, infertile patients and the general public, consider that regulation of the clinical implementation of stem cell-based fertility treatments is required?SUMMARY ANSWERThere is broad support from gynaecologists, patients and the general public for regulating the clinical implementation of future stem cell-based fertility treatments.WHAT IS KNOWN ALREADYThere is debate on the need to regulate the clinical implementation of novel techniques. Regulation may hinder their swift adoption and delay benefits for patients, but may prevent the implementation of ineffective or harmful techniques. Stem cell-based fertility treatments, which involve creating oocytes or spermatozoa by manipulating stem cells, are likely to be implemented in clinical practice in the near future and will probably impact future generations as well as the current one.STUDY DESIGN, SIZE, DURATIONA cross-sectional survey was conducted among gynaecologists working in fertility clinics (n = 179), patients with severe infertility (n = 348) and a representative sample of the general public (n = 1250). The questionnaire was disseminated in the Netherlands in the winter of 2015–2016.PARTICIPANTS/MATERIALS, SETTING, METHODSThe newly developed questionnaire was reviewed by experts and tested among the general public. The questionnaire assessed whether participants wanted each of nine potential negative consequences of the clinical implementation of stem cell-based fertility treatments to be regulated. In addition, the importance of all negative and positive potential consequences, the appropriate regulatory body and its need to consult with advisors from various backgrounds was questioned.MAIN RESULTS AND THE ROLE OF CHANCEIn total, 958 respondents completed the questionnaire (response rate: 54%). A large majority of each participant group (>85%) wanted regulation, for at least one potential negative consequence of the clinical implementation of stem cell-based fertility treatments. The majority of all participant groups wanted regulation for serious health risks for intended parents, serious health risks for children and the disposal of human embryos. Regulation for out-of-pocket costs and the burden of treatment received little support. The majority of gynaecologists and the general public, but not the patients, requested regulation for the risk of minor congenital abnormalities, the success rates and the naturalness of treatments. Nevertheless, the majority of patients did consider the former two potential negative consequences important. The majority of all groups preferred a national bioethics committee as the regulatory body. This committee should consult with advisors from various backgrounds and should consider the broader context of potential consequences of the stem cell-based fertility treatments.LIMITATIONS, REASONS FOR CAUTIONThis empirical study focuses on only three stakeholder groups. This study reports on the perspective of the majority and this is not per definition the morally right perspective. The transferability of our findings to other cultures and other techniques remains unclear.WIDER IMPLICATIONS OF THE FINDINGSA national bioethics committee, consulting with advisors from various backgrounds, should regulate the clinical implementation of future stem cell-based fertility treatments. Whether this broad support for regulation applies to novel techniques from other fields of medicine should be examined.STUDY FUNDING/COMPETING INTEREST(S)The Young Academy of the Royal Netherlands Academy of Arts and Sciences. None of the authors has any conflict of interest to declare.TRIAL REGISTRATION NUMBERNot applicable.[...]



Antenatal paternal adjustment and paternal attitudes after infertility treatment

Fri, 24 Nov 2017 00:00:00 GMT

Abstract
STUDY QUESTION
Do mode of conception [ART versus Natural (NC)] and depression have an interactive effect on antenatal paternal adjustment and paternal attitudes?
SUMMARY ANSWER
Depression increased the negative effect of ART on antenatal paternal adjustment and paternal attitudes, specifically on antenatal marital relationship satisfaction.
WHAT IS KNOWN ALREADY
Research on antenatal paternal adjustment and paternal attitudes after ART is scarce and has produced inconsistent results.
STUDY DESIGN, SIZE, DURATION
This cross-sectional study assessed 197 primiparous men (71 ART and 126 NC) during their partner’s second trimester of gestation.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants were derived from three larger longitudinal studies recruited at public Health Services in Northern Portugal. All men, for who this was their first child and had filled in a socio-demographic questionnaire, measures of depression and anxiety, and antenatal paternal adjustment and paternal attitudes were selected.
MAIN RESULTS AND THE ROLE OF CHANCE
An interaction effect of mode of conception and depression was found on antenatal paternal adjustment and paternal attitudes. ART men showing high depressive symptomatology had lower antenatal marital relationship satisfaction than ART men showing low depressive symptomatology and NC men showing high or low depressive symptomatology.
LIMITATIONS, REASONS FOR CAUTION
Due to the cross-sectional design of this study and the small sample size in the depression groups, the findings should be interpreted with caution.
WIDER IMPLICATIONS OF THE FINDINGS
Specialized psychological support should be available for ART men screened with high depressive symptomatology as part of routine prenatal care appointments.
STUDY FUNDING/COMPETING INTEREST(S)
This study was conducted at Psychology Research Centre (UID/PSI/ 01662/2013), University of Minho, and at the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UID/DTP/04750/2013). It was supported by the Foundation for Science and Technology (Portuguese Ministry of Education and Science) through National funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653) and through the Operational Programme Factors of Competitiveness–COMPETE within the project ‘Health, Governance and Accountability in Embryo Research: Couples’ Decisions About the Fates of Embryos’ (FCOMP-01-0124-FEDER-014453), the FCT Investigator contract IF/01674/2015 and PhD grants (SFRH/BD/115048/2016, SFRH/BD/75807/2011 and SFRH/BD/40146/2007). The authors have no conflicts of interest.



Health-related knowledge, beliefs and self-efficacy in women with polycystic ovary syndrome

Wed, 22 Nov 2017 00:00:00 GMT

Abstract
STUDY QUESTION
Do health-related knowledge, beliefs and self-efficacy differ between women with and without polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Women with PCOS felt at greater risk for adverse health outcomes, yet believed a healthy lifestyle was less beneficial to prevent weight gain relative to a comparison group.
WHAT IS KNOWN ALREADY
Diet and physical activity are often used to treat PCOS, but there are high attrition rates and less engagement in self-help methods. It is unclear whether there are unique psychosocial considerations in PCOS that should be incorporated into these interventions.
STUDY DESIGN, SIZE, DURATION
This cross-sectional study enrolled 475 women with (N = 255) and without PCOS (N = 220).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Female participants were recruited through paper and web-based advertisements across the US (mean age: 28.1 ± 5.4 years). Participants were either diagnosed with PCOS by a healthcare professional (PCOS group) or had self-reported regular menstrual cycles (comparison group). A reliable and valid online instrument about health-related knowledge, beliefs and self-efficacy was administered to these participants.
MAIN RESULTS AND THE ROLE OF CHANCE
Most women with PCOS had a basic understanding of nutrition (96%), but had misconceptions about diagnostic criteria for PCOS (≥86%). PCOS was associated with greater perceived susceptibility for disease and weight gain and poorer perceived control over these health outcomes (all P < 0.05), in relation to the comparison group. Women with PCOS also perceived fewer benefits of healthy behaviors on weight gain (P = 0.03) with less than half of the PCOS group attempting to follow government diet recommendations (47%). There were no differences in the self-efficacy of dietary behaviors between groups.
LIMITATIONS, REASONS FOR CAUTION
It is likely that participant self-selection occurred due to the nature of recruitment in this study and results may have limited generalizability since most participants identified as Caucasian. Additionally, it is unclear whether some results may be clinically meaningful due to small effect sizes.
WIDER IMPLICATIONS OF THE FINDINGS
These findings support that behavioral interventions should incorporate the unique psychosocial considerations associated with PCOS to encourage patient participation in lifestyle interventions.
STUDY FUNDING/COMPETING INTEREST(S)
This manuscript was partially supported by Cornell University Human Ecology Alumni Association and College of Agriculture and Life Sciences Alumni Association. The authors have no competing interests.
TRIAL REGISTRATION NUMBER
NCT01859663






Optimal timing for blastomere biopsy of 8-cell embryos for preimplantation genetic diagnosis

Mon, 20 Nov 2017 00:00:00 GMT

Abstract
STUDY QUESTION
What is the optimal timing for blastomere biopsy during the 8-cell stage, at which embryos will have the best implantation potential?
SUMMARY ANSWER
Fast-cleaving embryos that are biopsied during the last quarter (Q4) of the 8-cell stage and are less affected by the biopsy procedure, and their implantation potential is better than that of embryos biopsied earlier during the 8-cell stage (Q1–Q3).
WHAT IS KNOWN ALREADY
Blastomer biopsy from cleavage-stage embryos is usually performed on the morning of Day 3 when the embryos are at the 6- to 8-cell stage and is still the preferred biopsy method for preimplantation genetic diagnosis (PGD) for monogentic disorders or chromosomal translocations. Human embryos usually remain at the 8-cell stage for a relatively long ‘arrest phase’ in which cells grow, duplicate their DNA and synthesize various proteins in preparation for the subsequent division.
STUDY DESIGN, SIZE, DURATION
This is a retrospective cohort study. The study group (195 embryos) included all 8-cell stage embryos that underwent blastomere biopsy for PGD for monogenetic disorders and chromosomal translocations in our unit between 2012–2014 and cultured in the EmbryoScope until transfer. The control group (115 embryos) included all embryos that underwent intracytoplasmic sperm injection without a biopsy during the same period.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The 8-cell stage was divided into four quarters: the first 5 h post-t8 (Q1), 5–10 h post-t8 (Q2), 10–15 h post-t8 (Q3) and at 15–20 h post-t8 (Q4). Non-biopsied control embryos were divided into four equivalent quarters. Embryos were evaluated for timing of developmental events following biopsy including timing of first cleavge after biopsy, timing of comapction (tM) and start of blastulation (tSB). Timing of these events were compared between PGD and control embryos, as well as with 56 PGD implanted embryos with Known Implantation Data (PGD-KID-positive embryos).
MAIN RESULTS AND THE ROLE OF CHANCE
Embryos that were biopsied during Q3 (10–15 h from entry into 8-cell stage) were delayed in all three subsequent developmental events, including first cleavage after biopsy, compaction and start of blastulation. In contrast, these events occurred exactly at the same time as in the control group, in embryos that were biopsied during Q1, Q2 or Q4 of the 8-cell stage. The results show also that embryos that were biopsied during Q1, Q2 or Q3 of the 8-cell stage demonstrated a significant delay from the biopsied implanted embryos already in t8 as well as in tM and tSB. However, embryos that were biopsied during Q4 demonstrated dynamics similar to those of the biopsied implanted embryos in t8 and tM, and a delay was noticed only in the last stage of tSB.
LIMITATIONS, REASONS FOR CAUTION
This is a retrospective study that is limited to the timing of biopsy that is routinely performed in the IVF lab. A prospective study in which biopsy will be performed at a desired timing is needed in order to differ between the effect of biopsy itself and the cleavage rate of the embryo.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings showed that blastomere biopsy can be less harmful to further development if it is carried out during a critical period of embryonic growth, i.e during Q4 of the 8-cell stage. They also demonstrated the added value of time-lapse microscopy for determining the optimal timing for blastomere biopsy.
STUDY FUNDING/COMPETING INTEREST(S)
The study was funded by the routine budget of our IVF unit.
TRIAL REGISTRATION NUMBER
N/A.



Battling bias

Sat, 18 Nov 2017 00:00:00 GMT




Down-regulation of miR-378a-3p induces decidual cell apoptosis: a possible mechanism for early pregnancy loss

Sat, 18 Nov 2017 00:00:00 GMT

Abstract
STUDY QUESTION
Do microRNAs (miRNAs) contribute to human early pregnancy loss (EPL)?
SUMMARY ANSWER
miR-378a-3p expression is regulated by progesterone and is down-regulated in ducidua of EPL patients which may contribute to decidual apoptosis through Caspase-3 activation.
WHAT IS KNOWN ALREADY
A variety of miRNAs have been demonstrated to be associated with the development of decidualization and placental formation. However, little has been reported on the roles of miRNA in the pathogenesis of EPL.
STUDY DESIGN, SIZE, DURATION
Normal and EPL decidual tissues were collected from patients with normal pregnancies undergoing elective termination of gestation, and from patients with EPL, respectively.
PARTICIPANTS/MATERIALS, SETTING, METHODS
miRNA microarrays were used to identify the differentially expressed miRNAs between normal and EPL decidua, and miRNA expression was confirmed by qRT-PCR, qRT-PCR, western blotting and luciferase reporter assays were employed to validate the downstream targets of miR-378a-3p. The effects of miR-378a-3p were evaluated using miR-378a-3p—transfected decidual cells.
MAIN RESULTS AND THE ROLE OF CHANCE
Of note, 32 up-regulated miRNAs and 38 down-regulated miRNAs were identified by microarray analysis when comparing EPL to normal decidua. MiR-378a-3p was significantly down-regulated in the EPL decidua and was found to inversely regulate the expression of Caspase-3 by directly binding to its 3′-UTRs. In decidual cells, transfection of miR-378a-3p mimics resulted in the inhibition of cell apoptosis and in the increase of cell proliferation through Caspase-3 suppression. Moreover, we found that progesterone could induce the expression of miR-378a-3p in decidual cells.
LIMITATIONS, REASONS FOR CAUTION
This study focused on the function of miR-378a-3p and its target Caspase-3, however, numerous other targets and miRNAs may also be responsible for the pathogenesis of EPL. Therefore, further studies are required to elucidate the role of miRNAs in EPL.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings indicate that miR-378a-3p may contribute to the development of EPL, and that it could serve as a new potential predictive and therapeutic target of progesterone-treatment for EPL.
STUDY FUNDING/COMPETING INTEREST
This study was supported by National Basic Research Program of China (No.2012CB944900); National Science Foundation of China (No.31471405 and 81490742, No.81361120246); The National Science and Technology Support Program (No.2012BA132B00). Authors declare no competing interests.



Long-term health in recipients of transplanted in vitro propagated spermatogonial stem cells

Sat, 18 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONIs testicular transplantation of in vitro propagated spermatogonial stem cells associated with increased cancer incidence and decreased survival rates in recipient mice?SUMMARY ANSWERCancer incidence was not increased and long-term survival rate was not altered after transplantation of in vitro propagated murine spermatogonial stem cells (SSCs) in busulfan-treated recipients as compared to non-transplanted busulfan-treated controls.WHAT IS KNOWN ALREADYSpermatogonial stem cell autotransplantation (SSCT) is a promising experimental reproductive technique currently under development to restore fertility in male childhood cancer survivors. Most preclinical studies have focused on the proof-of-principle of the functionality and efficiency of this technique. The long-term health of recipients of SSCT has not been studied systematically.STUDY DESIGN, SIZE, DURATIONThis study was designed as a murine equivalent of a clinical prospective study design. Long-term follow-up was performed for mice who received a busulfan treatment followed by either an intratesticular transplantation of in vitro propagated enhanced green fluorescent protein (eGFP) positive SSCs (cases, n = 34) or no transplantation (control, n = 37). Using a power calculation, we estimated that 36 animals per group would be sufficient to provide an 80% power and with a 5% level of significance to demonstrate a 25% increase in cancer incidence in the transplanted group. The survival rate and cancer incidence was investigated until the age of 18 months.PARTICIPANTS/MATERIALS, SETTING, METHODSNeonatal male B6D2F1 actin-eGFP transgenic mouse testis were used to initiate eGFP positive germline stem (GS) cell culture, which harbor SSCs. Six-week old male C57BL/6 J mice received a single dose busulfan treatment to deplete the testis from endogenous spermatogenesis. Half of these mice received a testicular transplantation of cultured eGFP positive GS cells, while the remainder of mice served as a control group. Mice were followed up until the age of 18 months (497–517 days post-busulfan) or sacrificed earlier due to severe discomfort or illness. Survival data were collected. To evaluate cancer incidence a necropsy was performed and tissues were collected. eGFP signal in transplanted testis and in benign and malignant lesions was assessed by standard PCR.MAIN RESULTS AND THE ROLE OF CHANCEWe found 9% (95% CI: 2–25%) malignancies in the transplanted busulfan-treated animals compared to 26% (95% CI: 14–45%) in the busulfan-treated control group, indicating no statistically significant difference in incidence of malignant lesions in transplanted and control mice (OR: 0.3, 95% CI: 0.1–1.1). Furthermore, none of the malignancies that arose in the transplanted animals contained eGFP signal, suggesting that they are not derived from the in vitro propagated transplanted SSCs. Mean survival time after busulfan treatment was found to be equal, with a mean survival time for transplanted animals of 478 days and 437 days for control animals (P = 0.076).LARGE SCALE DATANA.LIMITATIONS, REASONS FOR CAUTIONAlthough we attempted to mimic the future clinical application of SSCT in humans as close as possible, the mouse model that we used might not reflect all aspects of the future clinical setting.WIDER IMPLICATIONS OF THE FINDINGSThe absence of an increase in cancer incidence and a decrease in survival of mice that received a testicular transplantation of in vitro propagated SSCs is reassuring in light of the future clinical application of SSCT in humans.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by KiKa (Kika86) and ZonMw (TAS 116003002). The authors report no financial or other conflict of interest relevant to the subject of this article.[...]






Focused time-lapse analysis reveals novel aspects of human fertilization and suggests new parameters of embryo viability

Wed, 15 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONCan focused application of time-lapse microscopy (TLM) lead to a more detailed map of the morphokinetics of human fertilization, revealing novel or neglected aspects of this process?SUMMARY ANSWERIntensive harnessing of TLM reveals novel or previously poorly characterised phenomena of fertilization, such as a cytoplasmic wave (CW) preceding pronuclear formation and kinetics of pronuclear chromatin polarization, thereby suggesting novel non-invasive biomarkers of embryo quality.WHAT IS KNOWN ALREADYIn recent years, human preimplantation development has been the object of TLM studies with the intent to develop morphokinetic algorithms able to predict blastocyst formation and implantation. Regardless, our appreciation of the morphokinetics of fertilization remains rather scarce, currently including only times of polar body II (PBII) emission, pronuclear appearance and fading, and first cleavage. This is not consistent with the complexity and importance of this process, calling for further TLM studies aimed at describing previously unrecognized or undetected morphokinetic events and identifying novel developmental biomarkers.STUDY DESIGN, SIZE, DURATIONThe study involved a retrospective observation by TLM of the fertilization process in 500 oocytes utilized in consecutive ICSI cycles carried out in 2016. A maximum of five fertilized oocytes per patients were included in the analysis to reduce possible patient-specific biases. Oocytes of patients with different diagnoses of infertility where included in the analysis, while cases involving cryopreserved gametes or surgically retrieved sperm were excluded.PARTICIPANTS/MATERIALS, SETTINGS, METHODSMicroinjected oocytes where assessed by a combined TLM-culture system (Embryoscope). Oocytes that were not amenable to TLM assessment, due to excess of residual corona cells or inadequate orientation for the observation of PBII emission, were not analysed. We identified and monitored 28 parameters relevant to meiotic resumption, pronuclear dynamics, chromatin organization, and cytoplasmic/cortical modifications. Times (T) were expressed as mean ± SD hours post-insemination (p.i.) and analysed, where appropriate, by Paired T Student or Fisher’s exact tests.MAIN RESULTS AND ROLE OF CHANCEPBII emission was occasionally followed (4.3% of cases) by the transient appearance of a protrusion of the cell surface, the fertilization cone (FC), probably resulting from interaction of the male chromatin with the oocyte cortex.Pronuclear formation was always preceded by a radial CW originating from the initial position of the male pronucleus (PN) and extending towards the oocyte periphery. The appearance of the CW followed a precise sequence, occurring always 2–3 h after PBII emission and shortly before PN appearance.Male and female PN appeared virtually simultaneously at approximately 6.2 h p.i. However, while the female PN always formed cortically and near the site of emission of the PBII, the initial position of the male PN was cortical, intermediate, or central (15.2%, 31.2% and 53.6%, respectively). PN juxtaposition involved rapid and straight movement of the female PN towards the male PN. In addition, the initial position of male PN formation was predictive of the position of PN juxtaposition. It was also observed that nucleolar precursor bodies (NPBs) aligned along the juxtaposition area and this happened considerably earlier for the female PN (8.2 ± 2.6 vs.11.2 ± 4.1 h, P = 0.0001).Although it occurred rarely, displacement of juxtaposed PN to the cortex was strongly associated (P < 0.0001) with direct cleavage into three blastomeres at the first cell division. The times of PN breakdown and first cleavage showed a very consistent trend, occurring earlier or progressiv[...]



Wellbeing of gay fathers with children born through surrogacy: a comparison with lesbian-mother families and heterosexual IVF parent families

Tue, 14 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONAre there differences in levels of parental wellbeing (parental stress, psychological adjustment and partner relationship satisfaction) between gay-father families with infants born through surrogacy, lesbian-mother families with infants born through donor insemination, and heterosexual-parent families with infants born through IVF?SUMMARY ANSWERThere were no differences in parental wellbeing.WHAT IS KNOWN ALREADYThe only other study of parental wellbeing in gay-father families formed through surrogacy (mean age children: 4 years old) found no difference in couple relationship satisfaction between these families and lesbian-mother families formed through donor insemination and heterosexual-parent families formed without assisted reproductive technologies.STUDY DESIGN, SIZE, DURATIONThis cross-sectional study is part of an international research project involving 38 gay-father families, 61 lesbian-mother families and 41 heterosexual-parent families with 4-month-olds. In each country (the UK, the Netherlands and France), participants were recruited through several sources, such as specialist lawyers with expertise in surrogacy (for the recruitment of gay fathers), lesbian and gay parenting support groups, fertility clinics (for the recruitment of lesbian and heterosexual parents), and/or online forums and magazines.PARTICIPANTS/MATERIALS, SETTING, METHODSDuring a home visit when their infants were between 3.5 and 4.5 months old, participants completed standardized measures of parental stress, parental psychological adjustment (anxiety and depression) and partner relationship satisfaction.MAIN RESULTS AND THE ROLE OF CHANCEAll parents reported relatively low levels of parental stress, anxiety and depression, and were all relatively satisfied with their intimate relationships. After controlling for caregiver role (primary or secondary caregiver role), there were no significant family type differences in parental stress, P = 0.949, depression, P = 0.089, anxiety, P = 0.117, or relationship satisfaction, P = 0.354.LIMITATIONS, REASONS FOR CAUTIONThe findings cannot be generalized to all first-time ART parents with infants because only families from relatively privileged backgrounds participated.WIDER IMPLICATIONS OF THE FINDINGSOur findings may have implications for the development of policy and legislation in relation to these new family forms, as well as the regulation of surrogacy in the Netherlands and France. In addition, our findings might encourage professional organizations of obstetricians and gynecologists in these countries to recommend that requests for assisted reproduction should be considered regardless of the applicants’ sexual orientation.STUDY FUNDING/COMPETING INTEREST(S)This research was supported, under the auspices of the Open Research Area (Application BO 3973/1-1; Principal Investigator, Michael E Lamb), by grants from the UK Economic and Social Research Council (ESRC; Grant ES/K006150/1; Principal Investigator, Michael E. Lamb), The Netherlands Organisation for Scientific Research (NWO; Grant NWO 464-11-001, Principal Investigator, Henny W.M. Bos) and the French Agence Nationale de Recherche (ANR; Grant ANR-12-ORAR-00005-01, Principal Investigator, Olivier Vecho) whose support is gratefully acknowledged. There were no competing interests.[...]



Waddlia chondrophila, a Chlamydia-related bacterium, has a negative impact on human spermatozoa

Tue, 14 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONWhat is the impact of Waddlia chondrophila, an emerging Chlamydia-related bacterium associated with miscarriage, on human spermatozoa?SUMMARY ANSWERW. chondrophila had a negative impact on human spermatozoa (decrease in viability and mitochondrial membrane potential) and was not entirely removed from infected samples by density gradient centrifugation.WHAT IS KNOWN ALREADYBacterial infection or colonization might have a deleterious effect on male fertility. Waddlia chondrophila was previously associated with miscarriage, but its impact on male reproductive function has never been studied.STUDY DESIGN SIZE, DURATIONAn in vitro model of human spermatozoa infection was used to assess the effects of W. chondrophila infection. Controls included Chlamydia trachomatis serovar D and latex beads with similar size to bacteria.PARTICIPANTS/MATERIALS, SETTING, METHODSPurified motile spermatozoa were infected with W. chondrophila (multiplicity of infection of 1). Immunohistochemistry combined with confocal microscopy was used to evaluate how bacteria interact with spermatozoa. The impact on physiology was assessed by monitoring cell viability, mitochondrial membrane potential and DNA fragmentation.MAIN RESULTS AND THE ROLE OF CHANCEUsing super-resolution confocal microscopy, bacteria were localized on spermatozoa surface, as well as inside the cytoplasm. Compared to controls, W. chondrophila caused a 20% increase in mortality over 72 h of incubation (P < 0.05). Moreover, higher bacterial loads significantly reduced mitochondrial membrane potential. Bacteria present on spermatozoa surface were able to further infect a cell-monolayer, indicating that sperm might vector bacteria during sexual intercourse.LIMITATIONS REASONS FOR CAUTIONThe main limitation of the study is the use of an in vitro model of infection, which might be too simplistic compared to an actual infection. An animal model of infection should be developed to better evaluate the in vivo impact of W. chondrophila.WIDER IMPLICATIONS OF THE FINDINGSIntracellular bacteria, including C. trachomatis, Mycoplasma spp. and Ureaplasma spp., are associated with male infertility. Waddlia chondrophila might represent yet another member of this group, highlighting the need for more rigorous microbiological analysis during investigations for male infertility.STUDY FUNDING/COMPETING INTEREST(S)This work has been funded by the Department of Obstetrics and Gynecology, Lausanne University Hospital, Switzerland, and by the Swiss National Science Foundation (Grant nos. 310030-156169/1, 320030-169853/1 and 320030-169853/2 attributed to D.B.). D.B. is also supported by the ‘Fondation Leenaards’ through the ‘Bourse pour la relève académique’, by the ‘Fondation Divesa’ and by the ‘Loterie Romande’. No conflicts of interest to declare.[...]



Developmental outcome of 9-year-old children born after PGS: follow-up of a randomized trial

Fri, 10 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONDoes Day-3 cleavage-stage PGS affect neurodevelopment of 9-year-old IVF offspring?SUMMARY ANSWERWe did not find evidence of adverse consequences of Day-3 cleavage-stage PGS on neurodevelopment of 9-year-old IVF offspring, although children born after IVF with or without PGS often had a non-optimal neurological condition.WHAT IS KNOWN ALREADYKnowledge on long-term sequelae for development and health of children born following PGS is lacking. This is striking as evidence accumulates that IVF itself is associated with increased risk for impaired health and development in the offspring.STUDY DESIGN SIZE, DURATIONThis prospective, assessor-blinded, multicentre, follow-up study evaluated development and health of 9-year-old IVF children born to women who were randomly assigned to IVF with PGS (PGS group) or without PGS (control group). The follow-up examination at 9 years took place between March 2014 and May 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSIn total, 408 women were included and randomly assigned to IVF with or without Day-3 cleavage-stage PGS. This resulted in 52 ongoing pregnancies in the PGS group and 74 in the control group. In the PGS group, 59 children were born alive; in the control group, 85 children were born alive. At the age of 9 years, 43 children born after PGS and 56 control children participated in the study. Our primary outcome was the neurological optimality score, a sensitive measure of neurological condition assessed with a standardized, age-specific test (Touwen test). Secondary outcomes were adverse neurological condition (neurologically abnormal and the complex form of minor neurological dysfunction), cognitive development (intelligence quotient and specific domains), behaviour (parental and teacher’s questionnaires), blood pressure and anthropometrics.MAIN RESULTS AND THE ROLE OF CHANCENeurodevelopmental outcome of PGS children did not differ from that of controls; the neurological optimality scores (mean values [(95% CI]: PGS children 51.5 [49.3; 53.7], control children 53.1 [50.5; 55.7]) were not significantly different. The prevalences of adverse neurological outcome (in all but one child implying the presence of the complex form of minor neurological dysfunction) did not differ between the groups (PGS group 17/43 [40%], control group 19/56 [34%]), although the prevalence of complex minor neurological dysfunction in both groups was rather high. Also intelligence quotient scores of the two groups were not significantly different (PGS group 114 [108; 120]); control group 117 [109; 125]), and the behaviour, blood pressure and anthropometrics of both groups did not differ. Mean blood pressures of both groups were above the 60th percentile.LIMITATIONS REASONS FOR CAUTIONThe power analysis of the study was not based on the number of children needed for the follow-up study, but on the number of women who were needed to detect an increase in ongoing pregnancy rates after PGS. In addition, our study evaluated embryo biopsy in the form of PGS at cleavage stage (Day-3 embryo biopsy), while currently PGS at blastocyst stage (Day-5 embryo biopsy) is recommended and increasingly being used.WIDER IMPLICATIONS OF THE FINDINGSOur findings indicate that PGS in cleavage stage embryos is not associated with adverse effects on neurological, cognitive and behavioural development, blood pressure and anthropometrics of offspring at 9 years. This is a reassuring finding as embryo biopsy in the forms of PGS and PGD is increasingly applied. However, both groups of IVF offspring showed high prevalences of the clinically relevant form of minor neurological dysfunction, which is a point of concern for the IVF community.[...]



Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction

Fri, 10 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONAre serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes?SUMMARY ANSWERSerum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART.WHAT IS KNOWN ALREADYIntake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART.STUDY DESIGN SIZE, AND DURATIONThis analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection.PARTICIPANTS/MATERIALS, SETTING, METHODSSerum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth.MAIN RESULTS AND ROLE OF CHANCEThe median [25th, 75th percentile] serum level of ω3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ω3-PUFA for 1% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes.LIMITATIONS REASONS FOR CAUTIONThe generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up.WIDER IMPLICATIONS OF THE FINDINGSSerum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART.STUDY FUNDING/COMPETING INTERESTSNIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare.[...]



Time-varying cycle average and daily variation in ambient air pollution and fecundability

Fri, 10 Nov 2017 00:00:00 GMT

Abstract
STUDY QUESTION
Does ambient air pollution affect fecundability?
SUMMARY ANSWER
While cycle-average air pollution exposure was not associated with fecundability, we observed some associations for acute exposure around ovulation and implantation with fecundability.
WHAT IS KNOWN ALREADY
Ambient air pollution exposure has been associated with adverse pregnancy outcomes and decrements in semen quality.
STUDY DESIGN, SIZE, DURATION
The LIFE study (2005–2009), a prospective time-to-pregnancy study, enrolled 501 couples who were followed for up to one year of attempting pregnancy.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Average air pollutant exposure was assessed for the menstrual cycle before and during the proliferative phase of each observed cycle (n = 500 couples; n = 2360 cycles) and daily acute exposure was assessed for sensitive windows of each observed cycle (n = 440 couples; n = 1897 cycles). Discrete-time survival analysis modeled the association between fecundability and an interquartile range increase in each pollutant, adjusting for co-pollutants, site, age, race/ethnicity, parity, body mass index, smoking, income and education.
MAIN RESULTS AND THE ROLE OF CHANCE
Cycle-average air pollutant exposure was not associated with fecundability. In acute models, fecundability was diminished with exposure to ozone the day before ovulation and nitrogen oxides 8 days post ovulation (fecundability odds ratio [FOR] 0.83, 95% confidence interval [CI]: 0.72, 0.96 and FOR 0.84, 95% CI: 0.71, 0.99, respectively). However, particulate matter ≤10 microns 6 days post ovulation was associated with greater fecundability (FOR 1.25, 95% CI: 1.01, 1.54).
LIMITATIONS, REASONS FOR CAUTION
Although our study was unlikely to be biased due to confounding, misclassification of air pollution exposure and the moderate study size may have limited our ability to detect an association between ambient air pollution and fecundability.
WIDER IMPLICATIONS OF THE FINDINGS
While no associations were observed for cycle-average ambient air pollution exposure, consistent with past research in the United States, exposure during critical windows of hormonal variability was associated with prospectively measured couple fecundability, warranting further investigation.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Longitudinal Investigation of Fertility and the Environment study contract nos. #N01-HD-3-3355, NO1-HD-#-3356, N01-HD-3-3358 and the Air Quality and Reproductive Health Study Contract No. HHSN275200800002I, Task Order No. HHSN27500008). We declare no conflict of interest.



The number of oocytes retrieved during IVF: a balance between efficacy and safety

Fri, 10 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONWhat is the relationship between the number of oocytes collected in fresh IVF treatments and the likelihood of cumulative delivery rate (fresh and frozen) per oocyte aspiration, severe ovarian hyperstimulation syndrome (OHSS) and thromboembolic events?SUMMARY ANSWERCumulative delivery rate per aspiration increases up to 20 oocytes retrieved and then evens out while the incidence of severe OHSS increases more rapidly from around 18 oocytes and thromboembolic events, although rare, occurs in particular if 15 or more oocytes are retrieved.WHAT IS KNOWN ALREADY?Previous studies have shown that the number of oocytes retrieved for IVF is a positive predictor of live birth in fresh cycles. Few studies have investigated cumulative live birth rates and OHSS in relation to the number of aspirated oocytes.STUDY DESIGN, SIZE, DURATIONRetrospective population-based registry study including 39 387 women undergoing 77 956 fresh IVF cycles in the period 2007–2013 and 36 270 consecutive transfers of frozen/thawed embryos in the period 2007–2014.PARTICIPANTS/MATERIALS, SETTING, METHODSData from The Swedish National Quality Registry of Assisted Reproduction (Q-IVF) including all IVF cycles with oocyte retrieval performed in public or private infertility clinics during the study period, was cross-linked to the National Patient Register regarding diagnostic codes (ICD 10) for severe (OHSS) and thromboembolic events. Oocyte donation cycles were excluded.MAIN RESULTS AND THE ROLE OF CHANCELive birth delivery rate in fresh cycles increased up to 11 oocytes retrieved and then evened out, where the live birth rate was 30.3% for a 34-year-old woman. The cumulative delivery rate per aspiration, including fresh transfer and all subsequent transfers of frozen-thawed embryos (FET cycles) per oocyte retrieval, increased up to approximately 20 oocytes where it reached 45.8%. The adjusted odds ratio (AOR) for live birth by the number of oocytes was 1.064 (95% CI: 1.061; 1.067). The incidence of severe OHSS increased significantly by the number of oocytes, particularly if more than 18 oocytes were retrieved. The AOR for OHSS by the number of oocytes was 1.122 (95% CI: 1.08; 1.137). Thromboembolic events were rare, a total of 16 events in 14 patients were observed, and occurred in particular if 15 or more oocytes were retrieved.LIMITATIONS, REASONS FOR CAUTIONAll FET cycles might not be included. Some embryos cryopreserved between 2010 and 2013 might still result in additional births until 2018. Furthermore the gonadotrophin dose was not included in the Q-IVF Registry in the study period, thus adjustment for dose was not possible.WIDER IMPLICATIONS OF THE FINDINGSThe results suggest a shift at approximately 18–20 oocytes where the cumulative delivery rate per aspiration levels off and, at the same time, the incidence of severe OHSS increases more rapidly. Thromboembolic events, although rare, should also be taken into consideration at stimulation regimes for IVF. Evaluating data taking both efficacy and the most serious safety aspects into account, is a new approach and of crucial importance both for patients undergoing IVF and their physicians.STUDY FUNDING/COMPETING INTERESTFinancial support was received through an agreement relating to research and the education of doctors (ALFGBG-70 940) and grant from the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.[...]



The protective role of melatonin in porcine oocyte meiotic failure caused by the exposure to benzo(a)pyrene

Fri, 03 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONDoes melatonin restore the benzo(a)pyrene (BaP)-induced meiotic failure in porcine oocytes?SUMMARY ANSWERMelatonin effectively inhibits the increased reactive oxygen species (ROS) level and apoptotic rate in BaP-exposed porcine oocytes to recover the meiotic failure.WHAT IS KNOWN ALREADYBaP, a widespread environmental carcinogen found in particulate matter, 2.5 µm or less (PM2.5), has been shown to have toxicity at the level of the reproductive systems. BaP exposure disrupts the steroid balance, alters the expression of ovarian estrogen receptor and causes premature ovarian failure through the rapid depletion of the primordial follicle pool. In addition, acute exposure to BaP has transient adverse effects on the follicle growth, ovulation and formation of corpora lutea, which results in transient infertility.STUDY DESIGN, SIZE, DURATIONPorcine oocytes were randomly assigned to control, BaP-exposed and melatonin-supplemented groups. BaP was dissolved in dimethylsulphoxide and diluted to a final concentration of 50, 100 or 250 μM with maturation medium, respectively. Melatonin was dissolved in the absolute ethanol and diluted with maturation medium to a final concentration of 1 nM, 100 nM, 10 μM and 1 mM, respectively. The in vitro cultured oocytes from each group after treatment were applied to the subsequent analysis.PARTICIPANTS/MATERIALS, SETTING, METHODSAcquisition of oocyte meiotic competence was assessed using immunostaining, fluorescent intensity quantification and/or immunoblotting to analyse the cytoskeleton assembly, mitochondrial integrity, cortical granule dynamics, ovastacin distribution, ROS level and apoptotic rate. Fertilization ability of oocytes was examined by sperm binding assay and IVF.MAIN RESULTS AND THE ROLE OF CHANCEBaP exposure resulted in the oocyte meiotic failure (P = 0.001) via impairing the meiotic apparatus, showing a prominently defective spindle assembly (P = 0.003), actin dynamics (P < 0.001) and mitochondrion integrity (P < 0.001). In addition, BaP exposure caused the abnormal distribution of cortical granules (P < 0.001) and ovastacin (P = 0.003), which were consistent with the observation that fewer sperm bound to the zona pellucida surrounding the unfertilized BaP-exposed eggs (P < 0.001), contributing to the fertilization failure (P < 0.001). Conversely, melatonin supplementation recovered, at least partially, all the meiotic defects caused by BaP exposure through inhibiting the rise in ROS level (P = 0.015) and apoptotic rate (P = 0.001).LIMITATIONS, REASONS FOR CAUTIONWe investigated the negative impact of BaP on the oocyte meiotic maturation in vitro, but not in vivo.WIDER IMPLICATIONS OF THE FINDINGSOur findings not only deeply clarify the potential mechanisms of BaP-induced oocyte meiotic failure, but also extend the understanding about how environmental pollutants influence the reproductive systems in humans.STUDY FUNDING/COMPETING INTERESTSThis study was supported by the National Natural Science Foundation of China (31571545) and the Natural Science Foundation of Jiangsu Province (BK20150677). The authors have no conflict of interest to disclose.[...]



Cancer risk in children born after donor ART

Thu, 02 Nov 2017 00:00:00 GMT

AbstractSTUDY QUESTIONDo children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population?SUMMARY ANSWERThis study showed no overall increased risk of childhood cancer in individuals born after donor ART.WHAT IS KNOWN ALREADYMost large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date.STUDY DESIGN, SIZE, DURATIONThis retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992–2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years).PARTICIPANTS/MATERIALS, SETTING, METHODSRecords of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992–2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles.MAIN RESULTS AND THE ROLE OF CHANCEIn our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43–1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25–37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight.LIMITATIONS REASONS FOR CAUTIONAlthough this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available.WIDER IMPLICATIONS OF THE FINDINGSThis is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed.STUDY FUNDING/COMPETING INTEREST(S)This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Govern[...]






Vitamin D and assisted reproductive treatment outcome: a systematic review and meta-analysis

Tue, 31 Oct 2017 00:00:00 GMT

Abstract
STUDY QUESTION
Is serum vitamin D associated with live birth rates in women undergoing ART?
SUMMARY ANSWER
Women undergoing ART who are replete in vitamin D have a higher live birth rate than women who are vitamin D deficient or insufficient.
WHAT IS KNOWN ALREADY
Vitamin D deficiency has been associated with an increased risk of abnormal pregnancy implantation as well as obstetric complications such as pre-eclampsia and fetal growth restriction. However, the effect of vitamin D on conception and early pregnancy outcomes in couples undergoing ART is poorly understood.
STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis of 11 published cohort studies (including 2700 women) investigating the association between vitamin D and ART outcomes.
PARTICIPANTS/MATERIALS, SETTINGS, METHODS
Literature searches were conducted to retrieve studies which reported on the association between vitamin D and ART outcomes. Databases searched included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Eleven studies matched the inclusion criteria.
MAIN RESULTS AND THE ROLE OF CHANCE
Live birth was reported in seven of the included studies (including 2026 patients). Live birth was found to be more likely in women replete in vitamin D when compared to women with deficient or insufficient vitamin D status (OR 1.33 [1.08–1.65]). Five studies (including 1700 patients) found that women replete in vitamin D were more likely to achieve a positive pregnancy test than women deficient or insufficient in vitamin D (OR 1.34 ([1.04–1.73]). All 11 of the included studies (including 2700 patients) reported clinical pregnancy as an outcome. Clinical pregnancy was found to be more likely in women replete in vitamin D (OR 1.46 [1.05–2.02]). Six studies (including 1635 patients) reported miscarriage by vitamin D concentrations. There was no association found between miscarriage and vitamin D concentrations (OR 1.12 [0.81–1.54]. The included studies scored well on the Newcastle-Ottawa quality assessment scale.
LIMITATIONS REASONS FOR CAUTION
Although strict inclusion criteria were used in the conduct of the systematic review, the included studies are heterogeneous in population characteristics and fertility treatment protocols.
WIDER IMPLICATIONS OF THE FINDINGS
The findings of this systematic review show that there is an association between vitamin D status and reproductive treatment outcomes achieved in women undergoing ART. Our results show that vitamin D deficiency and insufficiency could be important conditions to treat in women considering ARTs. A randomized controlled trial to investigate the benefits of vitamin D deficiency treatment should be considered to test this hypothesis.
STUDY FUNDING/COMPETING INTERESTS
No external funding was either sought or obtained for this study. The authors have no competing interests to declare.
REGISTRATION NUMBER
N/A.