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Objective To study the association among fertility treatments, treatment protocol, and offspring neoplasm risk up to the age of 18 years. Design A population-based retrospective cohort. Setting Soroka University Medical Center (SUMC), the single tertiary medical center and in vitro fertilization (IVF) unit in southern Israel. Patient(s) All offspring born at the SUMC between the years 1995 and 2018 after IVF treatment (the exposed group) and offspring conceived spontaneously (the unexposed group). Intervention(s) The study was performed at the SUMC, the single tertiary medical center and IVF unit in southern Israel. The exposed and unexposed were matched with a ratio of 1:4, based on maternal age and calendar month of delivery. Data collection included a summary of the couple’s medical records, delivery data, and offspring neoplasm diagnoses. Main Outcome Measure(s) Offspring neoplasm of any kind and time to diagnosis in each of the groups. Result(s) A total of 1,583 exposed and 5,874 offspring were included in the study. The incidences of offspring benign neoplasm were 14 (0.9%) versus 21 (0.4%), and the incidences of malignancies were 17 (1.1%) versus 29 (0.5%) among offspring of the IVF and spontaneous groups, respectively. The association between mode of conception and offspring neoplasm risk remained significant after adjusting for confounders, including mode of delivery and pregnancy complications such as hypertensive disorder, gestational diabetes mellitus, and preterm delivery compared with spontaneously conceived offspring. Among the IVF group, the increased risk for neoplasm was found among offspring who were transferred as fresh embryos, at an earlier stage of development (cleavage stage), or after three or more aspirated oocytes. Conclusion(s) IVF treatment is associated with offspring neoplasm risk; specifically, the risk was greater among offspring who were returned as fresh embryos, at an earlier embryotic stage (cleavage stage), or after three or more aspirated oocytes.

Are obstetric and perinatal complications associated with morphokinetic parameters of embryo development?This proof-of-concept pilot study included a retrospective analysis of embryo morphokinetic parameters of 85 live births following day 5 single blastocyst transfer. Kinetic variables included time interval (hours) from time of pronuclei fading (tPNf) to: time of 2 cells (tPNf-t2), 9 cells (tPNf-t9), morula (tPNf-tM), start of blastulation (tPNf-tSB), full blastocyst (tPNf-tB) and expanded blastocyst (tPNf-tEB). Multivariable logistic models were used to calculate the risk of perinatal complications after adjustment for confounders.The mean interval of tPNf-tSB was significantly longer for newborns with congenital anomalies compared with healthy newborns (79.49 ± 5.78 versus 71.7 ± 6.3, respectively, P = 0.01) and for embryos of women who had gestational diabetes mellitus compared with normoglycemic women (76.56 ± 7.55 versus 71.5 ± 6.13, respectively, P = 0.015). The mean interval of tPNf-t9 was significantly longer for low-birthweight newborns compared with normal weight (49.25 ± 5.54 versus 45.47 ± 4.77, respectively, P = 0.01). Preterm delivery was associated with several longer intervals of cell divisions compared with delivery at term (tPNf-t5: 28.76 ± 3.13 versus 26.64 ± 2.40, respectively, P = 0.01; tPNf-t6: 30.10 ± 3.05 versus 27.68 ± 2.30, respectively, P 0.001; tPNf-t7: 32.08 ± 4.11 versus 28.70 ± 2.67, respectively, P 0.001; tPNf-t8: 34.75 ± 4.95 versus 30.70 ± 4.10, respectively, P 0.001; tPNf-t9: 50.23 ± 5.87 versus 45.44 ± 4.67, respectively, P 0.001). For each of the outcomes, the association remained significant after adjusting for confounders.This study indicates that there may be a possible association between adverse perinatal outcomes and morphokinetic parameters. Larger studies are needed to establish this association.

The newly developed in-vitro activation (IVA) method provides a novel fertility treatment for patients with premature ovarian insufficiency. The IVA method pretends to promote growth of residual ovarian follicles at early stages of their development. Based on preliminary data, poor ovarian response (POR) patients with decreased ovarian reserve (DOR) who have multiple secondary follicles, IVA is a promising technique to promote growth of secondary follicle as well.

In this study, we investigate if children born following assisted reproduction technologies (ARTs) are at an increased risk for long-term ophthalmic complications. For this purpose, a population-based cohort analysis was conducted which included all deliveries between 1991 and 2014 at a single tertiary medical center. Offspring were classified relative to conception method as ART or spontaneous pregnancies. Offspring hospitalizations up to the age of 18 years involving ophthalmic morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan–Meier survival curve was used to compare cumulative hospitalization rates in exposed (ART) and unexposed offspring (spontaneous), and a Cox proportional hazards model was used to control for potential confounders. A total of 243,682 deliveries were included in the study. In that, 1.8% of the deliveries (4364) were of mothers who underwent fertility treatments and 98.2% (239,318) were conceived spontaneously. Offspring born to mothers who underwent fertility treatments had a significantly higher hospitalization rate involving ophthalmic morbidity, as compared to spontaneously conceived offspring (1.2% vs. 1.0%, p = 0.04). The Kaplan–Meier survival curve pointed to a significantly higher cumulative incidence of ophthalmic morbidity following ART (log rank p = 0.02). Cox proportional hazards model was adjusted for maternal age, preterm delivery, maternal hypertensive disorders, diabetes, and mode of delivery which demonstrated ART as an independent risk factor for long-term pediatric ophthalmic morbidity (adjusted hazard ratio = 1.37, CI 1.04–1.80, p-value = 0.02). We concluded that ART is an independent risk factor for long-term ophthalmic morbidity of the offspring.

Sirtuin-1 (SIRT1), a NAD+-dependent deacetylase, is present in the ovarian granulosa cells (GCs) of various species. This study examined the regulation of SIRT1 expression in human granulosa-lutein cells (hGLCs). Two different, structurally unrelated SIRT1 activators, SRT2104 and resveratrol, dose- and time-dependently enhanced SIRT1 (∼2- and 1.5-fold increase at 50 μmol/L for mRNA and protein levels, respectively), whereas EX-527, an inhibitor of SIRT1 deacetylase activity, significantly suppressed SIRT1 protein induced by these activators. Transfecting cells with SIRT1 siRNA molecules efficiently silenced SIRT1 (∼70 % decrease in 48 h post-transfection). Furthermore, the stimulatory effects of SRT2104 on SIRT1 expression observed in non-transfected or in scrambled siRNA-transfected cells were diminished with SIRT1 silencing. The findings described above imply that SIRT1 autoregulates its own expression. Interestingly, SRT2104 elevated cAMP accumulation (1.4-fold) in the culture media of hGLCs which was further augmented in the presence of hCG (2.2-fold); these effects were evident after 12 h of incubation. This additive effect of hCG and SRT2104 on cAMP accumulation may explain the incremental outcome observed on SIRT1 expression (∼3-fold increase from basal level and ∼1.6-fold stimulation for each compound alone) with these two compounds. SIRT1 knockdown diminished SIRT1 induced by forskolin, providing additional evidence that cAMP promotes SIRT1. These findings imply that by activating adenylyl cyclase (hCG or forskolin) and inhibiting phosphodiesterases (SIRT1 activators), these two signals converge to produce an incremental, positive feedback loop on SIRT1 expression. Such a mechanism highlights the importance of maintaining high SIRT1 levels in human luteinized GCs.

BackgroundOligoteratoasthenozoospermia (OTA) combines deteriorated quantity, morphology and motility of the sperm, resulting in male factor infertility.MethodsWe used whole genome genotyping and exome sequencing to identify the mutation causing OTA in four men in a consanguineous Bedouin family. We expressed the normal and mutated proteins tagged with c-Myc at the carboxy termini by transfection with pCDNA3.1 plasmid constructs to evaluate the effects on protein stability in HEK293 cells and on the kinetics of actin repolymerisation in retinal pigment epithelium cells. Patients’ sperm samples were visualised by transmission electron microscopy to determine axoneme structures and were stained with fluorescent phalloidin to visualise the fibrillar (F)-actin.ResultsA homozygous missense mutation in Ciliogenesis Associated TTC17 Interacting Protein (CATIP): c. T103A, p. Phe35Ile, a gene encoding a protein important in actin organisation and ciliogenesis, was identified as the causative mutation with a LOD score of 3.25. The mutation reduces the protein stability compared with the normal protein. Furthermore, overexpression of the normal protein, but not the mutated protein, inhibits repolymerisation of actin after disruption with cytochalasin D. A high percentage of spermatozoa axonemes from patients have abnormalities, as well as disturbances in the distribution of F-actin.ConclusionThis is the first report of a recessive mutation in CATIP in humans. The identified mutation may contribute to asthenozoospermia by its involvement in actin polymerisation and on the actin cytoskeleton. A mouse knockout homozygote for CATIP was reported to demonstrate male infertility as the sole phenotype.

To compare pregnancy outcomes between pregnancies following day 2, day 3, and days 5/6 fresh embryo transfer (ET).A retrospective cohort study including all pregnancies following fresh IVF/intracytoplasmic sperm injection (ICSI) ET cycles performed between January 2014 and December 2015 at Fertility andA total of 534 pregnancies following fresh IVF/ICSI ET on day 2 (The common approach of blastocyst transfer, as high quality of the embryo, has not proven beneficial in terms of live birth rate. Moreover, cleavage stage embryos were not associated with adverse perinatal outcomes. The current data suggest maternal age has an independent effect on live birth.

IndiaPurpose: To evaluate the in vitro impact of ritalinic acid (RA), a major metabolite of methylphenidate (drug to treat attention-deficit hyperactivity disorder), on sperm motility, vitality and oxidative stress.Materials and Methods: Semen samples (n=13) were collected from healthy donors and a semen analysis was performed according to World Health Organization. Density gradient centrifugation was performed to isolate motile sperm. Samples were incubated with different concentrations (0, 1, 10, 100, and 1,000 ng/mL) of RA. The non-exposed group (0 ng/mL) was defined as the control group. Samples were analyzed for motility at different time points (0, 60, 150, 240, and 300 minutes) and for vitality and oxidation reduction potential (ORP) (at 0, 240, and 300 minutes). Sperm motility was assessed manually and motion kinetic parameters were recorded by computer aided semen analysis. Results: RA at any tested concentration significantly increased sperm motility compared to the control in a time-dependent manner with a maximum increase after 240 minutes. Motion kinetic parameters were not comparable. For sperm vitality, supplementation with RA significantly maintained survival at higher levels, while non-treated sperm gradually died. These higher levels of vitality were maintained with rising RA concentrations of up to 1,000 ng/mL. A non-significant trend of increased ORP was observed in all study groups.Conclusions: RA increases sperm motility and maintains vitality at any concentration tested. Therefore, RA might be utilized to improve sperm quality in asthenozoospermic specimens. However, further investigation is ongoing to evaluate the effect of RA on other sperm parameters.

Background This article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999–2018) using a scientometric approach. Methods A stepwise approach was adopted to retrieve scientometric data (articles per year, authors, affiliations, journals, countries) from Scopus and analyze the publication pattern of SDF with reference to key areas of research in the field of Andrology. Results A total of 2121 articles were retrieved related to SDF. Our data revealed an increasing research trend in SDF (n = 33 to n = 173) over the past 20 years (R2 = 0.894). Most productive country in publications was the USA (n = 450), while Agarwal A. (n = 129) being the most productive author. Most of the articles in SDF were primarily focused on lifestyle (n = 157), asthenozoospermia (n = 135) and varicocele (130). Mechanistic studies on SDF were published twice as much as prognostic/diagnostic studies, with significant emphasis on oxidative stress. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was the most widely used technique to evaluate SDF. Publications on SDF related to assisted reproductive techniques also showed a linear increasing trend (R2 = 0.933). Conclusions Our analysis revealed an increasing trend in SDF publications predominantly investigating lifestyle, asthenozoospermia and varicocele conditions with TUNEL being the most widely used technique. A substantial increase in research is warranted to establish SDF as prognostic/diagnostic parameter to evaluate clinical scenarios and ART outcomes.

OBJECTIVE While the impact of fertility treatments on the perinatal outcome is well established, the long-term effects on offspring are yet to be determined. The current study aimed to investigate the risk of long-term obstructive sleep apnea (OSA) among children born following in vitro fertilization (IVF) and ovulation induction (OI) as compared with spontaneously conceived pregnancies. STUDY DESIGN A retrospective population-based cohort study was performed. Exposure was defined as delivery following pregnancies conceived by IVF or OI. Incidence of OSA related hospitalizations of the offspring, up to the age of 18 years, was evaluated. A Kaplan-Meier survival curve and multivariable Cox regression models were used to assess the association. RESULTS During the study period, 242 187 singleton deliveries met the inclusion criteria; 1.1% were conceived following IVF (n = 2603), and 0.7% following OI (n = 1721). Offspring hospitalization rates, involving OSA (n = 1607), were higher among children conceived following IVF and OI pregnancies as compared with the rate in children conceived spontaneously (1.4% vs 1.2% vs 0.7%, respectively; P

Objective This study was aimed to assess the association between ovarian hyperstimulation syndrome (OHSS) and pregnancy complications among women who conceived following fertility treatment. Study Design A retrospective population-based cohort study, including all singleton deliveries of patients conceived following ovulation induction (OI) or in vitro fertilization (IVF) between 1988 and 2016, was conducted. All births occurred in a single tertiary medical center. A comparison was performed between deliveries of women who had experienced OHSS at early gestation and subsequently had a pregnancy and women without OHSS. Women lacking prenatal care, multiple gestations, and stillbirths were excluded from the analyses. A multivariable logistic regression model was used to control for confounders. Results During the study period, 351,373 deliveries met the inclusion criteria, of which 6,748 were deliveries of infants who were conceived by either IVF or OI. Of this study population, 105 cases (1.6%) composed the exposed group, that is, women who had experienced OHSS with a subsequent live birth. In the multivariate analyses, after controlling for confounders, OHSS was not found as an independent risk factor for preeclampsia, gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), preterm delivery (both Conclusion In our population, OHSS was not found as a risk factor for adverse pregnancy and perinatal outcome. In IVF patients, OHSS is a risk factor for preterm delivery before 34 weeks of gestation. Key Points

To assess the impact of post-thawing embryo culture on frozen embryo transfer (FET) outcomes.A retrospective cohort study including 678 consecutive FET cycles performed between the years 2004 and 2017 was conducted. Patients older than 45 years old were excluded. FET cycles were stratified as follows: (1) two-day (2d) embryos thawed and cultured to three-day (3d) versus 3d embryos thawed and transferred; (2) 2d or 3d embryos thawed and cultured to blastocysts versus blastocysts thawed and transferred. AMaternal age, BMI, smoking, and basal FSH of the 2d and 3d cultured embryo group (We could not demonstrate that the post-thaw culture had a significant impact on the outcome of FET cycles.

STUDY QUESTION Can a machine-learning-based model trained in clinical and biological variables support the prediction of the presence or absence of sperm in testicular biopsy in non-obstructive azoospermia (NOA) patients? SUMMARY ANSWER Our machine-learning model was able to accurately predict (AUC of 0.8) the presence or absence of spermatozoa in patients with NOA. WHAT IS KNOWN ALREADY Patients with NOA can conceive with their own biological gametes using ICSI in combination with successful testicular sperm extraction (TESE). Testicular sperm retrieval is successful in up to 50% of men with NOA. However, to the best of our knowledge, there is no existing model that can accurately predict the success of sperm retrieval in TESE. Moreover, machine-learning has never been used for this purpose. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of 119 patients who underwent TESE in a single IVF unit between 1995 and 2017 was conducted. All patients with NOA who underwent TESE during their fertility treatments were included. The development of gradient-boosted trees (GBTs) aimed to predict the presence or absence of spermatozoa in patients with NOA. The accuracy of these GBTs was then compared to a similar multivariate logistic regression model (MvLRM). PARTICIPANTS/MATERIALS, SETTING, METHODS We employed univariate and multivariate binary logistic regression models to predict the probability of successful TESE using a dataset from a retrospective cohort. In addition, we examined various ensemble machine-learning models (GBT and random forest) and evaluated their predictive performance using the leave-one-out cross-validation procedure. A cutoff value for successful/unsuccessful TESE was calculated with receiver operating characteristic (ROC) curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE ROC analysis resulted in an AUC of 0.807 ± 0.032 (95% CI 0.743-0.871) for the proposed GBTs and 0.75 ± 0.052 (95% CI 0.65-0.85) for the MvLRM for the prediction of presence or absence of spermatozoa in patients with NOA. The GBT approach and the MvLRM yielded a sensitivity of 91% vs. 97%, respectively, but the GBT approach has a specificity of 51% compared with 25% for the MvLRM. A total of 78 (65.3%) men with NOA experienced successful TESE. FSH, LH, testosterone, semen volume, age, BMI, ethnicity and testicular size on clinical evaluation were included in these models. LIMITATIONS, REASONS FOR CAUTION This study is a retrospective cohort study, with all the associated inherent biases of such studies. This model was used only for TESE, since micro-TESE is not performed at our center. WIDER IMPLICATIONS OF THE FINDINGS Machine-learning models may lay the foundation for a decision support system for clinicians together with their NOA patients concerning TESE. The findings of this study should be confirmed with further larger and prospective studies. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Division of Obstetrics and Gynecology, Soroka University Medical Center, there are no potential conflicts of interest for all authors.

Endothelin-2 (EDN2) expression in granulosa cells was previously shown to be highly dependent on the hypoxic mediator, hypoxia inducible factor 1 alpha (HIF1A). Here, we investigated whether sirtuin-1 (SIRT1), by deacetylating HIF1A and class III histones, modulates EDN2 in human granulosa-lutein cells (hGLCs). We found that HIF1A was markedly suppressed in the presence of resveratrol or a specific SIRT1 activator, SRT2104. In turn, hypoxia reduced SIRT1 levels, implying a mutually inhibitory interaction between hypoxia (HIF1A) and SIRT1. Consistent with reduced HIF1A transcriptional activity, SIRT1 activators, resveratrol, SRT2104, and metformin, each acting via different mechanisms, significantly inhibited EDN2. In support, knockdown of SIRT1 with siRNA markedly elevated EDN2, whereas adding SRT2104 to SIRT1-silenced cells abolished the stimulatory effect of siSIRT1 on EDN2 levels further demonstrating that EDN2 is negatively correlated with SIRT1. Next, we investigated whether SIRT1 can also mediate the repression of the EDN2 promoter via histone modification. Chromatin immunoprecipitation (ChIP) analysis revealed that SIRT1 is indeed bound to the EDN2 promoter and that elevated SIRT1 induced a 40% decrease in the acetylation of histone H3, suggesting that SIRT1 inhibits EDN2 promoter activity by inducing a repressive histone configuration. Importantly, SIRT1 activation, using SRT2104 or resveratrol, decreased the viable numbers of hGLC, and silencing SIRT1 enhanced hGLC viability. This effect may be mediated by reducing HIF1A and EDN2 levels, shown to promote cell survival. Taken together, these findings propose novel, physiologically relevant roles for SIRT1 in downregulating EDN2 and survival of hGLCs.

The present study investigated the association between oocyte zona pellucida shear modulus (ZPSM) and implantation rate (IR). Ninety-three oocytes collected from 38 in-vitro fertilization patients who underwent intracytoplasmic sperm injection were included in this case–control study. The ZP was modeled as an isotropic compressible hyperelastic material with parameter $$C_{10}$$ C 10 , which represents the ZPSM. Computational methodology was used to calculate the mechanical parameters that govern ZP deformation. Fifty-one developed embryos were transferred and divided into two groups—implanted and not implanted. Multivariate logistic regression analysis was performed to identify the association between ZPSM and IR while controlling for confounders. Maternal age and number of embryos per transfer were significantly associated with implantation. The IR of embryos characterized by $$C_{10}$$ C 10 values in the range of 0.20–0.40 kPa was 66.75%, while outside this range it was 6.70%. This range was significantly associated with implantation (p p = 0.001). The present study suggests that ZPSM may improve the classic embryo selection process with the aim of increasing IR.

Male fertility preservation has been steadily increasing over the past two decades. Significant improvements have been achieved in the treatment modalities of cancer and other severe chronic medical conditions, leading to an increase in patient survivorship and the resulting demand for future parenthood. Recognition and proper patient counselling before commencing therapies with a potential gonadotoxic effect are of paramount importance. Similarly, nonmedically indicated fertility preservation is on the rise. Social sperm banking, gender dysphoria prior to affirmation procedures and posthumous reproduction preservation are becoming more common. When timing and logistics are appropriate, sperm cryopreservation is considered the gold standard for fertility preservation. Testicular tissue and spermatogonial stem cell autotransplantation is considered experimental and represents a promising alternative for pre-pubertal patients. The current paper aims to review the recent trends in male fertility preservation, the common indications for sperm cryopreservation, techniques for sperm retrieval and experimental frontiers.

Background Despite the endocrine basis of several infertility etiologies, data on long-term endocrine consequences in offspring conceived following fertility treatments remain limited. Aim To determine the risk of long-term endocrine disorders among children born after in-vitro fertilization (IVF) and ovulation induction (OI) as compared with spontaneous pregnancies. Study design, subjects, and outcome measures A population-based cohort study including all singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center was performed. Hospitalization rates up to the age of 18 years involving endocrine disorders were compared between children delivered following pregnancies achieved by IVF, OI, and spontaneous pregnancies. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence. A Cox regression model was used to control for confounders. Results During the study period, 242,187 singleton deliveries met the inclusion criteria; 1.0% were following IVF (n = 2603), 0.7% following OI (n = 1721), and the remaining (n = 237,863) were following spontaneous conceptions. Hospitalizations up to the age of 18 years involving endocrine disorders were comparable in children delivered following IVF (0.4%), OI (0.8%) and spontaneous pregnancies (0.5%; p = 0.09). The Kaplan-Meier survival curve demonstrated comparable cumulative incidence of endocrine morbidity following IVF and OI (log-rank p = 0.30). Using the Cox regression model while controlling for confounders, no significant association was noted between IVF (adjusted HR = 0.95, CI 0.51–1.87), or OI (adjusted HR = 1.32, CI 0.78–2.24) conceived pregnancies, and long-term pediatric endocrine morbidity. Conclusions Singletons conceived via fertility treatment do not appear to be at an increased risk for long-term endocrine disorders.

To investigate risk factors and pregnancy outcome of spontaneous vs in-vitro fertilization (IVF) twins complicated with preeclampsia. A retrospective population-based cohort study comparing maternal and neonatal outcome in IVF vs spontaneously conceived twins was conducted. Deliveries occurred in a tertiary medical center between the years 1988 and 2010. Women who conceived after ovulation induction and those with chronic hypertension were excluded from the study. Multiple logistic regression models were used to control for confounders. The study population included 4428 twin pregnancies, of these 314 (7.1%) had preeclampsia; 64 (20.3%) were IVF twins and 250 (79.7%) were spontaneous twins. Preeclampsia was more common in IVF compare to spontaneous twins (13.8 vs 7.6%, OR = 1.81, CI = 1.50–2.17, P

The aim of this study was to compare the in vitro fertilization (IVF) cycles ended by miscarriage with subsequent IVF cycles in relation to various IVF cycle parameters and pregnancy termination modalities. Comparison of pre-miscarriage to post-miscarriage IVF cycles parameters demonstrated that lower peak E2 levels (1087 ± 593 versus 1237 ± 676 pg/ml, respectively; p < 0.05) were achieved in the post miscarriage cycles despite higher total gonadotropin consumption (2341 ± 1488 versus 2115 ± 1101 IU; p

Background Azoospermia is diagnosed when sperm cells are completely absent in the ejaculate even after centrifugation. It is identified in approximately 1% of all men and in 10%–20% of infertile males. Non-obstructive azoospermia (NOA) is characterised by the absence of sperm due to either a Sertoli cell-only pattern, maturation arrest, hypospermatogenesis or mixed patterns. NOA is a severe form of male infertility, with limited treatment options and low fertility success rates. In the majority of patients, the cause for NOA is not known and mutations in only a few genes were shown to be causative. Aim We investigated the cause of maturation arrest in five azoospermic infertile men of a large consanguineous Bedouin family. Methods and results Using whole genome genotyping and exome sequencing we identified a 4 bp deletion frameshift mutation in TDRD9 as the causative mutation with a Lod Score of 3.42. We demonstrate that the mutation results in a frameshift as well as exon skipping. Immunofluorescent staining with anti-TDRD9 antibody directed towards the N terminus demonstrated the presence of the protein in testicular biopsies of patients with an intracellular distribution comparable to a control biopsy. The mutation does not cause female infertility. Conclusion This is the first report of a recessive deleterious mutation in TDRD9 in humans. The clinical phenotype recapitulates that observed in the Tdrd9 knockout mice where this gene was demonstrated to participate in long interspersed element-1 retrotransposon silencing. If this function is preserved in human, our data underscore the importance of maintaining DNA stability in the human male germ line.

Background Prevalence of pregnancies conceived following fertility treatments is high worldwide. While the impact of fertility treatments on short-term perinatal outcome is well established, long-term consequences are yet to be determined. Objective To study the association between mode of conception and long-term gastrointestinal morbidity among children born following fertility treatments. Study design A population-based cohort analysis including all singleton deliveries occurring between 1991 and 2014 at a single regional tertiary medical center was performed. Fetuses with congenital malformations were excluded. A comparison was performed between children delivered following IVF, OI and spontaneous pregnancies. Hospitalizations up to the age of 18 years involving gastrointestinal morbidity were evaluated. Kaplan-Meier survival curve was used to compare cumulative morbidity incidence. A Cox regression model was used to control for confounders. Results During the study period 242,187 singleton deliveries met the inclusion criteria; 1.1% following IVF (n = 2603), and 0.7% following OI (n = 1721). Hospitalization rates involving gastrointestinal morbidity were significantly higher in children conceived following IVF and OI (5.7%, 7.1% respectively) as compared with children conceived spontaneously (5.4%; p = 0.005). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of gastrointestinal morbidity following IVF and OI (log rank p = 0.001). Using a Cox proportional hazards model, controlling for maternal age, preterm delivery, birthweight, maternal diabetes and hypertensive disorders in pregnancy, IVF (adjusted HR = 1.27, CI 1.08–1.50, p = 0.004), was noted as an independent risk factor for long-term pediatric gastrointestinal morbidity. Conclusion Singletons conceived by IVF appear to be at an increased risk for long-term gastrointestinal morbidity.

Oligoteratoasthenozoospermia (OTA) combines deteriorated quantity, morphology and motility of the sperm, resulting in male factor infertility.We used whole genome genotyping and exome sequencing to identify the mutation causing OTA in four men in a consanguineous Bedouin family. We expressed the normal and mutated proteins tagged with c-Myc at the carboxy termini by transfection with pCDNA3.1 plasmid constructs to evaluate the effects on protein stability in HEK293 cells and on the kinetics of actin repolymerisation in retinal pigment epithelium cells. Patients' sperm samples were visualised by transmission electron microscopy to determine axoneme structures and were stained with fluorescent phalloidin to visualise the fibrillar (F)-actin.A homozygous missense mutation in Ciliogenesis Associated TTC17 Interacting Protein (This is the first report of a recessive mutation in

Numerous studies have attempted to assess the effects of smoking on male reproductive physiology, including sperm parameters, male reproductive anatomy, as well as the male hormonal axes. Yet the results have been equivocal and contradictory. Our objective was to compile the current literature regarding how cigarette smoke exposure can contribute to male infertility. Environmental factors make it difficult to unravel the effects of smoking versus other lifestyle elements. However, with the increased efforts to limit smoke exposure, it is important to parse out potential reversible effects of smoking on the human body. It is well established that toxins in cigarette smoke produce radical oxygen species that cause oxidative damage to nearly every organ system. This increased stress has cascading effects stemming from an impaired hormonal axis, down to causing immotile spermatocytes. Disrupting the normal hormonal axis responsible for reproductive signaling; impairing correct, healthy spermatogenesis; and causing direct damage to mature sperm products are but a few of the etiologies of how smoking can contribute to male infertility.

This study aimed to assess the association between maternal-isolated oligohydramnios (IO) and offspring long-term neurological complications. A population-based retrospective cohort study was conducted, including all births at a single tertiary medical center in Israel between the years 1991 and 2014. Multiple pregnancies and potential pregnancy complications associated with oligohydramnios were excluded. The computerized obstetrical database was linked with the computerized dataset of all pediatric hospitalizations of the same medical center. Evaluation of cumulative neurological-associated hospitalizations rate over time was compared using a Kaplan–Meier survival curve. The Weibull survival parametric model was conducted to assess the neurological-associated hospitalization risk in the presence of IO, while accounting for potential confounders. A total of 190,259 pregnancies were included in the study, of which 4063 (2.13%) pregnancies were complicated with IO. Total neurological-related hospitalizations were significantly more common in the IO group (3.7% in the IO group and 3.0% in the comparison group,p = 0.005). Pervasive developmental disorder, movement disorders, developmental disorders, and degenerative and demyelization disorders were all specific neurological diagnoses significantly more common in the exposed group. The survival curve demonstrated a significantly higher cumulative hospitalization rate in the exposed group (log-rankp= 0.001). Using a multivariate model adjusting for gestational age, maternal age, and labor induction, an independent association between IO and long-term neurological morbidity of the offspring was observed (adjusted hazard ratio 1.203; 95% CI 1.02–1.42). In summary, a significant association was found between pregnancies complicated by IO and long-term neurological morbidity of the offspring.

Endometrial scratching (ES) using a biopsy catheter prior to the IVF cycle in the repeated implantation failure (RIF) population has been suggested, but no convincing evidence of its benefit has been presented until now. A retrospective mono-center study among 300 consecutive IVF-RIF cycles following evaluation of the ovarian reserve, hysterosalpingography or hysteroscopy, pelvic ultrasound, thrombophilia evaluation, karyotyping and assessment of male sperm parametrs. The findings within normal limits. All the patients offered ES, 78 consented and underwent ES prior to their next IVF cycle. A comparison of treatment outcomes between the post-ES cycles (n = 78) and the non-ES cycles (222) demonstrated the following: 34 (43.5%) versus 14 (6.3%) conceptions, respectively (p = 0.001) and 30 (38.4%) versus 2 (0.9%) clinical pregnancies, respectively (p

Objective To study the association between mode of conception and offspring infectious morbidity risk. Design Population-based cohort study. Setting Regional university medical center. Patient(s) All singleton infants born between the years 1991 and 2014 and discharged alive from the hospital. Intervention(s) Follow-up time in the study was calculated from birth to an event, defined as the first offspring hospitalization with any infectious morbidity. All infectious diagnoses were compared between the study groups, and a multivariable survival model was created to study the association between mode of conception and offspring pediatric hospitalization with infectious morbidity, and adjusting for confounding or clinically significant variables. Main Outcome Measure(s) First offspring pediatric hospitalization with infectious morbidity. Result(s) During the study period, 242,187 newborns met the inclusion criteria: 2,603 (1.1%) of which were conceived after undergoing IVF, 1,172 (0.7%) after ovulation induction (OI), and 237,863 (98.3%) were conceived spontaneously. Mothers receiving fertility treatments were older and with higher rates of preterm births and low birthweights. The hospitalizations rates per 1,000 person years of follow-up were 16.34/1,000 person years, 11.61/1,000 person years, and 10.19/1,000 person years, among the IVF, OI, and spontaneously conceived offspring, respectively. The adjusted hazard ratios were 1.26 (95% confidence interval 1.13–1.42) and 1.14 (95% confidence interval 1.00–1.38), for the IVF and OI compared with the spontaneously conceived offspring, respectively. The model adjusted for preterm delivery, birthweight, maternal age, hypertension, diabetes, and cesarean section. Conclusion(s) Higher risk for infectious morbidity was found among offspring conceived after fertility treatments compared with spontaneously conceived offspring.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Granulosa-lutein cells (GLCs) from PCOS women display reduced HIF-1α and EDN2 levels, suggesting their role in PCOS etiology. Here, we investigated the mechanisms involved in aberrant EDN2 expression in PCOS, and its association with HIF-1α. Various HIF-1α-dependent factors were studied in GLCs from PCOS and compared to normally ovulating women. MicroRNA-210 (miR-210), its target genes (SDHD and GPD1L), and HIF-1α-responsive genes (EDN2 and VEGFA) differed in GLCs from PCOS, compared with those of healthy women. Levels of miR-210—designated hypoxiamiR—and EDN2 were reduced in the PCOS GLCs, concomitantly, GPD1L and SDHD levels were elevated. Cultured GLCs retained low EDN2 expression and had low HIF-1α levels, providing evidence for a disrupted hypoxic response in the PCOS GLCs. However, VEGFA expression was elevated in these cells. Next, miR-210 levels were manipulated. miR-210-mimic stimulated EDN2 twice as much as the miR-NC-transfected cells, whereas miR-210-inhibitor diminished EDN2, emphasizing the importance of hypoxiamiR for EDN2 induction. Intriguingly, VEGFA transcripts were reduced by both miR-210-mimic and -inhibitor, demonstrating that EDN2 and VEGFA are distinctly regulated. Disrupted hypoxic response in the GLCs of periovulatory follicles in PCOS women may play a role in ovulation failure, and in the reduced fertility prevalent in this syndrome.

Objective Approximately 37% of men of reproductive age smoke cigarettes, with Europe having the highest tobacco use among all the World Health Organization (WHO) regions. Toxins from tobacco smoking can potentially affect sperm development and function, with a negative effect on semen parameters. Given the high prevalence of smoking and recent changes in the WHO laboratory methods for the examination of human semen, the role of this exposure in face of new WHO methods needs to be clarified. Evidence acquisition We conducted a systematic review, followed by a meta-analysis, to determine whether cigarette smoking affects human semen parameters. PubMed, Saint Joseph's University Discover, and Google Scholar were used to identify relevant studies published after release of the latest WHO methods for laboratory evaluation of human semen. Participants were from fertility/urologic clinics and andrology laboratories. The outcome measures were semen volume, sperm concentration, motility, and morphology, the parameters usually used in clinical settings to assess fertility. Evidence synthesis Twenty studies with 5865 participants were included in the meta-analysis. Exposure to cigarette smoking was associated with reduced sperm count (mean difference [MD]: −9.72×10 6 /ml; 95% confidence interval [CI], −13.32 to −6.12), motility (MD: −3.48%; 95% CI, −5.53 to −1.44), and morphology (MD: −1.37%; 95% CI, −2.63 to −0.11). Subgroup analyses indicated that effect size was higher in infertile men than in the general population and in moderate/heavy smokers than in mild smokers. The overall effect size on semen volume, sperm count, and motility remained similar when 2010 and earlier WHO manuals were used for semen analysis but was lower with regard to sperm morphology. Conclusions Our results suggest that cigarette smoking has an overall negative effect on semen parameters. The latest WHO laboratory methods for the examination of human semen had a minimal impact on the magnitude of effect size, thus confirming the observed negative effect of smoking on conventional semen parameters. Patient summary A new systematic review and meta-analysis comprising 5865 men shows that cigarette smoking is associated with reduced sperm count and motility. Deterioration of semen quality is more pronounced in moderate and heavy smokers.

Infertility, defined as the inability to achieve pregnancy after 12 months of unprotected intercourse (1), affects approximately 15% of the couples at reproductive age (2,3). Globally, infertility rates are increasing (4) and as a consequence the use of fertility treatments for conceiving are growing. Since the birth of Louise Brown in 1978, more than 5 million children have been born by fertility treatments in the last 40 years worldwide (5). The etiology of infertility is multifactorial and may include female factors such as anovulation and mechanical issues as well as male factors, mainly abnormal sperm count or function. Yet, male infertility accounts for 30–55% of infertility among couples (6).

Purpose To evaluate the in vitro impact of ritalinic acid (RA), a major metabolite of methylphenidate (drug to treat attention-deficit hyperactivity disorder), on sperm motility, vitality and oxidative stress. Materials and Methods Semen samples (n=13) were collected from healthy donors and a semen analysis was performed according to World Health Organization. Density gradient centrifugation was performed to isolate motile sperm. Samples were incubated with different concentrations (0, 1, 10, 100, and 1,000 ng/mL) of RA. The non-exposed group (0 ng/mL) was defined as the control group. Samples were analyzed for motility at different time points (0, 60, 150, 240, and 300 minutes) and for vitality and oxidation reduction potential (ORP) (at 0, 240, and 300 minutes). Sperm motility was assessed manually and motion kinetic parameters were recorded by computer aided semen analysis. Results RA at any tested concentration significantly increased sperm motility compared to the control in a time-dependent manner with a maximum increase after 240 minutes. Motion kinetic parameters were not comparable. For sperm vitality, supplementation with RA significantly maintained survival at higher levels, while non-treated sperm gradually died. These higher levels of vitality were maintained with rising RA concentrations of up to 1,000 ng/mL. A non-significant trend of increased ORP was observed in all study groups. Conclusions RA increases sperm motility and maintains vitality at any concentration tested. Therefore, RA might be utilized to improve sperm quality in asthenozoospermic specimens. However, further investigation is ongoing to evaluate the effect of RA on other sperm parameters.

Uterine fibroids are a common morbidity in women and its prevalence is increasing with age. As maternal age rises, fibroids become more prevalent during pregnancy.To assess perinatal outcome and long-term health of children to mothers with uterine fibroids during pregnancy.A population-based cohort analysis assessing long-term hospitalizations of offspring, up to the age of 18 years, due to gastrointestinal, neurological, cardiovascular, endocrine, and respiratory morbidity, following pregnancies diagnosed with and without a fibroid uterus. Multivariable generalized estimating equation (GEE) analysis adjusted for maternal clusters and other possible confounders was performed. Kaplan-Meier survival curves and Cox survival regression models were used to compare cumulative morbidity incidence and control for confounders.All singleton deliveries occurring between 1991 and 2014.Perinatal outcome and long-term pediatric morbidity.A total of 242,445 singleton deliveries were included; 0.5% of which were diagnosed with uterine fibroids (n = 1237). In the GEE multivariable analyses, advanced maternal age, hypertensive disorder and diabetes mellitus, fetal growth restriction, low birthweight (2500 g), and small for gestational age newborns, were all independently associated with uterine fibroids during pregnancy. Hospitalizations up to the age of 18 years in the different health categories were comparable between the groups, using Cox regression models, controlled for clinically significant confounders in the long-term outcomes.Maternal uterine fibroids appear to negatively impact perinatal outcome, mainly fetal growth. However, no independent major impact on future health of the offspring can be detected.

Objective: We aimed to evaluate the association between advanced maternal age and the long-term health of the offspring. Methods: In this population-based cohort study, hospitalizations of offspring up to the age of 18 years were compared according to maternal age. The incidence of long-term hospitalizations of the offspring due to cardiovascular, endocrine, neurological, hematological, respiratory and gastro­intestinal morbidities was evaluated. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence. Cox regression models were performed to control for confounders. Results: During the study period, 202,709 deliveries were included, of which 26,287 (12.9%) were in women aged 35–39 years, and 6,718 (3.3%) in women aged 40–50 years. Children born to older mothers did not have a significantly different cumulative incidence of long-term pediatric morbidities evaluated, as compared with the comparison group, using Kaplan-Meier survival analyses. In the Cox regression analyses, advanced maternal age did not exhibit an independent association with long-term morbidities of the offspring. Conclusion: Despite the association of advanced maternal age with adverse maternal and immediate neonatal outcomes, there does not seem to be an association with the long-term morbidity of the offspring.

Research question To assess the perinatal and obstetric outcomes of twin pregnancies resulting from IVF frozen embryo transfer (FET) in comparison with fresh embryo transfer. Design A retrospective cohort study of 773 twin pregnancies conceived via IVF treatment. Data were collected from the records of two outpatient fertility IVF clinics of cycles conducted between 2006 and 2016. Results A total of 773 pregnancies were evaluated: 614 (79.4%) following FET and 159 (20.6%) following fresh embryo transfer. The FET group had a significantly higher mean birthweight (P = 0.002), and lower rates of small for gestational age (P = 0.003), low (P = 0.003) and very low birthweight (P = 0.006) infants. Also, a significantly lower rate of spontaneous second trimester miscarriage compared with the fresh embryo transfer group was observed (P = 0.001). No significant difference was found between groups regarding gestational age at delivery, term birth (after 37 weeks of gestation), twin discordancy rate, fetal major malformation rate, and hospitalization duration. Conclusion In twin pregnancies, FET might have better perinatal outcomes compared with fresh embryo transfer in regards to birthweight and spontaneous second trimester miscarriages. Further research is needed to evaluate these results.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Traditionally, the success of a researcher is assessed by the number of publications he or she publishes in peer-reviewed, indexed, high impact journals. This essential yardstick, often referred to as the impact of a specific researcher, is assessed through the use of various metrics. While researchers may be acquainted with such matrices, many do not know how to use them to enhance their careers. In addition to these metrics, a number of other factors should be taken into consideration to objectively evaluate a scientist′s profile as a researcher and academician. Moreover, each metric has its own limitations that need to be considered when selecting an appropriate metric for evaluation. This paper provides a broad overview of the wide array of metrics currently in use in academia and research. Popular metrics are discussed and defined, including traditional metrics and article-level metrics, some of which are applied to researchers for a greater understanding of a particular concept, including varicocele that is the thematic area of this Special Issue of Asian Journal of Andrology. We recommend the combined use of quantitative and qualitative evaluation using judiciously selected metrics for a more objective assessment of scholarly output and research impact

This study investigated the effects of varicocele on semen parameters in infertile men based on the new 2010 World Health Organization laboratory manual for the examination of human semen. Semen analysis results (volume, sperm count, motility, and morphology) were the primary outcomes. An electronic search to collect the data was conducted using the Medline/PubMed, SJU discover, and Google Scholar databases. We searched articles published from 2010 to August 2015, i.e., after the publication of the 2010 WHO manual. We included only those studies that reported the actual semen parameters of adult infertile men diagnosed with clinical varicocele and contained a control group of either fertile men or normozoospermic men who were not diagnosed with varicocele. Ten studies were included in the meta-analysis, involving 1232 men. Varicocele was associated with reduced sperm count (mean difference: −44.48 × 10 [6] ml−1 ; 95% CI: −61.45, −27.51 × 10 [6] ml−1 ; P < 0.001), motility (mean difference: −26.67%; 95% CI: −34.27, −19.08; P < 0.001), and morphology (mean difference: −19.68%; 95% CI: −29.28, −10.07; P < 0.001) but not semen volume (mean difference: −0.23 ml; 95% CI: −0.64, 0.17). Subgroup analyses indicated that the magnitude of effect was influenced by control subtype but not WHO laboratory manual edition used for semen assessment. We conclude that varicocele is a significant risk factor that negatively affects semen quality, but the observed pooled effect size on semen parameters does not seem to be affected by the WHO laboratory manual edition. Given most of the studies published after 2010 still utilized the 1999 manual for semen analysis, further research is required to fully understand the clinical implication of the 2010 WHO laboratory manual on the association between varicocele and semen parameters.

Introduction: Polycystic Ovarian Syndrome (PCOS), commonly found in 5% of all women of reproductive age is a heterogeneous endocrine disorder in which woman’s levels of estrogen and progesterone are imbalance leading to the growth of benign masses in the ovaries (ovarian cysts). Rotterdam criteria used to diagnose PCOS include two of three clinical features: 1) oligo- or anovulation, 2) hyperandroginism e.g., hirsutism, acne etc. and 3) sonographic morphologic evidence of polycystic ovaries. Aim: To investigate the relationship between circulating biomarkers and their heterogeneity in PCOS. Material and Methods: A prospective case control study was conducted including 70 females of age ranging from 20 to 35 y out of which 20 served as healthy controls and 50 were patients of PCOS. Lipid levels, renal profile and antioxidative status of Malondialdehyde (MDA), Catalase (CAT), Superoxide dismutase (SOD) and Reduced glutathione (GSH) was analysed quantitatively. Serum electrolytes (Na+, K+, Mg2+, PO4 -3), anti-oxidants vitamins C and E and steroidal hormones like Follicle Stimulating Hormone (FSH), Sex Hormone Binding Globulin (SHBG) were measured by the commercially available kits. Results: A total of 70 patients were enrolled to the study. Serum electrolytes level like potassium (K) and Phosphorus (P) were significantly increased while antioxidants were decreased in the study group as compared to the control group. Oxidative stress was also increased with higher levels of MDA. Follicle Stimulating Hormone (FSH) and Sex Hormone Binding Globulin (SHBG) were decreased in the study group. The PCOS patients showed statistically significant correlation among the circulating biomarkers like FSH vs. prolactin (r=0.400**). Conclusion: PCOS is found strongly associated with increased lipid peroxidation, oxidative stress, electrolyte imbalance as well as variation in lipid profile in biological system. As the lipid peroxidation increases it increases MDA (end product of lipid peroxidation), significantly it characterize PCOS by quantifying lipid hydroperoxides and therefore it may serve as a good biomarker of oxidative stress of PCOS.

Excessive sperm DNA fragmentation is linked to male infertility as well as health and behavior issues in the offspring. The three primary mechanisms of sperm DNA damage are impaired spermatogenesis, abortive apoptosis, and oxidative stress. In this chapter, lifestyle factors such as obesity, nutrition, smoking, and alcohol consumption as well as exposure to radiation are all examined as they may increase sperm DNA damage and DNA fragmentation. While the impact of obesity on sperm DNA fragmentation is controversial, a high-fat diet is clearly correlated with loss of sperm DNA integrity, which is contrary to a healthy diet that is high in nuts, vegetables, and fruits. Smoking is only correlated with sperm DNA damage in certain populations, which is explained by the fact that men with certain polymorphisms suffer greater DNA damage from smoking than others. Alcohol and radiation exposures (hospital occupational exposure, X-rays, radiotherapy, and cell phones) are clearly associated with high sperm DNA fragmentation. The mentioned factors may be part of the worldwide observed reduction in semen parameters and sperm function. Identifying these risk factors is important for patient counseling, treatment, and research into alleviating factors.

Background Although concerns have been raised regarding the long-term health risks of offspring conceived following fertility treatments, limited information is available regarding their health status beyond the neonatal period. We aimed to evaluate the risk of long-term eruptive dermatological morbidity among children born following fertility treatments as compared to those conceived spontaneously. Methods A population-based cohort study was conducted, including all singleton deliveries occurring between the years 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations and multiple gestations were excluded. Children delivered following fertility treatment pregnancies and spontaneous pregnancies were compared. Hospitalizations of the offspring up to the age of 18 years involving cutaneous eruptions were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence and a Cox regression model to control for confounders. Results During the study period, 242,187 singleton deliveries met the inclusion criteria, 1.8% of which were following fertility treatments (n = 4324). Eruptive dermatological morbidity of the offspring up to the age of 18 years was significantly more common in the fertility treatment group (1.5%) as compared to spontaneous pregnancies (1.1%; P = 0.023). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of eruptive dermatological morbidity following fertility treatments (log-rank P = 0.007). Using the Cox regression model, while controlling for multiple confounders, fertility treatment was noted as an independent risk factor for long-term pediatric eruptive dermatological morbidity (adjusted HR = 1.43, CI 1.12-1.83, P = 0.004). Conclusion Singletons conceived via fertility treatments appear to be at an increased risk for long-term eruptive dermatological morbidity.