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Study questionDoes parental fertility, measured by time to pregnancy (TTP), or use of medically assisted reproduction (MAR) affect pubertal development in the offspring?Summary answerNeither TTP nor type of MAR treatment had clinically relevant implications for mean age at achieving individual pubertal milestones or overall timing of puberty in boys and girls.What is known alreadyParental TTP and MAR have been associated with impaired semen quality in adult sons. Timing of puberty reflects earlier signals of reproductive health, but it remains unclear whether parental fertility or MAR affects pubertal development, especially in the growing generation of children conceived by IVF or ICSI.Study design, size, durationIn this study, 15 819 children born by mothers in the Danish National Birth Cohort from 2000 to 2003 participated in a nationwide puberty cohort (participation rate = 70%). Parental TTP and use of MAR were reported by mothers in early pregnancy and children's pubertal development data was self-recorded in web-based questionnaires from 11 years of age and 6 monthly throughout puberty (2012-2018).Participants/materials, setting, methodsPubertal development in children (of planned pregnancies, n = 13 285) born by untreated subfecund (TTP: 6-12 months) (n =2038), untreated severely subfeund (TTP: >12 months) (n = 1242), treated subfecund (n = 230) and treated severely subfecund (n = 1234) parents were compared to children born to more fertile parents (TTP: ≤5 months). We estimated mean monthly differences in mean age at achieving individual pubertal milestones (i.e. age at menarche, voice break, first ejaculation and Tanner stages 2, 3, 4 and 5 for breast or genital development and pubic hair growth) and a combined indicator of timing of puberty. Further, we compared mean age at achieving the individual pubertal milestones in children born by use of IVF or ICSI (n = 480) with children born by controlled ovarian stimulation or ovulation induction with or wit

Study questionDoes parental fertility, measured by time to pregnancy (TTP), or use of medically assisted reproduction (MAR) affect pubertal development in the offspring?Summary answerNeither TTP nor type of MAR treatment had clinically relevant implications for mean age at achieving individual pubertal milestones or overall timing of puberty in boys and girls.What is known alreadyParental TTP and MAR have been associated with impaired semen quality in adult sons. Timing of puberty reflects earlier signals of reproductive health, but it remains unclear whether parental fertility or MAR affects pubertal development, especially in the growing generation of children conceived by IVF or ICSI.Study design, size, durationIn this study, 15 819 children born by mothers in the Danish National Birth Cohort from 2000 to 2003 participated in a nationwide puberty cohort (participation rate = 70%). Parental TTP and use of MAR were reported by mothers in early pregnancy and children's pubertal development data was self-recorded in web-based questionnaires from 11 years of age and 6 monthly throughout puberty (2012-2018).Participants/materials, setting, methodsPubertal development in children (of planned pregnancies, n = 13 285) born by untreated subfecund (TTP: 6-12 months) (n =2038), untreated severely subfeund (TTP: >12 months) (n = 1242), treated subfecund (n = 230) and treated severely subfecund (n = 1234) parents were compared to children born to more fertile parents (TTP: ≤5 months). We estimated mean monthly differences in mean age at achieving individual pubertal milestones (i.e. age at menarche, voice break, first ejaculation and Tanner stages 2, 3, 4 and 5 for breast or genital development and pubic hair growth) and a combined indicator of timing of puberty. Further, we compared mean age at achieving the individual pubertal milestones in children born by use of IVF or ICSI (n = 480) with children born by controlled ovarian stimulation or ovulation induction with or wit

PurposeThis study investigated the relationship between the vitamin D [25(OH)D] level in individual follicles and oocyte developmental competence.MethodsA prospective cohort study in a private infertility center. Infertile women (N = 198) scheduled for intracytoplasmic sperm injection (ICSI) and a single embryo transfer (SET) provided serum samples and 322 follicular fluid (FF) specimens, each from a single follicle on the day of oocyte retrieval.ResultsFFs corresponding to successfully fertilized oocytes (following ICSI) contained significantly lower 25(OH)D level compared with those that were not fertilized (28.4 vs. 34.0 ng/ml, P = 0.001). Top quality embryos on the third day after fertilization, when compared to other available embryos, developed from oocytes collected from follicles containing significantly lower 25(OH)D levels (24.56 vs. 29.59 ng/ml, P = 0.007). Positive hCG, clinical pregnancy, and live birth rates were achieved from embryos derived from oocytes that grew in FF with significantly lower 25(OH)D levels than in follicles not associated with subsequent pregnancy. The concentration of 25(OH)D in FF in women with negative hCG was 32.23 ± 20.21 ng/ml, positive hCG 23.62 ± 6.09 ng/ml, clinical pregnancy 23.13 ± 6.09 ng/ml, and live birth 23.45 ± 6.11 ng/ml (P < 0.001). Women with serum 25(OH)D < 20 ng/ml had not only a higher fertilization rate (71 vs. 61.6%, P = 0.026) and a higher clinical pregnancy rate (48.2 vs. 25%, P = 0.001), but also higher miscarriage rate (14.5 vs. 3.8%, P = 0.013) compared with those with levels ≥ 20 ng/ml.ConclusionThis study reveals that the level of 25(OH)D in FF correlates negatively with the oocytes' ability to undergo fertilization and subsequent preimplantation embryo development. Oocytes matured in FF with low 25(OH)D concentration are more likely to produce top quality embryos and are associated with higher pregnancy and delivery rates. On the other hand, low serum vit

PurposeThis study investigated the relationship between the vitamin D [25(OH)D] level in individual follicles and oocyte developmental competence.MethodsA prospective cohort study in a private infertility center. Infertile women (N = 198) scheduled for intracytoplasmic sperm injection (ICSI) and a single embryo transfer (SET) provided serum samples and 322 follicular fluid (FF) specimens, each from a single follicle on the day of oocyte retrieval.ResultsFFs corresponding to successfully fertilized oocytes (following ICSI) contained significantly lower 25(OH)D level compared with those that were not fertilized (28.4 vs. 34.0 ng/ml, P = 0.001). Top quality embryos on the third day after fertilization, when compared to other available embryos, developed from oocytes collected from follicles containing significantly lower 25(OH)D levels (24.56 vs. 29.59 ng/ml, P = 0.007). Positive hCG, clinical pregnancy, and live birth rates were achieved from embryos derived from oocytes that grew in FF with significantly lower 25(OH)D levels than in follicles not associated with subsequent pregnancy. The concentration of 25(OH)D in FF in women with negative hCG was 32.23 ± 20.21 ng/ml, positive hCG 23.62 ± 6.09 ng/ml, clinical pregnancy 23.13 ± 6.09 ng/ml, and live birth 23.45 ± 6.11 ng/ml (P < 0.001). Women with serum 25(OH)D < 20 ng/ml had not only a higher fertilization rate (71 vs. 61.6%, P = 0.026) and a higher clinical pregnancy rate (48.2 vs. 25%, P = 0.001), but also higher miscarriage rate (14.5 vs. 3.8%, P = 0.013) compared with those with levels ≥ 20 ng/ml.ConclusionThis study reveals that the level of 25(OH)D in FF correlates negatively with the oocytes' ability to undergo fertilization and subsequent preimplantation embryo development. Oocytes matured in FF with low 25(OH)D concentration are more likely to produce top quality embryos and are associated with higher pregnancy and delivery rates. On the other hand, low serum vit

PURPOSE: This study investigated the relationship between the vitamin D [25(OH)D] level in individual follicles and oocyte developmental competence. METHODS: A prospective cohort study in a private infertility center. Infertile women (N = 198) scheduled for intracytoplasmic sperm injection (ICSI) and a single embryo transfer (SET) provided serum samples and 322 follicular fluid (FF) specimens, each from a single follicle on the day of oocyte retrieval. RESULTS: FFs corresponding to successfully fertilized oocytes (following ICSI) contained significantly lower 25(OH)D level compared with those that were not fertilized (28.4 vs. 34.0 ng/ml, P = 0.001). Top quality embryos on the third day after fertilization, when compared to other available embryos, developed from oocytes collected from follicles containing significantly lower 25(OH)D levels (24.56 vs. 29.59 ng/ml, P = 0.007). Positive hCG, clinical pregnancy, and live birth rates were achieved from embryos derived from oocytes that grew in FF with significantly lower 25(OH)D levels than in follicles not associated with subsequent pregnancy. The concentration of 25(OH)D in FF in women with negative hCG was 32.23 ± 20.21 ng/ml, positive hCG 23.62 ± 6.09 ng/ml, clinical pregnancy 23.13 ± 6.09 ng/ml, and live birth 23.45 ± 6.11 ng/ml (P < 0.001). Women with serum 25(OH)D < 20 ng/ml had not only a higher fertilization rate (71 vs. 61.6%, P = 0.026) and a higher clinical pregnancy rate (48.2 vs. 25%, P = 0.001), but also higher miscarriage rate (14.5 vs. 3.8%, P = 0.013) compared with those with levels ≥ 20 ng/ml. CONCLUSION: This study reveals that the level of 25(OH)D in FF correlates negatively with the oocytes ability to undergo fertilization and subsequent preimplantation embryo development. Oocytes matured in FF with low 25(OH)D concentration are more likely to produce top quality embryos and are associated with higher pregnancy and delivery rates. On the other hand, low

Study questionCan the histone deacetylase inhibitor Scriptaid improve the efficiency of the development of round spermatid injection (ROSI)-fertilized embryos in a mouse model?Summary answerTreatment of ROSI mouse zygotes with Scriptaid increased the expression levels of several development-related genes at the blastocyst stage, resulting in more efficient in vitro development of the blastocyst and an increased birth rate of ROSI-derived embryos.What is known alreadyThe full-term development of embryos derived through ROSI is significantly lower than that following ICSI in humans and other species.Study design, size, durationOocytes, spermatozoa and round spermatids were collected from BDF1 (C57BL/6 × DBA/2) mice. For in vitro development experiments, mouse ROSI-derived zygotes were treated with Scriptaid at different concentrations (0, 125, 250, 500 and 1000 nM) and for different exposure times (0, 6, 10, 16 or 24 h). Next, blastocysts of the optimal Scriptaid-treated group and the non-treated ROSI group were separately transferred into surrogate ICR mice to compare in vivo development with the ICSI group (control). Each experiment was repeated at least three times.Participants/materials, setting, methodsMetaphase II (MII) oocytes, spermatozoa and round spermatids were obtained from sexually mature BDF1 female or male mice. The developmental potential of embryos among the three groups (the ICSI, ROSI and optimal Scriptaid-treated ROSI groups) was assessed based on the rates of obtaining zygotes, two-cell stage embryos, four-cell stage embryos, blastocysts and full-term offspring. In addition, the expression levels of development-related genes (Oct4, Nanog, Klf4 and Sox2) were analysed using real-time PCR, and the methylation states of imprinted genes (H19 and Snrpn) in these three groups were detected using methylation-specific PCR (MS-PCR) sequencing following bisulfite treatment.Main results and the role of chanceThe in vitro experiments revealed that treating RO

OBJECTIVE: To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Forty single-arm open-label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen. INTERVENTION(S): Semen washing followed by IUI, IVF, or IVF/ICSI. PRIMARY OUTCOME: HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy. RESULT(S): No HIV transmission occurred in 11,585 cycles of assisted reproduction with the use of washed semen among 3,994 women. Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women after 2,863 cycles of assisted reproduction with the use of washed semen. Studies that measured HIV transmission to infants reported no cases of vertical transmission. Overall, 56.3% of couples (2,357/4,184) achieved a clinical pregnancy with the use of washed semen. CONCLUSION(S): Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help to further reduce the spread of HIV.

BackgroundThe number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed.MethodsRelevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports.ResultsART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accelerated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures.ConclusionsART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evidence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves. Because g

Objective: To explore patients undergoing complex assisted reproductive technologies’ (ART) opinions on both gamete and embryo donation, as well as the reasons to do it or not. Design: Cross-sectional study of descriptive bioethics, with ethnographic qualitative methodology using a semi-structured interview, applying speech analysis to the resulting written transcript. Setting: Private medical institution, in Lima, Peru. Par ticipants: Twenty women and 12 men who had had at least one complex ART. Interventions: Semi-structured interview, applying speech analysis to the resulting written transcript. Main outcome measures: Opinion on both gamete and embryo donation. Results:Regarding embryo donation, 11 men would donate their embryos for infer tility treatment, 6 for research purposes, and only one rejected both possibilities. On the other hand, all 20 women would donate embryos for infer tility treatment and only 8 for research purposes. Par ticipants who accepted gamete donations did not necessarily think they would donate their own gametes. Conclusions: Results suggest gamete donation is more commented and generally accepted; embryo donation, either to donate or to accept donation, is a more conflicting and less discussed subject. Cryopreservation is a complex subject, commented but also conflicting, whose acceptance or not as well as the probable cryopreserved embryos destiny depend on par ticipants beliefs on life origin, personal ethics, etc. Hypothesis resulting from this study to be verified in future quantitative researches is that embryo donation could take place mainly for infer tility treatment and exceptionally for research, Objetivo: Explorar opiniones de pacientes que han acudido a técnicas de reproducción asistida (TRA) complejas, respecto a la donación de gametos y embriones, así como las razones para hacerlo o no. Diseño: Estudio transversal de bioética descriptiva, con metodología cualitativa etnográfica, mediante entrevista semiestructurada, aplicando análisis del discurso al texto resultante. Lugar: Clínica privada, en Lima, Perú. Participantes: Veinte mujeres y 12 hombres, quienes habían acudido por lo menos a una TRA compleja. Intervenciones: Entrevista semiestructurada, aplicando análisis del discurso al texto resultante. Principales medidas de resultados: Opinión sobre donación de gametos y embriones. Resultados: Respecto a la donación de embriones, 11 de los hombres los donarían con fines de terapia de fertilidad, 6 con fines de investigación y solamente uno rechazó ambas posibilidades de donación. Las 20 mujeres entrevistadas, por su parte, los donarían para terapia de fertilidad y 8 de ellas con fines de investigación. Los participantes que han aceptado gametos donados, no necesariamente piensan que donarían los propios en caso de poder hacerlo. Conclusiones: La donación de gametos es más comentada y generalmente aceptada; la donación de embriones es un tema menos discutido y más conflictivo, tanto para donar como para aceptar. La crio preservación es un tema complejo, comentado pero también conflictivo, cuya aceptación o no, así como el destino de los embriones probablemente crio preservados, depende de las concepciones que se tiene respecto al origen de la vida, la ética personal, entre otros. Se puede plantear una hipótesis, a ser verificada en estudios cuantitativos, de que la donación de embriones podría efectuarse, principalmente, para terapia de fertilidad y excepcionalmente con fines de investigación.

ObjectiveTo determine whether center to center discrepancies in the ability to locate sperm in infertile testes with abnormal histology stems in part from inconsistencies in pathologists' readings of testis biopsies.DesignProspective cohort study.SettingAcademic male infertility practice.Patient(s)Consecutive series of azoospermic men referred with testis biopsy slides between 1998 and 2003.Intervention(s)Testis biopsy histologies on azoospermic patients referred for infertility care were re-reviewed by a single pathologist blinded to the original reading. Subsequent infertility care was guided by the findings from the second histologic reading.Main outcome measure(s)Agreement between the outside and in-house review of testis biopsy readings was assessed with the kappa statistic. Pregnancy outcomes that resulted from clinical decisions informed by the second histologic readings were also assessed.Result(s)Among 113 histologic specimens, re-review was complicated by fixation artifacts in 18 cases (16%) and insufficient biopsy sample size in 13 cases (12%). The kappa score for interobserver agreement in readings was 0.43 (95% CI 0.32-0.054). Mixed histology patterns in particular were underappreciated by outside pathologists (13% of cases on original reading, 36% of cases on review). In 27% of all cases, the differences in biopsy readings had a significant impact on clinical management.Conclusion(s)A correlation between independent testis histology readings in azoospermic men demonstrates frequent inconsistencies. These differences contribute to inaccurate phenotyping of male infertility and can significantly impact the direction of infertility care. These findings highlight the need for a standardized approach to testis histologic review.

ObjectiveTo determine whether center to center discrepancies in the ability to locate sperm in infertile testes with abnormal histology stems in part from inconsistencies in pathologists' readings of testis biopsies.DesignProspective cohort study.SettingAcademic male infertility practice.Patient(s)Consecutive series of azoospermic men referred with testis biopsy slides between 1998 and 2003.Intervention(s)Testis biopsy histologies on azoospermic patients referred for infertility care were re-reviewed by a single pathologist blinded to the original reading. Subsequent infertility care was guided by the findings from the second histologic reading.Main outcome measure(s)Agreement between the outside and in-house review of testis biopsy readings was assessed with the kappa statistic. Pregnancy outcomes that resulted from clinical decisions informed by the second histologic readings were also assessed.Result(s)Among 113 histologic specimens, re-review was complicated by fixation artifacts in 18 cases (16%) and insufficient biopsy sample size in 13 cases (12%). The kappa score for interobserver agreement in readings was 0.43 (95% CI 0.32-0.054). Mixed histology patterns in particular were underappreciated by outside pathologists (13% of cases on original reading, 36% of cases on review). In 27% of all cases, the differences in biopsy readings had a significant impact on clinical management.Conclusion(s)A correlation between independent testis histology readings in azoospermic men demonstrates frequent inconsistencies. These differences contribute to inaccurate phenotyping of male infertility and can significantly impact the direction of infertility care. These findings highlight the need for a standardized approach to testis histologic review.