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Tarin J.J.,University of Valencia | Garcia-Perez M.A.,University of Valencia | Garcia-Perez M.A.,Research Unit INCLIVA | Cano A.,University of Valencia
Reproductive Biology and Endocrinology | Year: 2016

Background: Literature shows the effects of type of cancer and/or anticancer treatment on live birth percentages and/or pregnancy and neonatal complications in female cancer survivors. However, studies analyzing the obstetric and offspring risks of the morbid conditions associated with previous anti-cancer treatments are missing. The present review aims to uncover these risks. Methods: A literature search based on publications up to March 2016 identified by PubMed and references cited in relevant articles. Results: The morbid conditions associated with prior anticancer treatments including chemotherapy, radiotherapy, surgery, and/or hematopoietic stem-cell transplant may induce not only obstetric and neonatal complications but also long-term effects on offspring. Whereas some risks are predominantly evidenced in untreated women others are observed in both treated and untreated women. These risks may be superimposed on those induced by the current women's trend in Western societies to postpone maternity. Conclusions: Medical professionals should be aware and inform female cancer survivors wishing to have a child not only of the short- and long-term risks to themselves and their prospective offspring of previous anticancer treatments, fertility-preservation technologies, and pregnancy itself, but also of those risks linked to the morbid conditions induced by prior anticancer treatments. Once female cancer survivors wishing to have a child have been properly informed about the risks of reproduction, they will be best placed to make decisions of whether or not to have a biological or donor-conceived child. In addition, when medical professionals be aware of these risks, they will be also best placed to provide appropriate treatments before/during pregnancy in order to prevent or alleviate the impact of these morbid conditions on maternal and offspring health. © 2016 The Author(s).

Tari n J.J.,University of Valencia | Go mez-Piquer V.,University of Valencia | Garci a-Palomares S.,University of Valencia | Garci a-Pe rez M.A.,University of Valencia | And 2 more authors.
Reproductive Biology and Endocrinology | Year: 2014

Background: Most human demographic data, particularly those on natural fertility populations, find no relationship or even a positive association between fertility and longevity. The present study aims to ascertain whether there is a trade-off between fertility and longevity in the mouse model. Methods: The study was focused on the first litter produced by 10- to 14-wk-old hybrid (C57BL/6JIco female X CBA/JIco male) mice. A single female/male per litter was individually housed with a male/female at the age of 25 and 52 wk, respectively, until the end of reproductive life in females or natural death in males under controlled housing conditions. Post-reproductive females and virgin mice were reared until natural death. Cox regression models with forward stepwise variable selection were fitted to examine the effect of several fertility variables on expectation of survival times. Results: Virgin females displayed higher life expectancy than virgin males. The relative risk of dying for a virgin male at a particular age was 2.116 [99% confidence interval: 1.317, 3.398] times that of a virgin female. No significant differences on expectation of survival times between virgin and mated females, and between virgin and mated males were found. Furthermore, total number of pups at weaning and total number of litters produced by a dam/stud, time interval between mating and last litter, time interval between litters, and age at last litter were not significant predictors of expectation of survival times in both mated females and mated males. Conclusions: Like in most human studies, the present study evidences no relationship between total number of offspring/litters produced by a dam/stud and expectation of survival times. Moreover, the present data are in agreement with the general phenomenon of a bias in life expectancy in favor of females. © 2014 Tari´n et al.

Tarin J.J.,University of Valencia | Garcia-Perez M.A.,Research Unit INCLIVA | Garcia-Perez M.A.,University of Valencia | Cano A.,University of Valencia | Cano A.,University Hospital Dr Peset
Molecular Reproduction and Development | Year: 2014

SUMMARY: The present bioessay aims to analyze the impact of parental age, cause of infertility, embryo chromosomal anomalies, assisted reproduction technology (ART) treatments, and environmental and occupational exposures to xenobiotics on ART results, particularly on live-birth percentages per transfer. Special attention is paid to analyzing the effects of these factors on the mitochondrial, genetic, and epigenetic traits of gametes and embryos to ascertain the molecular/cellular mechanisms responsible for the relatively low percentages of live births reported year after year in ART cycles. The bias of age distribution of women attending fertility clinics toward the late thirties and beyond and the high incidence of mosaicism found in pre-implantation embryos emerge as the two biggest players in this scenario. Parental reproductive aging and some causes of infertility are associated with mitochondrial, genetic, and epigenetic alterations to gametes. ART treatments such as ovarian stimulation, gamete/embryo cryopreservation, oocyte in vitro maturation, intracytoplasmic sperm injection, in vitro culture system, and embryo biopsy may also induce epigenetic changes in gametes and/or pre-implantation embryos. Finally, exposure to numerous environmental chemicals is linked to sperm genetic and epigenetic defects. Whereas the selective transfer of euploid blastocysts may improve implantation and pregnancy percentages, especially in reproductively older women, it does not guarantee the total absence of mitochondrial and/or epigenetic defects in embryos. The presence of induced and/or inherited DNA epigenetic disturbances in ART offspring is unlikely to be prevented, even by replacing the whole cytoplasm of oocytes using nuclear-genome-transfer technology. Mol. Reprod. Dev. 81: 568-583, 2014. © 2014 Wiley Periodicals, Inc.

Tarin J.J.,University of Valencia | Garcia-Perez M.A.,University of Valencia | Garcia-Perez M.A.,Research Unit INCLIVA | Cano A.,University of Valencia
Reproductive Biology and Endocrinology | Year: 2015

At a time when increasing numbers of lesbians and gays consider parenthood using reproductive assistance in infertility centers, the present review aims to summarize the results obtained so far by lesbians after intrauterine insemination (IUI) and in-vitro fertilization (IVF) using donor spermatozoa (D-IUI and D-IVF, respectively) and gays entering into gestational-surrogacy programs. Data show that gays display normal semen parameters and lesbians exhibit no specific causes of female infertility except perhaps for polycystic ovary syndrome (PCOS) and some PCOS-related factors. Pair-bonded lesbians entering into D-IUI programs, tend to have higher pregnancy and delivery percentages following spontaneous or induced ovulation than single or pair-bound heterosexual women. The only single study reporting success percentages of lesbians after D-IVF provides, however, puzzling results. In particular, pair-bonded lesbians have lower pregnancy and live-birth percentages than pair-bonded heterosexual women in fresh D-IVF cycles but percentages are similar in frozen/thawed D-IVF cycles. Like in lesbians after D-IUI, surrogate women recruited by pair-bonded gays/single men tend to have higher pregnancy percentages and lower miscarriage percentages than surrogate women recruited by heterosexual couples. Notably, all the reports reviewed in the present study are methodologically flawed because of sampling bias, small sample sizes and inadequate use of statistical methods to control for the effects of influential covariates including age, smoking habits, previous gynecological problems, hormonal stimulation type and protocol, and number of prior treatment types and pregnancies/deliveries. Clinicians, reproductive biologists and editors of fertility/infertility journals should make efforts to prevent these deficiencies in future data reporting. © 2015 Tarín et al.; licensee BioMed Central.

Tarin J.J.,University of Valencia | Garcia-Perez M.A.,University of Valencia | Garcia-Perez M.A.,Research Unit INCLIVA | Hermenegildo C.,University of Valencia | And 2 more authors.
Reproductive Biology and Endocrinology | Year: 2014

Background: In Western gender-neutral countries, the sex ratio at birth is estimated to be approximately 1.06. This ratio is lower than the estimated sex ratio at fertilization which ranges from 1.07 to 1.70 depending on the figures of sex ratio at birth and differential embryo/fetal mortality rates taken into account to perform these estimations. Likewise, little is known about the sex ratio at implantation in natural and assisted-reproduction-treatment (ART) cycles. In this bioessay, we aim to estimate the sex ratio at fertilization and implantation using data from embryos generated by standard in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in preimplantation genetic diagnosis cycles. Thereafter, we compare sex ratios at implantation and birth in cleavage- and blastocyst-stage-transfer cycles to propose molecular mechanisms accounting for differences in post-implantation male and female mortality and thereby variations in sex ratios at birth in ART cycles.Methods: A literature review based on publications up to December 2013 identified by PubMed database searches.Results: Sex ratio at both fertilization and implantation is estimated to be between 1.29 and 1.50 in IVF cycles and 1.07 in ICSI cycles. Compared with the estimated sex ratio at implantation, sex ratio at birth is lower in IVF cycles (1.03 after cleavage-stage transfer and 1.25 after blastocyst-stage transfer) but similar and close to unity in ICSI cycles (0.95 after cleavage-stage transfer and 1.04 after blastocyst-stage transfer).Conclusions: In-vitro-culture-induced precocious X-chromosome inactivation together with ICSI-induced decrease in number of trophectoderm cells in female blastocysts may account for preferential female mortality at early post-implantation stages and thereby variations in sex ratios at birth in ART cycles. © 2014 Tarín et al.; licensee BioMed Central Ltd.

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