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Objective: Chromosomal aberrations represent an important cause of sterility and infertility; the frequency ranging from 2% to 15%. Secretory azoospermia represents the highest incidence. Chromosomal alterations in males may affect spermatogenesis. These patients are at risk of transmitting such imbalances to their descendants. In this study, we retrospectively analysed a series of males with different categories of chromosomal alterations to estimate the consequences these alterations might have on their reproduction. Materials/Methods: High resolution karyotyping was carried out on 243 males undergoing treatment for reproduction problems in our clinic. They comprised carriers of anomalies of sexual chromosomes (14) (group 1), reciprocal translocations (38) (group 2), Robertsonian translocations (54) (group 3), inversions (13) (group 4), marker chromosomes (5) (group 5), heterochromatin polymorphisms (40) (group 6) and acrocentric polymorphisms (79) (group 7). The parameters evaluated were: sperm concentration, motility and morphology; recovery of capacitated spermatozoa; fertilization rate, fertilization failure, implantation failure; number of previous pregnancies, miscarriages, spontaneous pregnancies, cycles of assisted reproduction, biochemical pregnancies, ectopic pregnancies and newborn babies. Statistical analysis of the chosen variables was performed using analysis of variance (ANOVA) for those variables with normal distribution and the Kruskal-Wallis test for the remainder (significance P < 0.05). Results: Male carriers of sexual chromosome alterations present significantly lower sperm concentration, motility and morphology than males in the other groups. The least affected group regarding sperm morphology are those with chromosomal inversions. The highest fertilization rate was observed in the group of males with reciprocal translocations. The most affected group was the miscarriage patients in whom reciprocal translocations, inversions and marker chromosomes were found. Those with Robertsonian translocations and polymorphisms (groups 6 and 7) were less affected. The difference between the group with reciprocal translocations compared with the polymorphism groups was significant. For the other parameters we did not find significant differences. Conclusion: Numerical and structural alterations that affect the sexual chromosomes disturb the different seminal parameters more than other chromosomal anomalies. The highest miscarriage rate is observed in carriers of reciprocal translocations. The clinical pregnancy and live birth rates do not differ between groups; therefore, treatment by ART and PGD when required, appears to be the best reproductive option for male carriers of chromosomal alterations. [ABSTRACT FROM AUTHOR]

Culture media supplemented with reproductive fluids (RF) have been used in livestock species, improving the efficiency and quality of in vitro produced embryos. However, usefulness in humans is still unknown. In this study, we collected human reproductive fluids (HRFs) ex vivo (from 25 patients undergoing abdominal hysterectomy plus bilateral salpingectomy) and in vivo (from 31 oocyte donors). Afterward, protocols to evaluate their osmolality, pH, total protein concentration, endotoxin level, and sterility were optimized, establishing security ranges for their use as natural additives. In addition, a functional assay was developed with bovine embryos grown in vitro in a medium supplemented with 1% of collected HRFs. Finally, a proof of concept was performed with six patients on post ovulation day 2 to evaluate the full-term viability of embryos grown in media supplemented with autologous uterine fluid, collected under in vivo conditions. Two of the embryos resulted in successful pregnancy and delivery of healthy babies. In conclusion, this study establishes a complete quality control sheet of HRFs as additives for embryo culture media and shows first preliminary data on obtaining healthy offspring derived from embryos grown in media supplemented with HRFs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MH declared a past collaboration with one of the authors PC., (Copyright © 2021 Canha-Gouveia, Prieto-Sánchez, Sánchez-Ferrer, Mollá, Martínez-Soto, París-Oller, Soriano-Úbeda, Landeras and Coy.)

Purpose: The plasminogen/plasmin system is an important extracellular protease system whose function has been implicated in male reproductive function. However, its clinical relevance to fertility in human assisted reproduction technologies has not been systematically investigated. Here, we examined whether total and active populations of urokinase-type plasminogen activator (uPA) in human seminal plasma and spermatozoa are predictive of pregnancy outcome in couples undergoing insemination or intracytoplasmic sperm injection (ICSI)., Methods: Seminal samples from 182 men, 5 donors, 21 patients attending the clinic for infertility screening, and 156 for assisted reproduction technology (ART) treatment (insemination and ICSI), were evaluated. Total uPA in seminal plasma and spermatozoa as well as active uPA in seminal plasma were measured by ELISA. Sperm quality parameters and fertility outcomes following insemination or ICSI were correlated with the uPA values., Results: Active uPA in seminal plasma was positively correlated to the volume of the ejaculate, total number of spermatozoa in the ejaculate, and total motility. However, these values were not prognostic of fertility outcomes. Total uPA in spermatozoa was inversely related to sperm concentration, total sperm in ejaculate, morphology, and total and progressive motility, and this measure was not related to fertility. Importantly, however, higher values of total uPA in seminal plasma were detected in cases that resulted in pregnancy compared to those that did not follow insemination and ICSI treatment., Conclusions: Taken together, these findings lay the foundation for further understanding the mechanism by which total uPA in seminal plasma affects fertility and how this marker can be used as a predictor of ART outcomes.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women and the main cause of infertility due to anovulation. However, this syndrome spans the lives of women affecting them from in-utero life until death, leading to several health risks that can impair quality of life and increase morbidity and mortality rates. Fetal programming may represent the beginning of the condition characterized by hyperandrogenism and insulin resistance which leads to a series of medical consequences in adolescence, adulthood, and old age. Menstrual and fertility problems evolve into metabolic complications as age advances. An early and precise diagnosis is important for an adequate management of PCOS, especially at the extreme ends of the reproductive lifespan. However, many different phenotypes are included under the same condition, being important to look at these different phenotypes separately, as they may require different treatments and have different consequences. In this way, PCOS exhibits a great metabolic complexity and its diagnosis needs to be revised once again and adapted to recent data obtained by new technologies. According to the current medical literature, lifestyle therapy constitutes the first step in the management, especially when excess body weight is associated. Pharmacotherapy is frequently used to treat the most predominant manifestations in each age group, such as irregular menses and hirsutism in adolescence, fertility problems in adulthood, and metabolic problems and risk of cancer in old age. Close surveillance is mandatory in each stage of life to avoid health risks which may also affect the offspring, since fetal and post-natal complications seem to be increased in PCOS women.

The purpose of this study was to evaluate the effect of docosahexaenoic acid (DHA) dietary supplementation on semen quality, fatty acid composition, antioxidant capacity, and DNA fragmentation. In this randomized, double blind, placebo-controlled, parallel-group study, 74 subjects were recruited and randomly assigned to either the placebo group (n=32) or to the DHA group (n=42) to consume three 500-mg capsules of oil per day over 10 weeks. The placebo group received 1,500 mg/day of sunflower oil and the DHA group 1,500 mg/day of DHA-enriched oil. Seminal parameters (semen volume, sperm concentration, motility, morphology, and vitality), total antioxidant capacity, deoxyribonucleic acid fragmentation, and lipid composition were evaluated prior to the treatment and after 10 weeks. Finally, 57 subjects were included in the study with 25 in the placebo group and 32 in the DHA group. No differences were found in traditional sperm parameters or lipid composition of the sperm membrane after treatment. However, an increase in DHA and Omega-3 fatty acid content in seminal plasma, an improvement in antioxidant status, and a reduction in the percentage of spermatozoa with deoxyribonucleic acid damage were observed in the DHA group after 10 weeks of treatment.

The endometrium is one of a number of factors involved in achieving optimal outcomes after assisted reproductive treatment. Owing to its "passive" growth following adequate ovarian stimulation, it has received virtually no attention. Only when either endometrial thickness or ultrasonographic pattern seem inadequate have different strategies been assessed to try to improve it, especially in those cases where it seems difficult or impossible to make it grow. The objective of this review is to summarize the different strategies that have been investigated in patients with inadequate endometrium, to attempt to provide solid evidence of therapies that may be beneficial and to move away from empirism. A review of the existing literature was performed by searching MEDLINE, EMBASE, Cochrane library and Web of Science for publications in English related to refractory endometrium. Most current treatments are based on anecdotal cases and not on solid data, although worldwide many doctors and patients use them. In conclusion, this review found that it is not easy to provide a pragmatic, evidence-based approach to help physicians and patients confused by the available data on how to improve a poor endometrium. Honest balanced information provided to our patients is the best that we can do., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Question: Is there an association between blastocyst collapse patterns and implantation potential?, Summary Answer: Embryos that exhibit collapse are as likely to hatch as those that do not, but are less likely to implant and should not be replaced if alternatives are available., What Is Known Already: Studies of blastocyst collapse in different species of mammals have found that most blastocysts, that experience consecutive weak contractions, hatch successfully whereas those that exhibit strong contractions or collapse, fail to hatch., Study Design, Size, Duration: Retrospective cohort study. Seven hundred and fifteen transferred blastocysts were analyzed from July 2012 to May 2013., Participants/materials, Setting, Methods: University-affiliated infertility center. Participant patients were recipients of oocyte donation and autologous IVF cycles (n = 460). Embryo development was analyzed with a time-lapse imaging system. Variables studied included blastocyst collapse (defined as the separation of ≥50% of the surface of the trophectoderm of the blastocyst from the zona pellucida), kinetic variables, embryo morphology, implantation and clinical pregnancy rates., Main Results and the Role of Chance: A total of 139 blastocysts presented collapse (19.4%), of these 8 presented 2 collapses and 2 presented 3 collapses. The timings of embryo cleavages and the time taken to reach the morula stage and blastulation were significantly shorter in embryos with collapse than in those without. Implantation rates were compared in cycles where either all or none of the embryos replaced, implanted so that implantation data were known for every embryo. Among 408 embryos without collapse and 94 embryos with at least one collapse (94) the implantation rates were 48.5% (95% confidence intervals (CI) 46.7-53.4%) and 35% (95% CI 25.3-44.9%), respectively. The percentage of embryos that hatched was similar in both groups 28.7 and 31%, respectively., Limitations, Reasons for Caution: The retrospective nature of the study limits its potential value., Wider Implications of the Findings: Study the collapse pattern of the blastocyst, may assist selection of the blastocysts most likely to implant and increase IVF/ICSI success rates., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

There is a lack of information about the importance of fatty acid composition of the human sperm membranes and seminal plasma in the cryopreservation procedure. Our aims were to study the possible relationships between the fatty acid composition of human spermatozoa or seminal fluid before freezing, and the sperm quality, measured in terms of viability and motility, before and after freezing-thawing. A further objective of this study was to determine whether the antioxidant capacity (TAC) of the seminal plasma is related to fatty acid (FA) composition and to success of the cryopreservation process. Polyunsaturated fatty acids (PUFA), ω3 PUFAs and docosahexaenoic acid (DHA) in spermatozoa were significantly positively correlated with sperm viability and motility parameters before and after freezing. An inverse relationship was found for monounsaturated (MUFA), ratio ω6/ω3, ratio saturated saturated fatty acids/PUFA (SFA/PUFA) with the seminal parameters. Seminal plasma fatty acid composition was not related to viability. However, motility parameters before and after freezing were related to stearic acid (C18:0) and DHA. TAC in seminal plasma was directly related to PUFA, w3 and DHA. On the other hand, SFA, C22:0, C24:0 and MUFA in seminal plasma were inversely related to the antioxidant capacity. TAC was directly correlated with motion parameters after thawing, We described a significant correlation between the fatty acid composition of the human spermatozoa or seminal plasma and the sperm parameters of the samples after thawing. PUFA, W3 and specially DHA are directly correlated with sperm motility and viability after freezing/thawing, and MUFA was inversely correlated. This means that in the future the fatty acid composition could be used as a predictor of the capacity of cryopreservation. On the other hand, we could design further procedures to modify the lipid composition or/and antioxidant capacity of ejaculate to make it more resistant to the cryopreservation process., (© 2012 American Society of Andrology and European Academy of Andrology.)

In this study, we evaluated the effects of the thawing methodology on sperm function after cryopreservation in pellets. We compared the use of two thawing procedures: method (1) maintaining pellet for 10 min in air at room temperature, then another 10-min period in air at 37°C followed by dilution in a thawing medium; and method (2) immersing the pellets directly in thawing medium at 37°C for 20 min. This procedure leads to a higher rate of temperature increase and a dilution of the glycerol present in the freezing medium. We analyzed the effect of the thawing procedure on sperm motility, viability, membrane lipid packing disorder, acrosome status, reactive oxygen species (ROS) level and sperm chromatin condensation. This study revealed a positive effect of the M2 thawing methodology on sperm parameters. The percentage of spermatozoa with fast-linear movement is increased (M1: 17.26% vs. M2: 28.05%, p<0.01), with higher viability (M1: 37.81% vs. M2: 40.15%, p<0.01) and less acrosome damage (M1: 40.44% vs. M2: 35.45%, p=0.02). We also detected an increase in the percentage of viable spermatozoa with low membrane lipid disorder (M1: 31.36% vs. M2: 33.17%, p=0.03) and a reduction in chromatin condensation (44.62 vs. 46.62 arbitrary units, p=0.02). Further studies will be necessary to evaluate the possible clinical applications., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability., Methods: A randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 microg/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17-21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset < or =9 days after hCG administration) in 182 IVF patients with > or =20 but less than 30 follicles > or =10 mm., Results: The incidence of moderate/severe early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4% (1/26) in the quinagolide 50, 100 and 200 microg/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09-0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10-0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide., Conclusions: Quinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability. ClinicalTrials.gov Identifier: NCT00329693.

In our series, a very high prevalence of chromosomal abnormalities was observed in spontaneous miscarriages, irrespective of how pregnancy was achieved, by assisted reproductive technology (ART) or natural conception. This high prevalence was equally represented in both groups, with no statistical difference in type of chromosomal abnormalities or in total frequency; however, the incidence of monosomy X is increased and the polyploidies are decreased in abortus after intracytoplasmic sperm injection (ICSI) when it is compared with miscarriages after spontaneous gestations., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis., Methods: A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled., Results: Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67-2.91)., Conclusions: Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

Purpose: The objective of this study was to evaluate the effect of men and recipient age on the reproductive outcome of our oocyte donation program., Methods: We retrospectively analyzed 915 cycles, taking into account men and recipient age, separately and together., Results: The significant cut off value for men and recipients age with incidence in the reproductive outcome was 39 years. Recipient older than 38 years presented a significantly lower pregnancy and implantation rates than others (44.92 vs. 55.75 +/- 1.53%, 25.66 vs. 32.79 +/- 1.64%). If men age was older than 38, a significant reduction in pregnancy and implantation rates was observed, too (46.0 vs. 54.65%, 26.00 +/- 1.52 vs. 32.43 +/- 1.65%). When men and recipient age was analyzed together, a reduction in pregnancy and implantation was detected only if both were older than 38., Conclusions: Present study suggests that age has a detrimental effect on the reproductive outcome of oocyte donation cycles when both men and recipient are > or = 39 years old.

Intercourse during an IVF cycle has the potential to improve pregnancy rates since exposure to semen is reported to promote embryo development and implantation in animals. Conversely, coitus-induced uterine contractions or introduction of infection may have a detrimental effect. A multicentre prospective randomized control trial was conducted to determine if intercourse during the peri-transfer period of an IVF cycle has any influence on pregnancy success. Participants undergoing thawed embryo transfer (Australian centre) or fresh embryo transfers (Spanish centres) were randomized either to abstain or to engage in vaginal intercourse around the time of embryo transfer. The transfer of 1343 embryos during 478 cycles of IVF resulted in 107 pregnancies (22.4%), with 125 viable embryos remaining by 6-8 weeks gestation. There was no significant difference between the intercourse and abstain groups in relation to the pregnancy rate (23.6 and 21.2% respectively), but the proportion of transferred embryos that were viable at 6-8 weeks was significantly higher in women exposed to semen compared to those who abstained (11.01 versus 7.69 viable embryos per 100 transferred embryos, P = 0.036, odds ratio 1.48, 95% confidence interval 1.01-2.19). Hence exposure to semen around the time of embryo transfer increases the likelihood of successful early embryo implantation and development.

Recent investigations have pointed to a high prevalence of Y chromosome submicroscopic deletions in men with severely impaired spermatogenesis. We report on the incidence in 128 infertile men, in whom karyotype, sperm count, and hormonal parameters were evaluated. Patients with abnormal karyotype (other than an abnormal Y chromosome) or sperm concentration of more than 2 million/mL were excluded. Genomic DNA was extracted from the peripheral leukocytes of 57 men with azoospermia and 71 with severe oligospermia. Molecular analysis was performed by 3 multiplex polymerase chain reactions using a set of 9 sequence tagged sites (STSs) from 3 different regions of the Y chromosome: AZFa, AZFb, and AZFc. In 7% of the studied patients Yq microdeletions were detected, with a high prevalence in men with azoospermia (14%). No deletions were detected in the AZFa region. Deletions were present in AZFb, AZFc, or both regions. The deletion observed in 1 patient that did not overlap with the DAZ region demonstrates that genes other than DAZ may also be involved in the pathogenesis of some subsets of male infertility. Furthermore, common Yq deletions present different testicular pictures, suggesting that some unknown factors may be disturbing spermatogenesis. Because men with severe infertility suffer a high risk of Y chromosome deletion, screening for these men is recommended prior to treatment with assisted reproduction.

Objective: To evaluate prospectively the incidence of early pregnancy losses (before menstruation occurs) in IVF and ovum donation cycles., Design: Prospective case-control study., Setting: Tertiary care, university-associated center., Patient(s): One hundred forty-five patients undergoing IVF and 92 undergoing oocyte donation were recruited. The control group for IVF consisted of 15 ovum donors who had no ET and were instructed to avoid intercourse. The control group for oocyte donation included 10 women undergoing a mock cycle of steroid replacement., Intervention(s): Starting on day 6 after ET, the women were instructed to collect the first urine sample of the day every 2 days. Each patient collected six different specimens of urine (days 6, 8, 10, 12, 14, and 16 after ET for cases or the same days without ET for controls., Main Outcome Measure(s): beta-HCG was measured with a standardized microparticle enzyme immunoassay, and IVF reproductive outcome was assessed., Result(s): For IVF, positive implantation was registered in 88 of 145 cycles of embryo replacement (60.7%). Only 30 (20.7%) resulted in viable pregnancies, whereas the remaining 58 miscarried. Forty-two of these miscarriages (72.4%) were early pregnancy losses and 13 (22.4%) were classified as clinical abortions. In ovum donation, positive implantation was recorded in 64 of 92 cycles of ET (69.6%). A total of 30 (32.6%) ended in viable pregnancies, whereas the remaining 34 (37.0%) were miscarriages. Early pregnancy loss accounted for 70.6% of pregnancy losses, whereas biochemical pregnancies and clinical abortions accounted for 11.8% and 17.6%, respectively., Conclusion(s): Our results demonstrate that patients undergoing assisted reproductive technology have an increased rate of early pregnancy loss compared with fertile patients. In addition, these data indicate that implantation is more frequently impaired in IVF than in oocyte donation cycles, resulting in a high incidence of early pregnancy loss. This suggests that implantation may be subjected to abnormal conditions in assisted reproduction.

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.