A Pilot Analysis of Whole Transcriptome of Human Cryopreserved Sperm.

Sperm cryopreservation is a procedure widely used to store gametes for later use, to preserve fertility in patients prior to gonadotoxic treatments or surgery, and for sperm donation programs. The purpose of the study was to assess the impact of cryopreservation on human sperm transcriptome. Semen samples were collected from 13 normospermic men. Each sample was divided into two aliquots. The total RNA was immediately extracted from one aliquot. The second aliquot was frozen and total RNA was extracted after a week of storage in liquid nitrogen. The RNA samples were randomized in four pools, each of six donors, and analyzed by microarrays. The paired Significance Analysis of Microarray was performed. We found 219 lower abundant transcripts and 28 higher abundant transcripts in cryopreserved sperm than fresh sperm. The gene ontology analysis disclosed that cryopreservation alters transcripts of pathways important for fertility (i.e., spermatogenesis, sperm motility, mitochondria function, fertilization, calcium homeostasis, cell differentiation, and early embryo development), although the increase of some transcripts involved in immune response can compensate for the harmful effects of freezing.

Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.

BACKGROUND: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment-induced gonadotoxicity. PATIENTS AND METHODS: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the "biological window" of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). RESULTS: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33-42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56-2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45-2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01-0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. CONCLUSIONS: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.

Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum - a systematic review with implications for the function of the oxytocinergic system.

BACKGROUND: The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding. AIM: To systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems. METHODS: Systematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-five publications met inclusion criteria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables. RESULTS: Infusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32 mU/min) maternal plasma oxytocin reached 2-3 times physiological levels. Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher. Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus. CONCLUSIONS: Synthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2-3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct effects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may influence uterine blood flow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress.

Factors influencing the effect of external cephalic version: a retrospective nationwide cohort analysis.

OBJECTIVE: This study aims to assess the factors associated with the success and failure rate of the external cephalic version (ECV) in breech fetuses. Secondary outcomes were fetal presentation in labor and mode of delivery. METHODS: This cross-sectional study examined the live birth certificates from 2003 through 2020 from US states and territories that implemented the 2003 revision. A total of 149,671 singleton pregnancies with information about ECV success or failure were included. The outcome was ECV success/failure, while the exposures were possible factors associated with the outcome. RESULTS: The successful ECV procedures were 96,137 (64.23%). Among the successful ECV procedures, the prevalence of spontaneous vaginal delivery was 71.63%. Among the failed ECV procedures, 24.74% had a cephalic presentation at delivery, but 63.11% of these pregnancies were delivered by cesarean section. Nulliparity, female sex, low fetal weight centile, high pre-pregnancy BMI, high BMI at delivery, and high maternal weight gain during pregnancy were associated with an increased ECV failure (p < 0.001). African American, American Indian and Alaska Native race categories were significant protective factors against ECV failure (p < 0.001). Maternal age had a U-shape risk profile, whereas younger maternal age (< 25 years) and old maternal age (> 40 years) were significant protective factors against ECV failure (p < 0.001). CONCLUSIONS: A high prevalence of successful ECV procedures and subsequent spontaneous vaginal delivery were found. The present results found nulliparity, maternal race, maternal age, female fetal sex, low fetal weight, and maternal anthropometric features correlated to ECV results. These findings can potentially improve the knowledge about the factors involved in ECV, allowing more informed counseling to the women undergoing this procedure.

Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis.

PURPOSE: Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. METHODS: A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. RESULTS: Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12-1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80-1.77, p = 0.390). CONCLUSION: Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

Impact of the COVID-19 pandemic on voluntary terminations of pregnancy in an Italian metropolitan area.

PURPOSE: The COVID-19 pandemic and national lockdown from 9 March to 4 May 2020 changed social, familial, and sexual relationships, as well as how citizens interact with the health services. How these profound changes have affected sexuality, contraception and voluntary terminations of pregnancy is still largely undescribed. The main objective of this study was therefore to find out whether the COVID-19 pandemic and ensuing lockdown affected the demand for legal abortion. MATERIAL AND METHODS: The study period was divided into three phases: the pre-pandemic (January and February 2020); lockdown (March and April); and post-lockdown (May and June). The number and characteristics of women requesting pregnancy termination each month during that time were compared with the stats for the same months in the preceding three years (2017-2019). RESULTS: Immediately after national lockdown, the number of voluntary abortions markedly declined (-40.45%). The effect was more evident in women below 20 years of age (-66.67%), employed versus unemployed women (-42.71% vs. -21.05), and non-Italian versus Italian citizens (-53.01 vs. -32.85). No difference was found in the mean time from request to execution of the procedure, or in the type of the procedure used. CONCLUSION(S): National lockdown reduced the number of unwanted pregnancies, especially in younger women. The Italian health service's response to the demand appears to have been unaffected by the pandemic. However, as the demand for abortion is still high, probably due to unplanned pregnancies among cohabitants within a stable relationship, contraception guidance should be improved among women traditionally deemed low-risk in terms of sexual behaviour.

Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting.

BACKGROUND: Healthy individuals and patients with cancer who are carriers of germline pathogenic variants in the BRCA1/2 genes face multiple reproductive challenges that require appropriate counseling and specific expertise. MAIN BODY: On December 5th-7th, 2019, patient advocates and physicians with expertise in the field of reproductive medicine, fertility preservation, and oncology were invited to "San Giuseppe Moscati" Hospital in Avellino (Italy) for a workshop on reproductive management of women with germline pathogenic variants in the BRCA1/2 genes. From the discussion regarding the current evidence and future prospective in the field, eight main research questions were formulated and eight recommendations were developed regarding fertility, fertility preservation, preimplantation genetic testing, and pregnancy in healthy carriers and patients with cancer. CONCLUSION: Several misconceptions about the topic persist among health care providers and patients often resulting in a discontinuous and suboptimal management. With the aim to offer patient-tailored counseling about reproductive issues, both awareness of current evidences and research should be promoted.

Asymptomatic SARS-CoV-2 infections in pregnant patients in an Italian city during the complete lockdown.

Data from both New York and London report a high prevalence of the asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant patients admitted for delivery, raising questions on the possible correlated dangers (ie, contacts with healthcare workers; the possible creation of an intrahospital outbreak at birth; and conflicting evidence on vertical transmission). For this study, results from SARS-CoV-2 screening via nasopharyngeal swab from maternity wards of the four hospitals of Genoa, Italy, were collected during a month of complete lockdown from 1 April to 30 April 2020. Out of 333 tested women, only 9 were symptomatic. Only one symptomatic patient (0.3%) and six asymptomatic ones (1.8%) tested positive. Out of the six positive asymptomatic patients, five were from the most disadvantaged neighborhood of the city (assessed by postal code). In conclusion, even if Italy was badly affected by coronavirus disease 2019 in the studied month, the reported prevalence of SARS-CoV-2 infections in asymptomatic pregnant patients at term was lower than the ones reported in the literature.

Occurrence of smooth endoplasmic reticulum aggregates in metaphase II oocytes: relationship with stimulation protocols and outcome of ICSI and IVF cycles.

STUDY QUESTION: Is there any association between the appearance of smooth endoplasmic reticulum aggregates (SERa) in oocytes and ovarian stimulation, embryological, clinical and neonatal outcomes of ICSI and IVF cycles? SUMMARY ANSWER: A suboptimal prolonged ovarian stimulation is detrimental to oocytes by inducing the occurrence of SERa, which reduces the reproductive potential of oocytes. WHAT IS KNOWN ALREADY: Controlled ovarian stimulation recruits oocytes of different qualities. Based on current evidence, it was agreed that non-homogeneous cytoplasm may represent the normal variability among oocytes rather than a dysmorphism with developmental significance. The only exception is the appearance of SERa within the ooplasm. Owing to the lack of univocal evidence in this literature about the safety of injecting oocytes with SERa and the mechanism responsible for the occurrence of SERa, this topic is still a matter of debate. STUDY DESIGN, SIZE, DURATION: A retrospective, longitudinal cohort study performed at a tertiary level public infertility center. We included 1662 cycles (180 SERa+ and 1482 SERa-) from 1129 women (age: 20-44 years) who underwent IVF/ICSI treatments in 2012-2019. The SERa+ cycles had at least one SERa+ oocyte in the oocyte cohort. The SERa- cycles had morphologically unaffected oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected stimulation data and embryological, clinical, neonatal outcomes of SERa- and SERa+ cycles and oocytes. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 347 out of 12 436 metaphase II oocytes (2.8%) were affected by SER. We performed only 12 transfers involving at least one SERa+ embryo. Stimulation length (P = 0.002), serum progesterone (P = 0.004) and follicle size (P = 0.046) at trigger, number of retrieved (P = 0.004) and metaphase II (P = 0.0001) oocytes were significantly higher in SERa+ than SERa- cycles. Fertilization rate was significantly (P < 0.0001) reduced in SERa+ cycles and oocytes compared to SERa- counterparts. Embryos of SERa+ cycles had a lower blastocyst formation rate compared to embryos of SERa- cycles (P = 0.059). Statistical analysis according to a generalized estimating equation model performed at patient level demonstrated that the duration of ovarian stimulation was predictive of SERa+ oocytes appearance. The clinical success of SERa+ cycles was lower than SERa- cycles, although no differences in neonatal birthweights or malformations were recorded in sibling unaffected oocytes of SERa+ cycles. LIMITATIONS, REASONS FOR CAUTION: Given that SERa+ oocytes were discarded in our center for years and transfers of embryos originating from affected oocytes were generally avoided, clinical outcomes of SERa+ cycles are largely attributable to the transfer of embryos derived from unaffected oocytes of SERa+ cycles and we did not have data about newborns from affected oocytes, since none of the transfers involving SERa+ embryos resulted in a progressive clinical pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: For the first time, we speculate that the late-follicular phase elevated serum progesterone caused by a suboptimal prolonged ovarian stimulation may be detrimental to the oocytes by inducing the occurrence of SERa, resulting in negative effects on their reproductive potential. This raises the question of whether some stimulation regimens could be worse than others and a change in stimulation protocol would reduce the possibility of producing oocytes with suboptimal maturation. In particular, our data highlight the importance of correct timing of the trigger in order to maximize oocyte collection, not only in terms of numerosity but also their reproductive potential. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Menstrual cycle resumption and female fertility after autologous hematopoietic stem cell transplantation for multiple sclerosis.

Data on fertility after autologous hematopoietic stem cell transplantation (aHSCT) in women with multiple sclerosis (MS) are inconclusive. This study aims to report on post-aHSCT menstrual resumption in a multi-center MS-women cohort. Out of 43 women, 30 (70%) recovered menses after a mean time of 6.8 months. Older age (odds ratio (OR) = 0.5, p < 0.0001) and previous pulsed cyclophosphamide (OR = 0.44, p = 0.005) were independently associated with a reduced menstrual recovery probability. Conditioning regimens' intensity resulted not associated with post-procedure amenorrhea. Our results highlight younger age as significantly associated with menses recovery; proper fertility counseling for MS women candidated to aHSCT both prior- and post-transplantation is therefore warranted.

Pronuclear score improves prediction of embryo implantation success in ICSI cycles.

BACKGROUND: In assisted reproduction technology embryo competence is routinely evaluated on morphological criteria but efficacy remains relatively low. Additional information could be obtained by evaluating pronuclear (PN) morphology. Up to now controversial results have been reported about the prognostic value of PN score. One of the main limitations of literature data is the use of different PN classification methods. In this regard, in 2011 the ESHRE and Alpha Scientists in Reproductive Medicine defined three PN categories to standardize zygote assessment. In this study we evaluated whether the consensus ESHRE-Alpha system for the pronuclear scoring could be an useful additional criterion to improve prediction of embryo implantation potential. METHODS: This is a retrospective, longitudinal, observational, cohort study. We included 3004 zygotes from 555 women who underwent ICSI treatment at our Center between January 2014 and June 2019. The PN were categorized as score 1: symmetrical, 2: non-symmetrical, 3: abnormal. A subset of 110 zygotes did not cleaved. On day 2-3 1163 embryos were transferred, 232 arrested, and 9 were cryopreserved. Among the 1490 embryos cultured up to day 5-7, 516 became blastocysts: 123 were transferred on day 5 and 393 were cryopreserved. Comparisons of age, cleavage and blastocyst rate, quality of embryos, implantation success among PN score groups were evaluated by chi-square test or Kruskal-Wallis test as appropriate. Potential predictors of embryo implantation were first tested in univariable analysis using generalized estimating equations taking into account correlation between embryos originated from the same patient. Then, variables potentially associated with implantation success (P<0.05) were included in a multivariable analysis for calculating the adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: There was no significant difference in patients'age, cleavage and blastulation rates, and embryo morphology among the three PNscore groups. The PN score 1-embryos had a greater implantation success respect to score 2-3-ones (OR 1.83; 95% CI 1.34-2.50, P=0.0001). Consistently, the pronuclear score remained predictive of implantation in top quality embryos (OR 1.68; 95%CI 1.17-2.42, P= 0.005). CONCLUSIONS: The consensus pronuclear score may be routinely included among criteria for embryo evaluation to increase patients' chance of becoming pregnant.

Contraception in cancer survivors: insights from oncofertility follow-up visits.

OBJECTIVE: Current literature suggests that cancer survivors are less likely to receive adequate contraception counseling. However, limited data existed on barriers to contraception usage in this population and on the efficacy of dedicated consultations. This study aims to describe how contraception is perceived by cancer survivors after counseling and acceptance rates of highly effective contraceptives. METHODS: We retrospectively analyzed clinical records from 313 consecutive cancer survivors at their first follow-up visit at the Oncofertility Unit of a tertiary hospital, from 2014 to 2019. Contraception acceptance and choice were examined stratified for the type of malignancy (hormone-sensible or not). A multivariate logistic regression model was used to evaluate possible predictors of acceptance. RESULTS: Thity-three women were excluded from the analysis because trying to conceive or already pregnant. Out of the remaining 280, only 9 (3.2%) asked spontaneously for contraception, in all the other visits the issue was brought up by the physician. After counseling 44.3% of the women without contraindications still opted out effective methods for fear of hormones or refusal of more medications. Age < 33 years and being in a relationship were correlated with acceptance. CONCLUSIONS: Even after a complete counseling in a dedicated service, fears of hormones and refusal of more medications remain strong issues for these patients. Family planning needs to be discussed with cancer survivors, preferably in the context of a long-term healthcare relationship. The Oncofertility Unit should become a privileged place for this type of counseling.

Influence of age on response to controlled ovarian stimulation in women with low levels of serum anti-Müllerian hormone.

This study aims at detecting and evaluating differences in quantitative response to controlled ovarian stimulation (COS) with high doses of gonadotropins in women with low serum anti-Müllerian hormone (AMH). About 369 first cycles in a real-life scenario in women between 21 and 43 years old and with AMH ≤0.9 ng/ml were analyzed. Older women had a significantly worse outcome with respect to young women, not only qualitatively, but also in terms of quantitative ovarian response to COS [odd ratio (OR) to obtain at least three MII oocytes with each increasing year of female age: 0.89, 95% CI: 0.85 - 0.94; p < .001]. This study endorses that age is a significant factor when counseling patients with low AMH. AMH levels per se are not a reason to exclude patients from a COS treatment, since pregnancy and live birth can be achieved, especially in younger patients. However, with an AMH equally low, the ovarian response worsens with age, making questionable the effectiveness of a stimulation with high-dose gonadotropins in the older subgroup.

Non-invasive mitochondrial DNA quantification on Day 3 predicts blastocyst development: a prospective, blinded, multi-centric study.

In ART, embryo quality evaluation is routinely based on morphological criteria. We previously demonstrated that the mitochondrial DNA (mtDNA)/genomic DNA (gDNA) ratio in culture medium was significantly associated with embryo quality and viability potential. The purpose of this prospective, blinded, multi-centric study was to validate the use of mtDNA/gDNA ratio in Day 3 spent medium as a predictor of human embryo developmental competence. The mtDNA/gDNA ratio was assessed in Day 3 culture media (n=484) of embryos from 143 patients by quantitative PCR. A mixed effect logistic regression model was applied. We found that mtDNA/gDNA ratio in Day 3 culture medium combined with embryo morphology improves the prediction upon blastulation compared to morphology alone (P < 0.0001), independent of patient and cycle characteristics. With regard to routine use in clinics, we evaluated the ability of the novel, combined grading score to improve selection of developmentally competent embryos of a single cohort. Including embryos from 44 patients, the sensibility and specificity of the scoring system based on Day 3 morphological stage were 92% and 13%, respectively. Integration with the culture medium mtDNA/gDNA ratio increased the performance of the method (sensibility: 95%; specificity: 65%). The results of this study suggest the possibility of carrying out a non-invasive evaluation of embryonic mtDNA content through the culture medium. When combined with embryo morphology, it has the potential to help embryologists rank embryos and choose which embryo(s) has the greater development potential, and thus should be transferred on Day 3, among sibling embryos with the same morphological grade.

Beyond fertility preservation: role of the oncofertility unit in the reproductive and gynecological follow-up of young cancer patients.

STUDY QUESTION: Are there reasons that motivate young cancer survivors to ask for follow-up visits at an oncofertility unit? SUMMARY ANSWER: Cancer survivors request oncofertility follow-up visits for the management of treatment-related side effects or ovarian reserve evaluation, even if not (or not yet) wishing for a pregnancy. WHAT IS KNOWN ALREADY: Personalised oncofertility counselling before gonadotoxic therapies is considered standard of care for young women with newly diagnosed cancer. However, the long-term follow-up of these patients in an oncofertility unit is not described in the literature other than for the use of cryopreserved material. STUDY DESIGN, SIZE, DURATION: We retrospectively examined rates and reasons for the first follow-up visits of 154 consecutive young female cancer patients (age range: 18-40 years) who underwent a pre-treatment consultation between January 2012 and June 2017. Demographic and clinical data were collected, as well as information about the chosen fertility preservation method, if any. PARTICIPANTS/MATERIALS, SETTING, METHODS: Rates and reasons for follow-up visits were collected and expressed as percentages. Different reasons were examined in the whole cohort and stratified for type of malignancy. Possible predictive factors for return to the follow-up visit (age, nulliparity, presence of a partner, neoplasm, having cryopreserved material) were investigated through logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 154 patients, 74 returned to the oncofertility unit (48.1%) for a follow-up visit. The first visit was requested mostly at the end of anticancer therapies (51.3% versus 40.5% during therapies and 8.1% after cancer relapse). Among these patients, only 10.8% returned for the first time because they were actively desiring a pregnancy. For the others, the most common reasons for consultations were management of gynecological adverse effects of therapies (29.7%) and evaluation of ovarian reserve not linked to an immediate desire for a pregnancy (39.2%). Other patients asked for contraception (4.1%), menopause counselling (5.4%), or new fertility preservation counselling because of cancer relapse (10.8%). None of the examined factors were significantly predictive of return to the oncofertility unit. LIMITATIONS, REASONS FOR CAUTION: These findings represent the experience of a single centre. A longer duration of follow-up would be needed to provide more precise information on this regard. WIDER IMPLICATION OF THE FINDINGS: The role of an oncofertility unit should not be limited to proposing fertility preservation procedures. In the management of young adult cancer patients, the reproductive medical specialist should be considered a key figure not only before but also during and after anticancer treatments to explore salient aspects of gynecological and reproductive health. STUDY FUNDING/COMPETING INTEREST(S): This research did not receive any specific funding. M.L. served as a consultant for Teva and received honoraria from Theramex outside the submitted work. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N.A.

Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization.

This study aims to evaluate levels of anxiety and depression in women, correlated with infertility per se and with infertility treatments, highlighting predictors of higher levels of distress. Two validated standardized questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Fertility Quality of Life (FertiQoL), were administered to 89 women both before their first cycle of infertility treatment and again at the end of the ovarian stimulation for in vitro fertilization (IVF). Women's levels of anxiety were significantly higher before the treatment than during the treatment itself. Stratifying the women in three groups based on principal cause of infertility (male infertility, female infertility, or both male and female), we found significantly higher levels of anxiety and general distress in patients under treatment for female infertility. Higher anxiety levels in our sample before the treatment are probably an effect of not knowing what they are expected to do to solve their problem. Moreover, when the cause of infertility is exclusively female, women experience higher levels of anxiety and general distress both before and during the treatment, probably correlated to a sense of guilt. These data help the treating physician to better counsel patients and to provide a more focused psychological support.

A successful healthy childbirth and an ongoing evolutive pregnancy in a case of partial globozoospermia by hyaluronic acid sperm selection.

We here report a successful healthy childbirth and an ongoing evolutive pregnancy in a case of partial globozoospermia after selection of mature spermatozoa bound to hyaluronic acid (HA). The couple underwent two in vitro fertilisation (IVF) cycles. In the first attempt, 14 MII oocytes were retrieved. Randomly, seven oocytes were injected by conventional PVP-ICSI and seven by HA-ICSI. Fertilised oocytes were 2/7 and 4/7 after PVP-ICSI and HA-ICSI respectively. Transfer of two grade A embryos from HA-ICSI lead to birth of a healthy baby. The surplus embryo of the HA-ICSI group was vitrified at blastocyst stage. The two embryos from PVP-ICSI arrested their development. Two years after the childbirth, the vitrified blastocyst was transferred into the uterus, but implant failed. In the second cycle, 14 MII oocytes were retrieved and they were injected by HA-ICSI. Fertilised oocytes were 10 out of 14 injected oocytes. On day 5, two blastocysts were transferred into uterus and a single evolutive pregnancy is ongoing. On day 6, one blastocyst was vitrified. The remaining surplus embryos arrested their development. A healthy childbirth and an ongoing evolutive pregnancy in two consecutive ICSI attempts of the same couple suggest that HA sperm selection might assist in cases with partial globozoospermia.