The COVID-19 pandemic has brought new challenges to infertile couples: the fear and uncertainty of potential SARS-CoV-2 infection effects during pregnancy. The present study aims to evaluate depression, anxiety and stress parameters in pregnant women conceived by IVF, during the coronavirus outbreak. This prospective cohort study included 109 clinical pregnant women (fetal heart beat) that consecutively underwent embryo transfer after an IVF treatment during the coronavirus outbreak between Jun/20 to Feb/21 in a private ART (assisted reproductive technology) clinic. Patients were evaluated through telephonic interview at the end of each trimester of pregnancy (12, 24 and 34 weeks) by the DASS-21 questionnaire, an internationally validated scale to track the severity of depression, anxiety and stress symptoms. Clinical variables such as age, obstetric history, clinical comorbities and years of infertility were also included. Comparison statistical tests were applied accordingly to normal distribution of values. A p value <0,05 was considered significant. The mean age was 38,97±5,02 years old. The majority of patients had never been pregnant before (67%) and had no other comorbid associated (75,2%). The mean infertility time was 3,76±2,38 years. Singleton pregnancies represented 83,5%. During the follow-up, two patients had late miscarriage at 21 weeks of singleton pregnancies (1,8%) and one had a fetal demise at 26 weeks of a singleton pregnancy (0,9%). Four patients (3,7%) had very preterm labor (between 28-32 weeks), seven (6,4%) had moderate preterm labor (between 33-35 weeks) and one (0,9%) had a late preterm labor (36th week). In general, there were no difference in any of the emotional aspects evaluated (depression, anxiety and stress) along first, 2nd and 3rd trimesters (p=0.13, p=0.93 and p=0.55, respectively). However, when participants were separated by groups of age (<38 yo and ≥38 yo, means 34,84±2,90 and 42,35±3,69, p=0.007), older patients presented higher levels of stress (p=0.017) compared to the youngers. Furthermore, patients with history of previous pregnancy loss presented higher levels of anxiety and stress (p=0.037 and 0.036 respectively) compared to the nulliparous. In addition, when comorbidities were associated with infertility, patients also presented higher levels of anxiety and stress (p=0.03 and 0.002, respectively). Years of infertility (≤3 or ˃3 years) was not associated with aggravation in DASS scores during pregnancy. Our data demonstrated that patients who conceived during the pandemic by IVF showed higher levels of anxiety and stress throughout their pregnancy, as assessed by the DASS-21 scale, mainly if they are greater than 38yo, had previous pregnancy loss or presented other comorbity associated.
Endometrial microbiota may vary with infections and sexual routine besides ethnicity and habits. Chronic endometritis is known to produce a negative impact on reproductive outcomes. The aim of this study is to investigate the endometrial microbiota and chronic endometritis profiles in IVF patients and verify their reproductive outcomes after following an intravaginal probiotic supplementation and/or antibiotic administration, according to a commercial screening test provider.
The purpose of this study is to verify if morphokinetic parameters, according to maternal age subgroups, may predict blastocyst ploidy and clinical pregnancy. Retrospective cohort study with 260 autologous PGT-A cycles (NGS) performed from Dec-2017 to Dec-2019. Morphokinetics parameters (time of pronucleous fading - tPNf, time to 2-cell - t2, t3, t4, t5, t8 and time to blastulation - tB) and ploidy status were analyzed from blastocyst embryos cultured in a time-lapse incubator (Embryoscope Plus) according to maternal age subgroups: under 37 years old – yo (group 1, n=69 patients, 230 embryos), and between 37 and 42 yo (group 2, n=191 patients, 593 embryos). Euploid blastocysts transferred with ongoing clinical pregnancy were also analyzed (178 embryos/153 patients). Fisher and t tests were used as appropriate. As expected, euploidy rate is higher in patients <37 yo (63% versus 38% [37- 42yo], p<0.0001). Morphokinetic parameters between euploid and aneuploid embryos were distinct in younger patients (g1) at tB (107,01±10,11 vs 112,22±11,35 hours, p=0.0004) and in older patients (g2) at tPNf and tB (23,55±2,94 vs 24,07±3,27 hours, p=0.0406; 108,21±9,94 vs 111,21±11,51 hours, p=0.0003). Both tPNf and tB in euploid and aneuploid embryos had similar values between g1 and g2, showing these differences are related to ploidy status rather to maternal age. Maternal age was similar between euploid and aneuploid embryos in each group (g1: 34,42±2,28 vs 34,81±2,12, p=0.1497; g2: 39,34±1,46 vs 39,57±1,45, p=0.0704). Clinical pregnancy according to maternal age was similar between groups (g1: 43% positive [n=24], 57% negative [n=32]; g2: 56% positive [n=68], 44% negative [n=54], p=0.1458). Morphokinetic parameters of embryos from g1 patients that achieved clinical pregnancy were significantly earlier at tPNf, t3, t5, t8 and tB when compared to embryos that did not achieve clinical pregnancy (22,58±1,74 vs 25,03±2,83, p=0.0030; 36,51±2,74 vs 38,32±3,64, p=0.0228; 49,25±5,17 vs 53,22±6,91, p=0.0139; 56,79±8,68 vs 65,12±9,52, p=0.0013; 103,35±6,92 vs 109,30±10,43 hours, p=0.0191). Surprisingly, none morphokinetic parameter was significantly different between positive and negative clinical pregnancy in the g2 patients. Comparing the parameters between g1 and g2, almost all morphokinetics time-points (tPNf, t2, t3, t5 and t8) occurred in a later time-point in negative clinical pregnancy in younger patients compared to g2. In positive clinical pregnancy, tB was earlier in younger patients. While tB distinguished ploidy status in both age subgroups, morphokinetic parameters were only different for positive and negative clinical pregnancy for younger patients (<37yo). These results highlighted the importance of considering maternal age when analyzing morphokinetic parameters.
Methods: This is a cohort study, conducted at a university-based reproductive medicine center and private reproductive medicine center that aimed to evaluate granulosa cumulus cell gene expression in the insulin signaling pathway in Polycystic Ovary Syndrome (PCOS) patients undergoing in vitro fertilization (IVF) treatment and to compare the cumulus gene expression between normal weight and obese women without clinical insulin resistance. Fifteen PCOS patients, nine normal weight patients and six obese patients presenting normal HOMA IR (Homeostasis Model Assessment–Insulin Resistance), participated. Patients underwent oocyte retrieval for IVF and after the procedure, granulosa cumulus cells were removed from the oocytes for RNA extraction. Quantitative polymerase chain reaction (PCR) array analysis of 84 genes from insulin signaling pathway was conducted. The results were expressed as fold up- or fold down-expression in obese patients compared with normal weight patients. Any fold change ⩾3 or ⩽3 and any p ⩽ 0.05 were considered statistically significant. Results: There were 10 genes that were overexpressed in obese compared with normal weight women, BCL2L1, BRAF, CBL, DOK1, FBP1, FRS2, MTOR, PCK2, RPS6KA1, and SORBS1, that had a fold change ⩾3 and p ⩽ 0.05. Discussion: In the obese group, the overexpressed genes are mainly responsible for the proliferation and differentiation of cumulus cells during oocyte maturation, insulin resistance, apoptosis regulation, and glucose metabolism during early embryogenesis, suggesting that in the follicular environment, insulin resistance is present even in the absence of clinical signs. Conclusion: Together, our findings and the related literature suggest that those alterations may be associated with the worse prognosis of follicular development and oocyte maturation observed in PCOS obese women.
Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.
Objective: To identify the main research interests of Brazilian patients in the field of infertility and assisted reproductive technology (ART) treatments. Methods: This prospective multicenter cross-sectional study was carried out in Brazil. Patients attending five fertility centers from the Huntington Group between October and December 2018 were invited to join the study, which consisted of answering an anonymous survey online. Two hundred and twenty-seven patients signed the informed consent form and were emailed the survey link. The survey was designed based on the James Lind Alliance Priority Setting Partnership protocol. In the area of infertility, patients were probed on issues such as somatic and psychological effects of treatment, prevention, assisted reproductive technology (medications and procedures), success rates, risks, and emotional aspects. Results: The response rate (RR) was 47.58% (108 patients; 88 women - RR 51.46% and 20 men - RR 35.71%). Patient mean age was 36.5 years (SD 4.6). The top ten research priorities listed were 1) short- and long-term side effects of treatment; 2) how to cope with infertility; 3) risks associated with ART; 4) success rates in ART; 5) impact of diet on ART and fertility; 6) healthy habits; 7) alternative therapies; 8) impact of exercise on fertility and ART success; 9) oocyte quality and ovarian reserve; and 10) genetic or inherited causes of infertility. Conclusion: To better cater to the needs of patients and develop patient-centered care in the field of infertility and ART treatment, clinicians, healthcare providers, and the scientific community must identify patient concerns and priorities and make efforts to address them.
Differences on male and female metabolism and kinetics have been reported in early embryo development. However, there is still no consensus regarding the influence of sex on embryo's morphokinetics parameters, although recent studies pointed differences in morphokinetics markers for reproductive outcomes. We aimed to investigate if the embryo sex affects morphokinetics and implantation rates in euploid transfers and if those parameters are related to clinical pregnancy rates. Retrospective cohort study (December 2017 to December 2019), analyzing morphokinetic parameters collected from a time-lapse system from 482 euploid embryos. Embryo transfers and clinical pregnancies were followed up. Patients with clinical indication to IVF treatment and blastocyst biopsy (NGS platform) were included (n=257). All oocytes retrieved were fertilized by ICSI and cultured in a time-lapse system (Embryoscope Plus, Vitrolife). Euploid embryos were morphologically graded according to Gardner's system and also followed morphokinetic parameters on time of pronucleous fading (tPNf), time to 2-cell(t2), time to 3-cell (t3), time to 4-cell (t4), time to 5-cell (t5), time to 8-cell (t8) and time to blastulation (tB). Chi-square or t-test were used for statistical analysis. From 482 reported euploid blastocysts, 240 were male (49,8%) and 242 females (50,2%). Maternal age was similar between male and female groups (38,13±3,62 versus 38,40±3,78, p=0.3009). Analysis of morphokinetics parameters revealed that at t8, male embryos were faster than females (58,61±9,93 versus 59,85±8,89, p=0.0349). Other morphokinetic parameters analyzed were similar between genders. Two-hundred twenty-seven embryos were transferred and had known implantation outcomes. Clinical pregnancy rates were similar between male and female (48,8% versus 56,8%, p=0.2329). Maternal age in positive and negative clinical pregnancy were similar between genders (male: 38,30±2,90 versus 38,47±2,95, p=0.8705 and female: 38,55±3,38 versus 38,19±4,72, p=0.7078, respectively). Morphokinetics parameters in positive and negative clinical pregnancy in male embryos were not statistically different. However, in female blastocysts, clinical pregnancy was correlated with faster t5 and t8 (t5: 48,84±6,30 versus 50,95±6,95, p=0.0416 and t8: 57,01±7,20 versus 62,22±10,15, p=0.0029, respectively). Morphology grades between male and female embryos were not different between good quality embryos (grades A and B – 80% versus 76%) and poor quality embryos (at least one grade C – 20% versus 24%, p=0.2736). Our results showed that euploid male blastocysts are faster at t8, however the clinical pregnancy rate is correlated to t5 and t8 only for female euploid embryos. The morphokinetic parameters, as a tool for embryo selection, is an increasing demand in IVF routine mainly after the time-lapse technology's implementation. The differences in morphokinetics between male and female blastocysts must be taken into consideration at the time of selection of the embryo with best potential of clinical pregnancy.
Objective: This study seeks to identify the role and possible participation of a psychologist/psychoanalyst inside an Oocyte Pick-up Room and a Recovery Room (OPR-RR) in an Assisted Reproduction clinic and the implications on patients and team.Methods: Prospective study of psychological support during the procedures from September 2014 to December 2018.Most visits took place during oocyte retrievals, for either IVF/ICSI or gamete freezing.Results: Of the total of 2,343 cases, the psychologist was present in 965 of them (41%), during oocytes retrievals, with available professionals in 59% of the times (722 cases).The embryo transfers (1,011) had psychological assistance in 20% of the times (218 cases).The intrauterine insemination cases were excluded for not happening in a surgical environment.The recovery room was identified as one of the spaces for welcoming and listening to anxieties, desires, projects, worries, fears, frustrations, joys and expectations of those who come to the clinic seeking the desire to gestate.The patients' talks, collected in observations transcribed from what was heard, with dates and types of procedures, were discussed with either the team or the assistant physician.The team stands positively in the presence of a psychologist/psychoanalyst, who brings new perceptions and the development of the whole art of listening, for all involved. Conclusion:The presence of a psychologist/psychoanalyst in the Oocyte Pick-up Room and the Recovery Room in an Assisted Reproduction clinic means an opportunity to listen to patients' emotions, providing well being to patients and echoing in the teamwork relationships.
Objective: To compare the results of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles in women with good prognosis, when they were electively transferred, a blastocyst stage embryo (group 1) versus a blastocyst stage and a mórula stage embryo (group 2).Methods: 35 transfers from January/2014 to January/2018 were included, these occurred in na assisted reproduction center.Selection criteria: Patients in first or second treatment for IVF/ICSI less than 35 years old, with body mass index <30kg/m 2 who used their own oocytes with normal ovarian reserve (baseline of antral follicles ≥11) and recipients without age restriction.Cases of severe male fator (spermatic concentration below 1million/ml) were excluded.The transfer was realized on fifth day of embryonic development.Luteal phase support was performed with micronized progesterone 600mg/day vaginally and estradiol 6mg/day orally, started the day after eggs collection.The receivers used 6mg/day of estradiol valerate orally, beginning on first day of menstrual cycle and 600mg/day of micronized progesterone, vaginally, for five days before embryo transfer.Were evaluated: mean age of women under 35 years who used their own oocytes and donors; pregnancy rate (βHCG positive); pregnancy loss rate and ongoing pregnancy rate (fetus alive at 12th week of pregnancy).Results: Between group 1 (n=24) and 2 (n=11), mean age of women under 35 who used their own oocytes were 33(±1.6)and 31(±1.8)years old and for donors were 34(±0.5)and 29(±0) years old, for both groups, respectively.Pregnancy rate was 50% (12/24) for group 1 and 18% (02/11) for group 2 (p=0.02).Pregnancy loss rate was 17% (02/12) for group 1 and 50% (01/02) for group 2 (p=0.07).Ongoing pregnancy rate was 42% (10/24) for group 1and 9% (01/11) for group 2 (p=0.01). Conclusion:The analysis of our data shows that transfer another embryo with a slower development with a blastocyst, with the intention of increase pregnancy rates, can actually worsen the results.There is a worldwide trend about extending embryo culture by fifth or sixth day, then these data should be validated in a larger number of cases.The reason for an embryo with slower development impact on development of another embryo with normal development should be evaluated.We emphasize that the results were extracted from cases with good prognosis and can not be extrapolated to other cases.
Objective The aim of this study was to assess the knowledge about the risk of infertility in cancer patients after treatment, and the options for fertility preservation based on a survey carried out during the 2013 Pink October campaign. Methods This survey was carried out during the 2013 Pink October event in the most important public park of São Paulo, Brazil. Approximately 900 people expressed interest in learning about breast cancer prevention and fertility preservation by participating in workshops, and 242 people filled out a questionnaire. Results Most of the respondents (78.5%) were women, and one-fourth (25%) had at least one relative with gynecological cancer. Among women over 40 years of age, 86.3% had been screened for breast cancer at some point. However, few participants (34.0%) were aware that cancer treatment can lead to infertility or had heard about fertility preservation options (22.0%). Having a relative with cancer did not influence their knowledge about fertility preservation (22.4% versus 21.3%; p=0.864). However, a higher educational level was significantly associated with more knowledge about the effects of cancer on fertility and options for fertility preservation. Conclusions The majority of participants did not have knowledge about the impact of oncologic treatment on fertility and did not know that there are options to preserve fertility in cancer patients. Awareness of infertility risk factors is an essential first step to safeguard future fertility, and therefore, more educational initiatives are needed to spread knowledge about oncofertility.
Because of scientific developments, life has been extended in recent decades, and among all diseases, cancer has gained a greater dimension and is recognized as a public health topic worldwide. There has been a major focus on breast cancer, which is recognized as the most common malignancy in women [1]. In 2012, there were an estimated 230,000 new cases of invasive breast cancer in the USA, mainly after menopause [2]. However, breast cancer at the reproductive age is considered a worst and invasive prognosis, for which chemotherapy using high doses of alkylating agents and radiotherapy with ionizing radiation should be applied. Such approach is known to reduce the primordial follicle reserve and cause premature ovarian failure, possibly with genetic damage to growing eggs [3]. Advances in reproductive techniques have provided many fertility preservation options [4]. However, initial trials on oocyte cryopreservation were limited by spindle misalignment and errors in the chromosomal arrangement due to ice formation inside the oocytes during the process [5]. In the last 15 years, a better understanding of the cryopreservation technique has resulted in improvements in the slow-freezing method and the introduction of the vitrification. Vitrification is the process of cryopreservation using ultra-rapid cooling at high concentrations of cryoprotectants, which avoids the formation of ice crystals [6]. The intracytoplasmic water is transformed into a glassy vitrified state, which thereby reduces cellular damage. This method has become recognized as a superior tool for oocyte cryopreservation [7]. In the present case report, we describe the outcome of a patient presenting breast cancer, who had her oocytes vitrified for 6 years and underwent in vitro fertilization (IVF) cycles that produced viable blastocysts and a successful healthy baby delivery.