Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation.

Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. This was a secondary analysis of gonadal hormone production, future infertility risk assessment, and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (interquartile range [IQR]) or percentages. There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 to 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3388 to 9706 mg/m2. The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent proxies (for patients <18 years old) and patients ≥18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty-five percent of parent proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. There are high rates of gonadal dysfunction post-HCT, but many parent proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.

The impact of sickle cell disease and its treatment on ovarian reserve in reproductive-aged Black women.

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80-2.76 vs. 4.12, 95% CI 3.11-5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43-76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist.

In-utero exposure to polybrominated biphenyl (PBB) and menstrual cycle function in adulthood.

BACKGROUND: There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood. METHODS: For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014). A total of 41 women who were born after the PBB contamination incident (1973-1974) and were prenatally exposed to PBBs, were included in this analysis. We estimated in-utero PBB exposure using maternal serum PBB measurements taken after exposure and extrapolated to time of pregnancy using a PBB elimination model. Women were followed for up to 6 months during which they provided daily urine samples and completed daily diaries. The urine samples were assayed for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). RESULTS: Women in our study were, on average, 27.5 (SD:5.3) years old and contributed 4.9 (SD:1.9) menstrual cycles of follow-up. Compared to women with low in-utero PBB exposure (≤1 ppb), women with medium (>1.0-3.0 ppb) and high (>3.0 ppb) exposure had higher maximum 3-day mean Pd3G levels during the luteal phase. Specifically, the age- and creatinine-adjusted maximum 3-day mean luteal phase Pd3G levels (95% CI) in increasing categories of in-utero PBB exposure were 9.2 (4.6,13.9), 14.8 (11.6,18.0), and 16.1 (12.9,19.3) µg/mg creatinine. There were no meaningful differences in average cycle length, follicular or luteal phase cycle length, bleed length, or creatinine-adjusted E13G or FSH levels by category of in-utero PBB exposure. CONCLUSION: Higher exposure to PBB in-utero was associated with increased progesterone levels across the luteal phase, however, most other menstrual cycle characteristics were largely unassociated with in-utero PBB exposure. Given our modest sample size, our results require cautious interpretation.

The use of fertility treatments among reproductive-aged women after cancer.

OBJECTIVE: To examine whether female cancer survivors are more likely to pursue care for infertility after cancer than women without cancer. DESIGN: Population-based cohort study involving detailed interviews regarding reproductive history. SETTING: Not applicable. PATIENTS: Female cancer survivors aged 22-45 years, who were at least 2 years after a cancer diagnosis between the ages of 20 and 35 years (n = 1,036), and age-matched comparison women with no cancer history (n = 1,026). EXPOSURE: History of cancer vs. no history of cancer. MAIN OUTCOME MEASURE(S): Each cancer survivor was randomly matched to a comparison woman, who was assigned an artificial age at cancer diagnosis equal to that of her match. Matching was repeated 1,000 times. Outcomes of visiting a doctor for help becoming pregnant or undergoing fertility treatment were modeled using Cox proportional hazards regression, comparing survivors after a cancer diagnosis to age-matched comparison women, adjusted for race, income, residence, education, and parity. RESULTS: Only 25.5% of cancer survivors reported meeting their desired family size before a cancer diagnosis. The median time from diagnosis to interview among survivors was 7 (interquartile range 5-11) years. Cancer survivors were more likely to report having no children (32.6%) at the interview compared with women with no cancer history (19.5%). Survivors were not more likely to visit a doctor for help becoming pregnant compared with women without a cancer history, matched on birth year and followed by the age at which cancer survivors received their diagnosis (hazard ratio [HR] 1.16, 95% simulation interval [SI] 0.78-1.74). Compared with cancer-free women, cancer survivors had similar probabilities of pursuing any treatment (adjusted HR [aHR] 0.88, 95% SI 0.46-1.56), using hormones or medications (aHR 0.86, 95% SI 0.46-1.63), or undergoing intrauterine insemination (aHR 1.26, 95% SI 0.40-5.88) to conceive. Cancer survivors were slightly more likely to pursue surgical interventions to become pregnant (HR 1.55, 95% SI 0.67-3.71). Of those who visited a doctor but declined to pursue fertility treatment, one-quarter of women reported declining treatment due to cost. CONCLUSION: Cancer survivors did not use fertility treatments at higher rates than the general population. Further counseling and education surrounding fertility options are recommended for young adult female cancer patients after treatment is completed.

DNA methylation as a window into female reproductive aging.

People with ovaries experience reproductive aging as their reproductive function and system declines. This has significant implications for both fertility and long-term health, with people experiencing an increased risk of cardiometabolic disorders after menopause. Reproductive aging can be assessed through markers of ovarian reserve, response to fertility treatment or molecular biomarkers, including DNA methylation. Changes in DNA methylation with age associate with poorer reproductive outcomes, and epigenome-wide studies can provide insight into genes and pathways involved. DNA methylation-based epigenetic clocks can quantify biological age in reproductive tissues and systemically. This review provides an overview of hallmarks and theories of aging in the context of the reproductive system, and then focuses on studies of DNA methylation in reproductive tissues.

People with ovaries experience a natural decline in the function of their reproductive system as they age. This decline eventually leads to menopause, and after menopause, people have an increased risk of developing cardiovascular or other chronic diseases. In the clinic, it is hard to measure aging of the reproductive system, so other markers of the ovary's function, like the number of remaining eggs, are used. We can also measure reproductive aging using molecular biomarkers, which can help us determine when a person's molecular age is different from their chronological age. This review focuses on an overview of biological processes and theories associated with aging, and then focuses on what can be learned from molecular biomarkers.

Examining decisional needs and contextual factors influencing fertility status assessment among young female survivors of childhood cancer: A sequential mixed methods study protocol.

INTRODUCTION: Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health needs of emerging adult female survivors of childhood cancer and to identify decisional and contextual factors that influence pursuit of FSA using an explanatory sequential quantitative to qualitative mixed methods design. METHODS AND ANALYSIS: This study will enroll 325 female survivors (aged 18 to 29 years and >1-year post treatment; diagnosed with cancer < age 21 years) from four cancer centers in the United States. Sociodemographic and developmental factors, reproductive knowledge and values, decisional needs, and receipt of an FSA will be assessed through a web-based survey. Informed by survey findings, a subset of participants will be recruited for qualitative interviews to explore decisional factors associated with uptake of an FSA. Clinical data will be abstracted from the medical records. Multivariable logistic regression models will be developed to identify factors associated with FSA and qualitative descriptive analysis will be used to develop themes from the interviews. Quantitative and qualitative findings will be merged using a joint display to develop integrated study conclusions and direct future interventional research.

The Risk of Infertility After Surgery for Benign Ovarian Cysts.

Background: There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. However, it is unclear whether ovarian cyst surgery puts women at risk of future infertility. This study investigates whether surgery for benign ovarian cysts is associated with long-term infertility risk. Methods: Women aged 22-45 years (n = 1,537) were invited to participate in an interview about their reproductive histories, including whether they ever had infertility or ovarian cyst surgery. Each woman reporting cyst surgery was randomly matched to a comparison woman, who was assigned an artificial surgery age equal to that of her match. Matching was repeated 1,000 times. Adjusted Cox models were fit to examine time to infertility after surgery for each match. A subset of women was invited to participate in a clinic visit to assess markers of ovarian reserve (anti-Müllerian hormone [AMH], antral follicle count). Results: Approximately 6.1% of women reported cyst surgery. Infertility after surgery was more common for women reporting cyst surgery than those without surgery after adjusting for age, race, body mass index, cancer history, parity before assigned surgery age, history of infertility before surgery age, and endometriosis (median-adjusted hazard ratio 2.41, 95% simulation interval 1.03-6.78). The estimated geometric mean (95% confidence interval [CI]) AMH levels of those who reported a history of ovarian cyst surgery were 1.08 (95% CI: 0.57-2.05) times those of women who reported no history of surgery. Conclusions: Those with a history of ovarian cyst surgery were more likely to report having a history of infertility compared with age-matched women who reported no history of cyst surgery. It is possible that both ovarian surgery to remove cysts and the conditions that lead women to develop cysts requiring surgery may affect subsequent successful conception.

Racial and ethnic disparities in assisted reproductive technology: a systematic review.

There is emergent scientific literature examining the disparities in reproductive care of women in the United States. Reproduction is a basic human right and there are unique challenges that racial and ethnic minorities face in accessing fertility care and assisted reproductive technology. The identification of these disparities can aid in identifying areas for interventions to improve and resolve, the inequities that exist in providing care for minority populations. A literature search was performed using PubMed to identify articles with data specific to racial and ethnic differences in study populations as it related to infertility, access to care, and treatment outcomes. The following review and collection of articles provide a comprehensive overview of the disparities that exist, the factors that contribute to these disparities, and recommendations for how providers and health care systems may begin to resolve the gaps in equitable care.

Correction: Standen et al. Aboriginal Population and Climate Change in Australia: Implications for Health and Adaptation Planning. Int. J. Environ. Res. Public Health 2022, 19, 7502

In the original publication [...].

Aboriginal Population and Climate Change in Australia: Implications for Health and Adaptation Planning.

The health impacts of climate are widely recognised, and extensive modelling is available on predicted changes to climate globally. The impact of these changes may affect populations differently depending on a range of factors, including geography, socioeconomics and culture. This study reviewed current evidence on the health risks of climate change for Australian Aboriginal populations and linked Aboriginal demographic data to historical and projected climate data to describe the distribution of climate-related exposures in Aboriginal compared to non-Aboriginal populations in New South Wales (NSW), Australia. The study showed Aboriginal populations were disproportionately exposed to a range of climate extremes in heat, rainfall and drought, and this disproportionate exposure was predicted to increase with climate change over the coming decades. Aboriginal people currently experience higher rates of climate-sensitive health conditions and socioeconomic disadvantages, which will impact their capacity to adapt to climate change. Climate change may also adversely affect cultural practices. These factors will likely impact the health and well-being of Aboriginal people in NSW and inhibit measures to close the gap in health between Aboriginal and non-Aboriginal populations. Climate change, health and equity need to be key considerations in all policies at all levels of government. Effective Aboriginal community engagement is urgently needed to develop and implement climate adaptation responses to improve health and social service preparedness and secure environmental health infrastructure such as drinking water supplies and suitably managed social housing. Further Aboriginal-led research is required to identify the cultural impacts of climate change on health, including adaptive responses based on Aboriginal knowledges.

There and back again; historical perspective and future directions for Vaccinium breeding and research studies.

The genus Vaccinium L. (Ericaceae) contains a wide diversity of culturally and economically important berry crop species. Consumer demand and scientific research in blueberry (Vaccinium spp.) and cranberry (Vaccinium macrocarpon) have increased worldwide over the crops' relatively short domestication history (~100 years). Other species, including bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), and ohelo berry (Vaccinium reticulatum) are largely still harvested from the wild but with crop improvement efforts underway. Here, we present a review article on these Vaccinium berry crops on topics that span taxonomy to genetics and genomics to breeding. We highlight the accomplishments made thus far for each of these crops, along their journey from the wild, and propose research areas and questions that will require investments by the community over the coming decades to guide future crop improvement efforts. New tools and resources are needed to underpin the development of superior cultivars that are not only more resilient to various environmental stresses and higher yielding, but also produce fruit that continue to meet a variety of consumer preferences, including fruit quality and health related traits.

Factors Associated with Unplanned Pregnancy Among Cancer Survivors.

Background: Approximately half of all pregnancies in the United States are unintended. However, women who are diagnosed with cancer in their reproductive years may be a unique population. This study examines the prevalence of and identifies factors associated with unplanned pregnancy among cancer survivors. Materials and Methods: Female cancer survivors aged 22-45 years, diagnosed between ages 20-35 years and at least 2 years postdiagnosis, and women with no history of cancer were interviewed about their reproductive histories, including pregnancy intention. Using a random matching process, comparison women were assigned an artificial age at cancer diagnosis equal to that of her cancer survivor match. An adjusted Cox model was fit examining time to unintended pregnancy after cancer for each of 1,000 matches. Cox proportional hazards models were also fit to assess associations between participant characteristics and unplanned pregnancy after cancer among survivors. Results: Cancer survivors (n = 1,282) and comparison women (n = 1,073) reported a similar likelihood of having an unplanned pregnancy in models adjusted for race, income, history of sexually-transmitted infection, and history of unplanned pregnancy before diagnosis (adjusted hazard ratio [aHR] 1.06, 95% simulation interval 0.85-1.36). After adjusting for confounders, unplanned pregnancy among survivors was associated with age <30 years at diagnosis (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.32-2.44), black race (HR: 1.55, 95% CI: 1.13-2.12; referent: white), receiving fertility counseling (aHR: 1.41, 95% CI: 1.04-1.92), and having at least one child before diagnosis (aHR: 1.44, 95% CI: 1.05-1.97). Conclusion: Cancer survivors and comparison women had similar likelihood of unplanned pregnancy. Rates of unplanned pregnancy after cancer were not higher for cancer survivors compared with comparison women, but 46.4% of survivors with a postcancer pregnancy reported an unplanned pregnancy. Cancer patients may benefit from patient-centered guidelines and counseling before cancer treatment that covers both risks of infertility and risks of unplanned pregnancy.

Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders.

Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk-benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70-80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.

Pediatric BMI changes during COVID-19 pandemic: An electronic health record-based retrospective cohort study.

BACKGROUND: Beginning March 2020, the COVID-19 pandemic has disrupted different aspects of life. The impact on children's rate of weight gain has not been analysed. METHODS: In this retrospective cohort study, we used United States (US) Electronic Health Record (EHR) data from Optum® to calculate the age- and sex- adjusted change in BMI (∆BMIadj) in individual 6-to-17-year-old children between two well child checks (WCCs). The mean of individual ∆BMIadj during 2017-2020 was calculated by month. For September-December WCCs, the mean of individual ∆BMIadj (overall and by subgroup) was reported for 2020 and 2017-2019, and the impact of 2020 vs 2017-2019 was tested by multivariable linear regression. FINDINGS: The mean [95% Confidence Interval - CI] ∆BMIadj in September-December of 2020 was 0·62 [0·59,0·64] kg/m2, compared to 0·31 [0·29, 0·32] kg/m2 in previous years. The increase was most prominent in children with pre-existing obesity (1·16 [1·07,1·24] kg/m2 in 2020 versus 0·56 [0·52,0·61] kg/m2 in previous years), Hispanic children (0·93 [0·84,1·02] kg/m2 in 2020 versus 0·41 [0·36,0·46] kg/m2 in previous years), and children who lack commercial insurance (0·88 [0·81,0·95] kg/m2 in 2020 compared to 0·43 [0·39,0·47] kg/m2 in previous years). ∆BMIadj accelerated most in ages 8-12 and least in ages 15-17. INTERPRETATION: Children's rate of unhealthy weight gain increased notably during the COVID-19 pandemic across demographic groups, and most prominently in children already vulnerable to unhealthy weight gain. This data can inform policy decisions critical to child development and health as the pandemic continues to unfold. FUNDING: Amgen, Inc.

Assessment of a novel genetic counselling intervention to inform assisted reproductive technology treatments and other family-building options in adults with cystic fibrosis.

Many patients with cystic fibrosis (CF) are living well into their adult years and contemplating parenthood. Previous studies have shown that there is an opportunity to improve understanding of inheritance and genetics among individuals with CF. This study explored whether a genetic counselling intervention would be associated with a change in knowledge and/or beliefs about genetics and family-building options. Adults (age ≥ 18 years) presenting to a CF clinic were approached for inclusion. Participants completed a pre-intervention survey to measure their knowledge of CF genetics, as well as perceptions and understanding of assisted reproductive technology treatments and other family-building options. Subjects then partook in a genetic counselling session. Subjects repeated the survey immediately after the session and 1-3 months later. Data analysis used one-way analysis of variance (ANOVA), repeated measures ANOVA and multiple linear regression. Thirty-five subjects [19 (54%) men and 16 (45%) women] with a mean (±standard deviation) age of 28 ±â€¯5.64 years were enrolled in the study. Before the intervention, 61.69% ± 4.50 of knowledge-based questions were answered correctly. Immediately after the intervention, the mean score increased to 77.71% ± 3.23, but this decreased to 69.48% ± 4.02 for the third test (P < 0.05, repeated measures ANOVA). Six individuals changed their family-building preference following the genetic counselling session. A short genetic consultation was associated with a significant improvement in CF-specific genetic knowledge. However, knowledge was not retained fully for a longer time period following the consultation. Multiple discussions regarding fertility options are needed to reinforce the key concepts related to CF genetics and fertility.

The effects of oocyte donor and recipient body mass index on live birth rates and pregnancy outcomes following assisted reproduction.

OBJECTIVE: To investigate the effects of oocyte donor and recipient body mass index (BMI) on outcomes of vitrified donor oocyte assisted reproductive technology (ART). DESIGN: Retrospective cohort study. SETTING: Private fertility center. PATIENTS: A total of 338 oocyte donors and 932 recipients who underwent 1,651 embryo transfer cycles in 2008-2015. INTERVENTIONS: Multivariable log binomial regression models with cluster-weighted generalized estimating equations were used to estimate the adjusted risk ratios. MAIN OUTCOME MEASURES: Live birth, defined as the delivery of at least one live-born infant, including all embryo transfer cycles. Secondary outcomes included birth weight and gestational length only among singleton live births. RESULTS: The mean ± SD body mass indexes (BMIs) of donors and recipients were 22.6 ± 2.5 kg/m2 and 24.6 ± 4.8 kg/m2, respectively. There were no significant associations between donor BMI and probability of live birth. Recipients with BMI ≥35 kg/m2 had a significantly higher probability of live birth compared with normal-weight recipients. Among singleton live births, recipients with BMI <18.5 kg/m2 had a lower risk whereas women with BMI ≥35 kg/m2 had a higher risk of delivery in an earlier gestational week compared with normal weight women. Recipients with a BMI ≥35 kg/m2 also had a higher risk of having a low birth weight infant compared with normal-weight women. CONCLUSIONS: In the setting of vitrified donor oocyte ART, recipient BMI was positively associated with probability of live birth but negatively associated with gestational length and birth weight among singleton births.

Identifying susceptibility genes for primary ovarian insufficiency on the high-risk genetic background of a fragile X premutation.

OBJECTIVE: To identify modifying genes that explains the risk of fragile X-associated primary ovarian insufficiency (FXPOI). DESIGN: Gene-based, case/control association study, followed by a functional screen of highly ranked genes using a Drosophila model. SETTING: Participants were recruited from academic and clinical settings. PATIENT(S): Women with a premutation (PM) who experienced FXPOI at the age of 35 years or younger (n = 63) and women with a PM who experienced menopause at the age of 50 years or older (n = 51) provided clinical information and a deoxyribonucleic acid sample for whole genome sequencing. The functional screen was on the basis of Drosophila TRiP lines. INTERVENTION(S): Clinical information and a DNA sample were collected for whole genome sequencing. MAIN OUTCOME MEASURES: A polygenic risk score derived from common variants associated with natural age at menopause was calculated and associated with the risk of FXPOI. Genes associated with the risk of FXPOI were identified on the basis of the P-value from gene-based association test and an altered level of fecundity when knocked down in the Drosophila PM model. RESULTS: The polygenic risk score on the basis of common variants associated with natural age at menopause explained approximately 8% of the variance in the risk of FXPOI. Further, SUMO1 and KRR1 were identified as possible modifying genes associated with the risk of FXPOI on the basis of an untargeted gene analysis of rare variants. CONCLUSIONS: In addition to the large genetic effect of a PM on ovarian function, the additive effects of common variants associated with natural age at menopause and the effect of rare modifying variants appear to play a role in FXPOI risk.

When using donor oocytes, does embryo stage matter? An analysis of blastocyst versus cleavage stage embryo transfers using a cryopreserved donor oocyte bank.

PURPOSE: Oocyte donor in vitro fertilization (IVF) represents an ideal model to study the effects of embryo stage on reproductive success, as embryos come from young women with high-quality oocytes. Our study aimed to determine if embryo transfer stage affected outcomes in oocyte donor IVF, including the common scenario where only a limited number of quality embryos are available after culture. METHODS: This retrospective cohort analyzed anonymous vitrified donor oocyte cycles at a single clinic between 2008 and 2015. Overall, 983 recipients underwent 1178 warming cycles resulting in fresh transfer of one-to-two embryos. Our primary outcome was live birth; secondary outcomes included multiple birth, birthweight, and gestational age. Log binomial regression with cluster-weighted generalized estimating equations were used to calculate adjusted risk ratios (aRR) accounting for recipient age, race, and transfer year. RESULTS: Among 132 cleavage and 1046 blastocyst transfer cycles, cleavage transfers were associated with lower probability of live birth (aRR 0.72, 95% CI 0.59-0.88). Subgroup analysis focused on cycles with a limited number of quality embryos 3 days post-fertilization (≤2), as clinically these women were most likely to be considered for cleavage transfers. Among these cycles (120 cleavage, 371 blastocyst), cleavage transfers were still associated with lower live birth rates compared to blastocyst (aRR 0.66, 95% CI 0.51-0.87) CONCLUSIONS: Even in a donor oocyte model with high-quality oocytes, there was a benefit to extended culture and blastocyst transfer, including when only one-to-two quality embryos were available after early culture. This is possibly owed to improved uterine synchronicity or decreased contractility.

Ovarian stimulation for fertility preservation in women with cancer: A systematic review and meta-analysis comparing random and conventional starts.

OBJECTIVE: In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing cancer treatments. Our objective was to compare clinical outcomes among female cancer patients who underwent a conventional early follicular phase-start ovarian stimulation cycle and those who underwent a random-start ovarian stimulation cycle. EVIDENCE REVIEW: A systematic review of the literature was performed in accordance with PRISMA guidelines. Medline, Embase.com, Scopus, Cochrane Library, and Clinicaltrials.gov databases were searched to identify all original research published in English through July 2020 on the topic of female cancer patients undergoing ovarian stimulation with a random or conventional start. Studies lacking a comparison group or including women who had already undergone chemotherapy at the time of ovarian stimulation were excluded. The primary author assessed all identified article titles and abstracts, and two independent reviewers assessed full-text articles and extracted data. A meta-analysis with a random-effects model was used to calculate weighted mean differences (WMDs) for outcomes of interest. The primary outcome was the number of mature (meiosis II) oocytes retrieved. Secondary outcomes included duration of stimulation, total dose of gonadotropins, total number of oocytes retrieved, fertilization rate, and number of embryos or zygotes cryopreserved. RESULTS: A total of 446 articles were screened, and 9 full-text articles (all retrospective cohort or prospective observational) were included for review. Additionally, pooled primary retrospective data from two institutions were included. In total, data from 10 studies including 1653 women were reviewed. Five studies reported the number of embryos cryopreserved, and four reported fertilization rates. Random-start cycles were slightly longer (WMD 0.57 days, 95 % confidence interval [CI] 0.0-1.14 days) and used more total gonadotropins (WMD 248.8 international units, 95 % CI 57.24-440.40) than conventional-start cycles. However, there were no differences in number of mature oocytes retrieved (WMD 0.41 oocytes, 95 % CI -0.84-1.66), number of total oocytes retrieved (WMD 0.90 oocytes, 95 % CI -0.21-2.02), fertilization rates (WMD -0.12, 95 % CI -1.22-0.98), or number of embryos cryopreserved (WMD 0.12 embryos, 95 %CI -0.98-1.22) between random-start and conventional-start cycles. All outcomes except for the parameter "total oocytes retrieved" yielded an I2 of over 50 %, indicating substantial heterogeneity between studies. CONCLUSION(S): Although random-start cycles may entail a longer duration of stimulation and use more total gonadotropins than conventional-start cycles, the absolute differences are small and likely do not significantly affect treatment costs. The similar numbers of mature oocytes retrieved, fertilization rates, and number of embryos cryopreserved in the two start-types suggest that they do not differ in any clinically important ways. Given that random-start cycles can be initiated quickly, they may help facilitate fertility preservation for cancer patients.