Adoption as an Alternative Family-Building Strategy: Perceptions of Female, Young Adult Cancer Survivors Receiving Gonadotoxic Treatments.

Female survivors of young adult (YA) cancers are at risk of fertility impacts following cancer treatment. For these women, fertility-related distress is both prevalent and persistent. Yet there is little research regarding survivors' perspectives on alternative family-building options, particularly adoption. This exploratory secondary data analysis analyzed semistructured interviews and explored survivors' views of adoption. Overall, female YA survivors reported openness to adoption as a possible substitute for biological conception and an alternative to fertility preservation. It is imperative that this population receives support in decision-making around and consideration of the unique barriers to adoption for cancer survivors.

Impact of Financial Costs on Patients' Fertility Preservation Decisions: An Examination of Qualitative Data from Female Young Adults with Cancer and Oncology Providers.

Purpose: To examine the impact of financial costs on fertility preservation decisions among female young adults (YAs) with cancer. Methods: Female YAs (N = 18; aged 21-36) with a history of cancer and oncology providers (N = 12) were recruited from an National Cancer Institute-designated comprehensive cancer center in a state without insurance coverage for fertility preservation. YAs and providers completed individual interviews and a brief online assessment. Qualitative description using thematic analysis was used to identify, analyze, and report common themes. Descriptive statistics was used to characterize the sample. Results: Female YAs and oncology providers highlighted the critical role that high out-of-pocket costs play in YAs' fertility preservation decisions along with the value that enhanced insurance coverage for fertility preservation would have for increasing female YAs' access to and utilization of fertility preservation. Although providers were concerned about preservation costs for their patients, they reported that their concerns did not impact whether they referred interested female YAs to reproductive specialists. Oncology providers expressed concern about inequities in utilization of fertility preservation for female and racially/ethnically minoritized YAs that were exacerbated by the high out-of-pocket fertility preservation costs. Conclusion: Cost is a significant barrier to fertility preservation for female YA cancer patients. Female YAs of reproductive age may benefit from decision support tools to assist with balancing the cost of fertility preservation with their values and family building goals. Policy-relevant interventions may mitigate cost barriers and improve access to care.

The #IVF journey: content analysis of IVF videos on TikTok.

RESEARCH QUESTION: What patient populations and outcomes are depicted on IVF videos on the short-form video-sharing application 'TikTok'? DESIGN: This cross-sectional study investigated the 100 most-viewed videos utilizing the #IVF hashtag on TikTok. Only videos in English or Spanish were included in the analysis. An automated web-scraping platform was used to extract information from these videos. Standardized video coding was used to evaluate the featured subject(s), phase of care and IVF outcomes from the videos. RESULTS: Videos meeting the inclusion criteria (n=93) had 731 million views, 91 million likes and 893,000 shares. Patients' personal stories about IVF are over-represented relative to videos created by healthcare professionals. #IVF videos popular on TikTok disproportionately depict same-sex couples (38.1%), gestational carriers (14.0%), multiple gestations (60.0%) and live births (89.3%) relative to real-world data. Among the videos making scientific claims (n=16), nearly all were moderately to highly accurate (93.8%). Most videos had a positive (55.9%) or neutral (5.5%) tone towards IVF. CONCLUSIONS: Popular #IVF videos on TikTok contribute to public discourse about infertility, and highlight demographics that have traditionally been under-represented in health care. Videos rarely focused on health education or made informational claims, with low scores on measures of quality of information and actionability. This gap represents an opportunity for health providers and educators to create more engaging and educational content to reach patients considering IVF.

Oncofertility research pitfall? Recall bias in young adult cancer survivors.

Objective: To assess recall bias by evaluating how well female cancer survivors remember details regarding their cancer diagnosis, treatment, and fertility preservation (FP) counseling.Oncofertility literature cites recall bias as a pitfall of retrospective surveys, but limited data exist to quantify this bias. Design: Retrospective secondary analysis of cross-sectional survey data. Setting: Single academic medical center. Patients: Female oncology patients of reproductive age, 18-44 years old, at least 6 months past their last chemotherapy treatment. Interventions: Not applicable. Main Outcome Measures: Recall of details surrounding cancer diagnosis and chemotherapy regimens, recall of FP counseling and ovarian reserve testing, and rates of chart-documented FP counseling. Results: In total, 117 patients completed the survey, with 112 verified via chart review. When asked to report the chemotherapy regimen, 57% (64 of the 112) marked "I don't know/prefer not to say." Regarding FP, 80% (90 of the 112) denied being offered counseling. Of the 37 (33%) who had documented FP conversations, 13 (35%) did not recall mention of fertility. Only 2 of 8 patients with ovarian reserve testing recalled this being performed at their initial visit. Multivariable logistic regression revealed older age was significantly associated with not being offered FP (odds ratio [OR] 0.87). Conclusions: Our results confirm that the accuracy of oncology patients' reporting is limited by a poor recall, particularly regarding their specific chemotherapy regimen. More than 1 in 3 patients documented to have been offered FP counseling do not recall this discussion. Importantly, only one-third of cancer survivors had chart-documented FP counseling. Increased efforts are needed to ensure adequate follow-up beyond the initial visit.

Body mass index is negatively associated with a good perinatal outcome after in vitro fertilization among patients with polycystic ovary syndrome: a national study.

Objective: To evaluate the association between body mass index (BMI) and good perinatal outcomes after in vitro fertilization (IVF) among women with polycystic ovary syndrome (PCOS). Design: Retrospective cohort study using 2012-2015 Society for Assisted Reproductive Technology Clinic Outcomes Reporting System data. Setting: Fertility clinics. Patients: To identify patients most likely to have PCOS, we included women with a diagnosis of ovulation disorder and serum antimüllerian hormone >4.45 ng/mL. Exclusion criteria included age ≥ 41 years, secondary diagnosis of diminished ovarian reserve, preimplantation genetic testing, and missing BMI or primary outcome data. Interventions: None. Main Outcome Measures: Good perinatal outcome, defined as a singleton live birth at ≥ 37 weeks with birth weight ≥ 2,500 g and ≤ 4,000 g. Results: The analysis included 9,521 fresh, autologous IVF cycles from 8,351 women. Among women with PCOS, the proportion of cycles with a good perinatal outcome was inversely associated with BMI: underweight 25.1%, normal weight 22.7%, overweight 18.9%, class I 18.4%, class II 14.9%, and class III or super obesity 12.2%. After adjusting for confounders, women in the highest BMI category had 51% reduced odds of a good perinatal outcome compared with normal weight women (adjusted odds ratio 0.49, 95% confidence interval 0.36-0.67). Conclusions: Among women with PCOS undergoing fresh, autologous IVF, the odds of a good perinatal outcome decline with increasing BMI. Women with PCOS should be counseled that the odds of achieving a good perinatal outcome decrease as their weight increases.

Impact of increasing antimüllerian hormone level on in vitro fertilization fresh transfer and live birth rate.

Objective: The objective of our study was to assess the association between AMH and live birth among women with elevated AMH undergoing first fresh IVF. Serum antimüllerian hormone (AMH) correlates with oocyte yield during in vitro fertilization (IVF). However, there are limited data regarding IVF outcomes in women with elevated AMH levels. Design: Retrospective cohort study using the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System database from 2012-2014. Setting: Fertility clinics reporting to Society for Assisted Reproductive Technology. Patients: First, fresh, autologous IVF cycles with elevated AMH levels (≥5.0 ng/mL). Subanalyses were performed to examine patients with or without polycystic ovary syndrome (PCOS). Interventions: None. Main Outcome Measures: Odds of live birth. Results: Our cohort included 10,615 patients with elevated an AMH level, including 2,707 patients with PCOS only. The adjusted odds of live birth per initiated cycle were significantly lower per each unit increase in the AMH level (odds ratio, 0.97; 95% confidence interval, 0.96-0.98). Increasing AMH level was associated with increased cancellation of fresh transfer (odds ratio, 1.12; 95% confidence interval, 1.10-1.15) up to an AMH level of 12 ng/mL. The decrease in the live birth rate appears to be caused by the increasing incidence of cancellation of fresh transfer because the live birth rate per completed transfer was maintained. Similar trends were observed in the PCOS and non-PCOS subanalyses. Conclusions: Among patients with AMH levels of ≥5 ng/mL undergoing fresh, autologous IVF, each unit increase in AMH level is associated with a 3% decrease in odds of live birth because of the increased incidence of fresh embryo transfer cancellation.

Can high antimüllerian hormone mitigate some of the age-related decline in live birth rates? The association between antimüllerian hormone and live birth among women over 40 undergoing in vitro fertilization.

OBJECTIVE: To examine the association between serum antimüllerian hormone (AMH) and live birth among women aged ≥41 years undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study using the 2012-2014 Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. SETTING: Fertility clinics reporting to the Society for Assisted Reproductive Technology. PATIENTS: The analysis included 7,819 patients aged ≥41 years who underwent a first fresh, autologous IVF cycle during the study period. Cycles with preimplantation genetic testing were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Live birth rate. RESULTS: The empirical distribution of AMH was examined, and extreme values were observed. Therefore, the natural logarithm transformation of AMH (log-AMH) was used in all analyses. Before adjustment for covariates, a one-unit increase in log-AMH was associated with doubling of the odds of live birth up to a log-AMH of -0.34 (equivalently, AMH, 0.71 ng/mL; odds ratio [OR], 2.02; 95% confidence interval [CI], 1.66-2.46). Above an AMH level of 0.71 ng/mL, the odds of live birth increased by only 40% with each unit increase in log-AMH (OR, 1.40; 95% CI, 1.22-1.61). After adjusting for covariates, the odds of live birth increased by 91% with each unit increase in log-AMH up to -0.34 (AMH, 0.71 ng/mL; OR, 1.91; 95% CI, 1.56-2.34). Above an AMH level of 0.71 ng/mL, the odds of live birth increased by only 32% with each unit increase in log-AMH (OR, 1.32; 95% CI, 1.15-1.53). CONCLUSIONS: Among women aged ≥41 years undergoing fresh, autologous IVF, the odds of live birth significantly increase with increasing serum AMH level. As the AMH level increases above 0.71 ng/mL, the association maintains statistical significance, but the effect size is diminished.

Addressing Barriers to Fertility Preservation for Cancer Patients: The Role of Oncofertility Patient Navigation.

BACKGROUND: Infertility is a common late effect for cancer survivors. Whereas assisted reproductive technology has made it possible for survivors to take steps to preserve fertility before starting treatment, only a minority of patients proceed with preservation. Patient-, provider-, health system-, and societal-level barriers to fertility preservation (FP) exist. Oncofertility patient navigation is a valuable resource for addressing FP barriers. OBJECTIVES: To highlight the critical role of oncofertility patient navigation in addressing barriers to FP within an academic oncofertility program. METHODS: The role of the oncofertility patient navigator in reducing FP barriers, promoting informed decision-making, and ensuring program sustainability is described. Program metrics illustrating the impact of oncofertility patient navigation on referrals for FP counseling and access to FP in the last year also are provided. DISCUSSION: The oncofertility program at our academic adult and pediatric medical centers aims to facilitate rapid referral to fertility counseling and preservation services for postpubertal cancer patients. The patient navigator is integral to the success of the program. The navigator ensures that patients are: (1) well-informed about the potential impact of cancer on fertility and FP options, (2) aware of available resources (eg, financial) for pursuing FP, (3) able to access FP services if desired, and (4) well supported in making an informed FP decision. The inclusion of the patient navigator has led to an almost 2-fold increase in referrals for FP counseling in the past year over the historic annual average. CONCLUSIONS: Our institution's oncofertility program, with patient navigation at the core, provides a potential model for increasing patient access to oncofertility care and promoting program sustainability. Oncofertility patient navigation is a valuable resource for providing patients and families with education and support regarding FP decision-making, as well as addressing the multilevel barriers to FP.

Development of a fertility risk calculator to predict individualized chance of ovarian failure after chemotherapy.

PURPOSE: To develop an innovative machine learning (ML) model that predicts personalized risk of primary ovarian insufficiency (POI) after chemotherapy for reproductive-aged women. Currently, individualized prediction of a patient's risk of POI is challenging. METHODS: Authors of published studies examining POI after gonadotoxic therapy were contacted, and six authors shared their de-identified data (N = 435). A composite outcome for POI was determined for each patient and validated by 3 authors. The primary dataset was partitioned into training and test sets; random forest binary classifiers were trained, and mean prediction scores were computed. Institutional data collected from a cross-sectional survey of cancer survivors (N = 117) was used as another independent validation set. RESULTS: Our model predicted individualized risk of POI with an accuracy of 88% (area under the ROC 0.87, 95% CI: 0.77-0.96; p < 0.001). Mean prediction scores for patients who developed POI and who did not were 0.60 and 0.38 (t-test p < 0.001), respectively. Highly weighted variables included age, chemotherapy dose, prior treatment, smoking, and baseline diminished ovarian reserve. CONCLUSION: We developed an ML-based model to estimate personalized risk of POI after chemotherapy. Our web-based calculator will be a user-friendly decision aid for individualizing risk prediction in oncofertility consultations.

Oocyte cryopreservation versus ovarian tissue cryopreservation for adult female oncofertility patients: a cost-effectiveness study.

PURPOSE: In December 2019, the American Society for Reproductive Medicine designated ovarian tissue cryopreservation (OTC) as no longer experimental and an alternative to oocyte cryopreservation (OC) for women receiving gonadotoxic therapy. Anticipating increased use of OTC, we compare the cost-effectiveness of OC versus OTC for fertility preservation in oncofertility patients. METHODS: A cost-effectiveness model to compare OC versus OTC was built from a payer perspective. Costs and probabilities were derived from the literature. The primary outcome for effectiveness was the percentage of patients who achieved live birth. Strategies were compared using incremental cost-effectiveness ratios (ICER). All inputs were varied widely in sensitivity analyses. RESULTS: In the base case, the estimated cost for OC was $16,588 and for OTC $10,032, with 1.56% achieving live birth after OC, and 1.0% after OTC. OC was more costly but more effective than OTC, with an ICER of $1,163,954 per live birth. In sensitivity analyses, OC was less expensive than OTC if utilization was greater than 63%, cost of OC prior to chemotherapy was less than $8100, cost of laparoscopy was greater than $13,700, or standardized discounted costs were used. CONCLUSIONS: With current published prices and utilization, OC is more costly but more effective than OTC. OC becomes cost-saving with increased utilization, when cost of OC prior to chemotherapy is markedly low, cost of laparoscopy is high, or standardized discounted oncofertility pricing is assumed. We identify the critical thresholds of OC and OTC that should be met to deliver more cost-effective care for oncofertility patients.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin.

Men consume the most nicotine and cannabis products but impacts on sperm epigenetics are poorly characterized. Evidence suggests that preconception exposure to these drugs alters offspring neurodevelopment. Epigenetics may in part facilitate heritability. We therefore compared effects of exposure to tetrahydrocannabinol (THC) and nicotine on DNA methylation in rat sperm at genes involved in neurodevelopment. Reduced representation bisulfite sequencing data from sperm of rats exposed to THC via oral gavage showed that seven neurodevelopmentally active genes were significantly differentially methylated versus controls. Pyrosequencing data revealed majority overlap in differential methylation in sperm from rats exposed to THC via injection as well as those exposed to nicotine. Neurodevelopmental genes including autism candidates are vulnerable to environmental exposures and common features may mediate this vulnerability. We discovered that autism candidate genes are significantly enriched for bivalent chromatin structure, suggesting this configuration may increase vulnerability of genes in sperm to disrupted methylation.

Epigenetic alterations in cytochrome P450 oxidoreductase (Por) in sperm of rats exposed to tetrahydrocannabinol (THC).

As marijuana legalization is increasing, research regarding possible long-term risks for users and their offspring is needed. Little data exists on effects of paternal tetrahydrocannabinol (THC) exposure prior to reproduction. This study determined if chronic THC exposure alters sperm DNA methylation (DNAm) and if such effects are intergenerationally transmitted. Adult male rats underwent oral gavage with THC or vehicle control. Differentially methylated (DM) loci in motile sperm were identified using reduced representation bisulfite sequencing (RRBS). Another cohort was injected with vehicle or THC, and sperm DNAm was analyzed. Finally, THC-exposed and control adult male rats were mated with THC-naïve females. DNAm levels of target genes in brain tissues of the offspring were determined by pyrosequencing. RRBS identified 2,940 DM CpGs mapping to 627 genes. Significant hypermethylation was confirmed (p < 0.05) following oral THC administration for cytochrome P450 oxidoreductase (Por), involved in toxin processing and disorders of sexual development. Por hypermethylation was not observed after THC injection or in the subsequent generation. These results support that THC alters DNAm in sperm and that route of exposure can have differential effects. Although we did not observe evidence of intergenerational transmission of the DNAm change, larger studies are required to definitively exclude this possibility.

Preconception Evaluation Before In Vitro Fertilization.

IMPORTANCE: Infertility poses a substantial public health problem for women of reproductive age, in the United States and globally. Infertility can be overcome with a variety of emerging assisted reproductive technologies (ARTs). In vitro fertilization (IVF) currently represents the most commonly utilized method of ART and is typically associated with the highest clinical pregnancy rate and live birth rate compared with other infertility treatment options. However, proper preconception evaluation and counseling is paramount for optimizing IVF and pregnancy outcomes. OBJECTIVE: This article aims to outline current guidelines and recommendations for comprehensive preconception evaluation before initiation of IVF. EVIDENCE ACQUISITION: Articles were obtained from PubMed, ACOG committee opinions 781 and 762, and relevant textbook chapters. RESULTS: A variety of recommendations and best practices exist for optimally managing patients seeking IVF. Special attention must be paid to the workup of certain patient populations, such as those with age older than 35 years, uterine abnormalities, comorbidities (especially hypertension, diabetes, and thrombophilias), and obesity. In addition, many lifestyle factors must be addressed before IVF initiation, such as smoking, illicit drug use, and inadequate nutrition. Preconception counseling and expectation management is key to optimizing pregnancy outcome. CONCLUSION AND RELEVANCE: A myriad of patient and environmental factors impact the potential success rates of IVF in treating infertility. Providers must be equipped to provide data-driven, patient-centered counseling before initiation of IVF.

Total follicle stimulating hormone dose is negatively correlated with live births in a donor/recipient model with fresh transfer: an analysis of 8,627 cycles from the Society for Assisted Reproductive Technology Registry.

OBJECTIVE: Oocyte donation has optimized our understanding of ovarian stimulation. Increasing the follicle-stimulating hormone (FSH) dose has been shown to adversely affect live birth rates in autologous cycles. Our objective is to assess whether this relationship holds true within the donor/recipient population. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENTS: Data from 2014-2016 included 8,627 fresh donor cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Live birth, clinical pregnancy, and miscarriage rates. RESULTS: The mean donor age ± standard deviation (SD) was 25.8 ± 2.8 years. Donors underwent a median of 16 days (interquartile range [IQR] 12, 19) of stimulation with a median (IQR) total FSH dose and daily dose of 2,350.0 (1,800.0, 3,025.0) and 153.8 (113.2, 205.0) IU, respectively. The live birth rate was 56.7% per transfer. For every 500-unit increase in FSH dose, there was a 3% reduction in the odds of a live birth (odds ratio [OR] 0.97; 95% confidence interval 0.95, 0.99), and a 3% reduction in the odds of a clinical pregnancy (OR 0.97; 95% confidence interval 0.95, 0.99). Days of stimulation and average daily dose were not significantly associated with live birth or clinical pregnancy. No significant association was found between miscarriage rates and total FSH dose, days of stimulation, or average daily dose. CONCLUSION: This is a novel report of a negative association of total FSH dosage on fresh IVF live births, performed in the donor population to control for oocyte source and endometrial receptivity.

Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.

Parental cannabis use has been associated with adverse neurodevelopmental outcomes in offspring, but how such phenotypes are transmitted is largely unknown. Using reduced representation bisulphite sequencing (RRBS), we recently demonstrated that cannabis use is associated with widespread DNA methylation changes in human and rat sperm. Discs-Large Associated Protein 2 (DLGAP2), involved in synapse organization, neuronal signaling, and strongly implicated in autism, exhibited significant hypomethylation (p < 0.05) at 17 CpG sites in human sperm. We successfully validated the differential methylation present in DLGAP2 for nine CpG sites located in intron seven (p < 0.05) using quantitative bisulphite pyrosequencing. Intron 7 DNA methylation and DLGAP2 expression in human conceptal brain tissue were inversely correlated (p < 0.01). Adult male rats exposed to delta-9-tetrahydrocannabinol (THC) showed differential DNA methylation at Dlgap2 in sperm (p < 0.03), as did the nucleus accumbens of rats whose fathers were exposed to THC prior to conception (p < 0.05). Altogether, these results warrant further investigation into the effects of preconception cannabis use in males and the potential effects on subsequent generations.

Clinical pregnancy and live birth increase significantly with every additional blastocyst up to five and decline after that: an analysis of 16,666 first fresh single-blastocyst transfers from the Society for Assisted Reproductive Technology registry.

OBJECTIVE: To study the association between the number of blastocysts available and pregnancy outcomes in first fresh autologous single blastocyst transfer cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Patients from the Society for Assisted Reproductive Technology reporting fertility clinics (n=16,666). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of blastocysts and each outcome. RESULT(S): When comparing fresh single blastocyst transfer rates, the odds of a positive pregnancy outcome (CP) increased significantly with each additional supernumerary blastocyst up to five and declined by 2% for every additional blastocyst after five. Similarly, the odds of an LB was 17% higher for each additional blastocyst up to five and declined by 2% for every additional blastocyst after five. There was no significant association between blastocyst number and miscarriage rate. CONCLUSION(S): Odds of positive pregnancy outcomes (CP, LB) increased significantly with every additional blastocyst up to five, but declined after that, in first fresh autologous cycles with single-blastocyst transfer. The decline after five may be explained by a detrimental effect on endometrial receptivity in patients with a large number of oocytes or inadequate selection of the best embryo for transfer based on morphology alone.

Clinical pregnancy (CP) and live birth (LB) increase significantly with each additional fertilized oocyte up to nine, and CP and LB decline after that: an analysis of 15,803 first fresh in vitro fertilization cycles from the Society for Assisted Reproductive Technology registry.

OBJECTIVE: To study the association between the total number of fertilized oocytes available and pregnancy outcomes in first fresh IVF cycles with a single blastocyst transfer. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 15,803 patients from SART reporting fertility clinics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of fertilized eggs and each outcome. RESULT(S): The median number of total oocytes was 15, and the median number of fertilized oocytes was nine. The odds of a clinical pregnancy were 8% higher for each additional fertilized oocyte up to nine (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.07-1.10) and declined by 9% for every additional fertilized oocyte after nine (OR 0.91; 95% CI 0.89-0.94). Similarly, the odds of an LB was 8% higher for every additional fertilized oocyte up to none (OR 1.08; 95% CI 1.06-1.10) and declined by 8% for every additional fertilized oocyte over nine (OR 0.92; 95% CI 0.90-0.94). CONCLUSION(S): Odds of pregnancy outcomes (CP, LB) increase significantly with every additional fertilized oocyte up to nine, and CP and LB decline after that in first fresh autologous cycles with a single blastocyst transfer.

Cannabinoid exposure and altered DNA methylation in rat and human sperm.

Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched with genes having altered methylation in sperm from THC-exposed versus vehicle-exposed rats (p < 0.01). Data validity is supported by significant correlations between THC exposure levels in humans and methylation for 177 genes, and substantial overlap in THC target genes in rat sperm (this study) and genes previously reported as having altered methylation in the brain of rat offspring born to parents both exposed to THC during adolescence. In humans, cannabis use was also associated with significantly lower sperm concentration. Findings point to possible pre-conception paternal reproductive risks associated with cannabis use.