The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Natural cycle IVF reduces the risk of low birthweight infants compared with conventional stimulated IVF.

STUDY QUESTION: Are perinatal outcomes improved in singleton pregnancies resulting from fresh embryo transfers performed following unstimulated/natural cycle IVF (NCIVF) compared with stimulated IVF? SUMMARY ANSWER: Infants conceived by unstimulated/NCIVF have a lower risk of being low birthweight than infants conceived by stimulated IVF; however, this risk did not remain significant after adjusting for gestation age. WHAT IS ALREADY KNOWN: Previous studies have shown that infants born after modified NCIVF have a higher average birthweight and are less likely to be low birthweight than those infants conceived with conventional stimulated IVF. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of singleton live births in non-smoking women undergoing fresh IVF-embryo transfer cycles from 2007 to 2013 in a single IVF center. The women were stratified by stimulated (n = 174) or unstimulated (n = 190) IVF exposure status. Unstimulated/NCIVF is defined as IVF without the use of exogenous gonadotrophins, and only includes the use of HCG to time oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: Demographic data including maternal age, BMI, infertility diagnosis and IVF cycle characteristics were collected. The perinatal outcomes used for comparison between the two study groups were length of gestation, birthweight, preterm delivery, very preterm delivery, low birthweight, small for gestational age and large for gestational age. MAIN RESULTS AND ROLE OF CHANCE: Although women in the NCIVF group were older than those in the stimulated group (35.0 versus 34.2 years, P < 0.05), parity and history of prior ART cycles were comparable between the groups. The mean birthweight was significantly higher in the NCIVF group by 163 g than in the stimulated group (3436 ± 420 g versus 3273 ± 574 g, P < 0.05). Consistent with this finding, there were also less low birthweight (<2500 g) infants in the NCIVF group versus stimulated group (1 versus 8.6%, P < 0.005). The reduction in risk for low birthweight in the NCIVF group remained significant after adjustment for maternal age, infertility diagnosis, ICSI, number of embryos transferred and blastocyst transfer (odds ratio (OR) 0.07; 95% CI 0.014-0.35). As NCIVF group had less preterm infants, additional adjustment for gestational age was performed and this showed a tendency towards lower risk of low birthweight in NCIVF (OR 0.11; 95% CI 0.01-1.0). While gestational age at delivery was comparable between the groups, both preterm births (<37 weeks gestation) (31 versus 42%, P < 0.05) and very preterm births (<32 weeks gestation) (0.52 versus 6.3%, P < 0.005) were significantly reduced in the NCIVF group. However, after adjustment for potential confounders, the reduction in risk of preterm and very preterm delivery associated with the NCIVF group was no longer significant (OR 1.1; 95% CI 0.48-2.5). LIMITATIONS, REASONS FOR CAUTION: Limitations of this study are the retrospective nature of the data collection and the lack of information about parental characteristics associated with birthweight. WIDER IMPLICATIONS OF THE FINDINGS: The improved perinatal outcomes following successful unstimulated/NCIVF suggest that this treatment should be considered as a viable option for infertile couples. NCIVF could reduce potential adverse perinatal outcomes such as low birthweight related to fresh embryo transfers performed following ovarian stimulation. The etiology of the improved perinatal outcomes following NCIVF needs to be explored further to determine if the improvement is derived from endometrial factors versus follicular/oocyte factors. STUDY FUNDING/COMPETING INTERESTS: The study was supported by the following grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD K12HD047018 (W.M.), NICHD K12HD001271 (L.A.K.). The authors have no competing interests.

Quality of life in female cancer survivors: is it related to ovarian reserve?

PURPOSE: The purpose of the study is to assess the quality-of-life scores and possible association with measures of ovarian reserve in female cancer survivors compared to healthy controls of similar age. METHODS: In this prospective cohort study, fifty-nine cancer survivors aged 16-39 years and 66 healthy, similarly aged unexposed women were recruited at the University of Pennsylvania. The primary outcome measures are the generic and cancer-specific domain scores on the Quality of Life in Adult Cancer Survivors (QLACS) instrument, early follicular phase serum hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), inhibin B (INH), anti-Mullerian hormone (AMH), and ovarian ultrasound measurements [ovarian volume and antral follicle count (AFC)]. RESULTS: Cancer survivors had significantly higher total and cancer-specific domain scores compared to unexposed participants. Serum AMH, INH, ovarian volume, and AFC were lower while serum FSH was higher in cancer survivors. Although survivors exhibited diminished ovarian reserve, these markers were not independently associated with total QLACS score. Cancer survivors with irregular menstrual function were found to have lower quality-of-life (QOL) scores than those with regular cycles. CONCLUSIONS: We found that QOL appears to be significantly impaired in cancer survivors compared to controls, even when remote from initial cancer diagnosis. In addition, our study suggests that reproductive aging contributes to QOL in the setting of irregular menses and likely profound impairment of ovarian function.

Fertility preservation in the transgender patient: expanding oncofertility care beyond cancer.

While the field of oncofertility raised awareness about fertility concerns in oncology patients, new applications for fertility preservation are emerging, such as transgender medicine. As transgender medicine evolves, the number of individuals seeking gender reassignment hormone therapy is drastically increasing, generating a population of patients with unmet fertility needs and unknown reproductive potential. We present the first case report of a female-to-male (FtM) transgender patient to undergo oocyte cryopreservation before initiating androgen therapy. Our patient is a 17-year-old FtM transgender person undergoing gender transition throughout adolescence with an endocrinologist. The patient wished to complete androgen therapy before starting his first year of college to avoid gender ambiguity. After extensive consultation and psychological assessment, the patient was considered an appropriate candidate and proceeded with oocyte cryopreservation. He underwent baseline fertility testing followed by successful ovarian stimulation and surgical retrieval. We recommend that a discussion of reproductive health concerns and fertility preservation options be incorporated into the comprehensive care of transgender patients.

Fertility preservation consultation for women with cancer: are we helping patients make high-quality decisions?

To investigate the efficacy of the current fertility preservation consultation process in patients' decision-making and socio-demographic and cognitive factors that may affect patients' decision-making, a prospective pilot survey was conducted at university-based IVF centres and included women aged 18-43 years seen for fertility preservation between April 2009 and December 2010. Patients' views on consultation and decision-making about fertility preservation were measured. Among 52 women who completed the survey, more than half (52%) requested their consultation. All patients answered that consultation was a helpful resource of information, and 73% made their decision about treatment after consultation. Decisional conflict was lower in patients who felt strongly that they were given opportunities to ask questions during the consultation (P=0.001) and higher those who reported that cost was strongly influential in the treatment decision (P<0.001) and who did not receive treatment (P<0.001). Although consultation appeared to play a critical role in patients' decision-making about fertility preservation, the referral rate for consultation by oncologists is still poor. Decision-making appears to be significantly impaired in patients grappling with financial concerns and when the opportunity to ask questions is not felt to be sufficient.

What Does Dobbs v. Jackson Mean for Oncology Patients and Providers? Current Considerations for Pregnancy and Fertility in the Oncology Setting.

The incidence of cancers such as colorectal cancer, head and neck cancer, and melanoma has increased in younger patients. The number of cancer survivors is also increasing in the US. Pairing these facts together, there are many people with cancer for whom pregnancy and fertility concerns are crucial aspects of their oncologic and survivorship care. For these patients, understanding and having access to fertility preservation options is an essential part of their care. At JADPRO Live 2022, a panel of experts from diverse professions provided perspectives on the consequences for the treatment landscape after the Dobbs v. Jackson decision.

The current fertility preservation consultation model: are we adequately informing cancer patients of their options?

BACKGROUND: There is very limited information about the amount of information that cancer patients retain after a fertility preservation (FP) consultation (FPC). Our objective was to assess patients' knowledge following FPC and to examine predictors of increased knowledge. METHODS: We conducted a multi-center, cross-sectional, web-based survey at academic IVF centers, including women aged 18-43 years seen for comprehensive FPC between April 2009 and December 2010. The primary outcome measure was a knowledge score designed to assess comprehension of FP options. Analysis was performed to assess which patient variables were associated with higher knowledge scores. A 13-item knowledge tool about FP was developed (Kuder-Richardson 20=0.64). RESULT(S): Among 90 eligible subjects, 66 were successfully contacted and 52 completed the survey (79% response rate). Participant's median age was 30.7 (interquartile range (IQR) 24.9-36.9) years and most were Caucasian, college graduates, nulliparous and in a committed relationship. The median knowledge post-FPC score was 6 (IQR: 5-9). Higher knowledge scores were associated with a college education, higher income, a primary diagnosis of breast cancer, additional contact with the FP specialist following the initial FPC and use of specific reference websites such as www.fertilehope.org. Parity, marital status and completion of FP treatment were not associated with knowledge scores. CONCLUSIONS: FP knowledge following comprehensive FPC remains limited. Modifications to the current single visit FPC, such as a standard follow-up visit or additional educational tools, may be needed to improve patient comprehension of complex FP treatment options. Further research is needed to validate the knowledge scale in broader populations of cancer patients receiving FPC.

Results from the survey for preservation of adolescent reproduction (SPARE) study: gender disparity in delivery of fertility preservation message to adolescents with cancer.

PURPOSE: Diminished reproductive capacity is a devastating consequence of life-sparing therapies for childhood malignancy. In 2006, the American Society of Clinical Oncology (ASCO) published fertility preservation recommendations (ASCOR) emphasizing the importance of early discussion and intervention for fertility preservation strategies. Using the Survey for Preservation of Adolescent REproduction (SPARE), we sought to determine fertility preservation attitudes and practice patterns post-ASCOR from pediatric oncology specialists nationwide. MATERIALS AND METHODS: The SPARE survey consists of 22 questions assessing pediatric oncology specialists' attitudes and practice patterns toward fertility preservation. Broad perspectives on fertility preservation, including a willingness to discuss fertility, knowledge of current fertility preservation methods and awareness of ASCOR, were assessed. RESULTS: The majority of respondents acknowledged that fertility threats are a major concern for them and agreed that all pubertal cancer patients should be offered a fertility consultation, but only 46% reported they refer male pubertal cancer patients to a fertility specialist prior to cancer treatment >50% of the time, and only 12% reported they refer female pubertal cancer patients to a fertility specialist prior to cancer treatment > 50% of the time. While 44% of respondents were familiar with the 2006 ASCOR, only 39% of those utilized them to guide decision-making in greater than half of their patients. CONCLUSION: Our study demonstrates pediatric oncologists' motivation to preserve fertility in pediatric cancer patients; however, barriers to both gamete cryopreservation and referral to fertility specialists persist. Female pubertal patients are referred to fertility preservation specialists with much less frequency than are male pubertal patients, highlighting a disparity.

In vitro grown human ovarian follicles from cancer patients support oocyte growth.

BACKGROUND: Young female adult and adolescent cancer patients facing life-preserving but fertility-threatening chemo- or radiation-therapy are increasingly seeking options to protect their reproductive potential. Ovarian tissue cryopreservation with transplantation is a promising technique to safeguard fertility in cancer patients. However, this method may risk re-introduction of the original cancer to the survivor of the disease. Thus, developing a method for in vitro growth of immature follicles may provide a method for fertility restoration in the future. METHODS: Human secondary follicles were isolated from ovarian tissues obtained from cancer patients and grown in vitro within a bio-engineered culture system for 30 days. RESULTS: Human ovarian follicles became steroidogenically active, and developed from the early secondary to antral stage in vitro. The follicles contained healthy, growing oocytes that were connected by transzonal projections between the somatic cells and oocyte. CONCLUSIONS: Our data support the notion that human follicle development can be achieved in vitro in a bio-engineered culture system. More studies are required to investigate whether the fully sized oocytes obtained from in vitro grown follicle are competent to resume meiosis and be fertilized.

Preserving female fertility following cancer treatment: current options and future possibilities.

Children and women of reproductive age are increasingly surviving cancer diagnoses, and therefore long-term quality-of-life issues are of greater importance at the time of diagnosis. Cancer therapies including radiation and chemotherapy can be detrimental to fertility, and therefore many patients are motivated to preserve fertility prior to cancer treatment. The only highly successful method in preserving fertility to date is embryo cryopreservation, which may not be appropriate for some patients due to age, delay in treatment, cancer type and stage, as well as availability of an acceptable sperm donor. Alternative methods including oocyte cryopreservation and ovarian tissue banking may also preserve fertility while providing additional flexibility to patients. In vitro ovarian follicle maturation following tissue banking is one potential approach that would not require a delay in cancer therapy for ovarian stimulation, would not require an immediate sperm donor, and does not carry the risk of reintroducing malignant cells following tissue transplantation. In vitro follicle culture systems have resulted in successful live births in the mouse. However, many challenges must be addressed in translating the system to the human. This review summarizes current approaches to fertility preservation and discusses recent developments and future challenges in developing a human in vitro follicle culture system.

Priorities in Fertility Decisions for Reproductive-Aged Cancer Patients: Fertility Attitudes and Cancer Treatment Study.

PURPOSE: The Fertility Attitudes and Cancer Treatment Study (FACTS) aims at better understanding the reasons and priorities of young adult cancer patients making decisions for fertility preservation (FP). Identifying the factors that center around a patient's fertility decisions will support the development of educational tools for providers and improve clinical care to meet patients' reproductive needs. METHODS: An exploratory qualitative study was conducted of 27 newly diagnosed male and female cancer patients who had presented for an oncofertility consultation. Interviews lasted ∼30 minutes and were transcribed verbatim. A thematic analysis was conducted to explore the factors driving decisions for future fertility. Themes were grouped to address the following topics: reasons for/against FP, patient priorities, informational needs, support, wellness, and satisfaction with information. Strength of the theme was determined by examining the frequency of a response. RESULTS: Patients who chose FP versus those who did not choose FP and men versus women proved to be more similar than different in their reasoning, priorities, and informational needs for FP decisions. Patients who chose FP identified a "concern for future fertility" as a top reason to do so and "parenthood" as a top priority. For those who did not choose FP, "cancer treatment" was identified as their top priority. For patients identifying financial barriers, 50% of them were able to overcome this to pursue FP. CONCLUSIONS: Reproductive-aged patients diagnosed with a new cancer should be referred to a reproductive specialist and provided the opportunity to come to a fertility decision on their own before initiating cancer treatment.

A Review of the Oncology Patient's Challenges for Utilizing Fertility Preservation Services.

PURPOSE: The American Society of Clinical Oncology issued practice guidelines in 2006 to provide critical information about fertility impact to adolescents and young adults (AYA) at the time of cancer diagnosis. Survivors continue to express concerns about their long-term reproductive health after cancer therapy even as treatment options for fertility preservation evolve. An underutilization of fertility preservation methods by cancer patients continues to persist. A review of the literature cites barriers and challenges that limit fertility information and preservation options for AYA cancer patients. METHODS: A review of medical literature was conducted to examine current practice for patients receiving fertility information and the barriers to patients receiving fertility preservation services. RESULTS: A total of 69 publications were included in this review. The review summarizes (1) patient experiences with receiving fertility information and (2) patient desires, barriers, and challenges to utilizing fertility preservation services. CONCLUSIONS: Despite advances in fertility preservation, there are challenges for patients to utilizing fertility preservation services. Barriers include the following: urgency to initiate treatment, inadequate information, clinic time constraints, and perceptions around patients' gender, age, cost, parity, race, relationship, and sociodemographic status influence whether patients receive fertility preservation consultation. Patients report a lack of adequate information to make informed fertility decisions.

Do Patient Characteristics Decide if Young Adult Cancer Patients Undergo Fertility Preservation?

PURPOSE: The Fertility Attitudes and Cancer Treatment Study (FACTS) is a two-phase research initiative aimed to understand factors involved with decision making for future fertility. The FACTS will improve services and utilization of fertility preservation (FP) before cancer treatment. Phase-I examined patient characteristics as associated with FP decision. METHODS: A retrospective cohort study of 108 reproductive-aged (18-45 years) males and females who received a fertility consultation before cancer treatment from January 1, 2012 to April 30, 2014 was conducted. Chi-square, student's t-test, and logistic regression were conducted to examine associations with FP decision. RESULTS: The utilization rate of FP following fertility consultation was 49%. Gender was the most significant factor contributing to FP decision; 74% of those who choose FP were male (odds ratio = 12.5; 95% confidence interval 5.1-31.4). Those who opted for FP were more likely to be Caucasian (p = 0.042), have a solid tumor (p = 0.03), and have a shorter time from diagnosis to fertility consultation (29.5 vs. 58.8 days; p = 0.017). Age, relationship, tumor location, treatment plan, and parity were not significant predictors of FP. CONCLUSIONS: Current perceptions about patient demographics do not predict FP utilization by young adult cancer patients. Providing patients an informed fertility consultation has demonstrated an increase in FP utilization to nearly one-half of patients. Despite gender being a significant factor in choosing FP, the study did not provide reasons as to why. The phase-II study will explore patients' reasons for FP decision in a qualitative design to understand these differences.

Fertility preservation training for obstetrics and gynecology fellows: a highly desired but non-standardized experience.

BACKGROUND: Despite a large body of data suggesting that delivery of fertility care to cancer patients is inconsistent and frequently insufficient, there is a paucity of literature examining training in fertility preservation for those physicians expected to discuss options or execute therapy. The study objective was to compare fertility preservation training between Reproductive Endocrinology & Infertility (REI) and Gynecologic Oncology (GYN ONC) fellows and assess the need for additional education in this field. METHODS: A 38-item survey was administered to REI and GYN ONC fellows in the United states in April 2014. Survey items included: 1) Clinical exposure, perceived quality of training, and self-reported knowledge in fertility preservation; 2) an educational needs assessment of desire for additional training in fertility preservation. RESULTS: Seventy-nine responses were received from 137 REI and 160 GYN ONC fellows (response rate 27%). REI fellows reported seeing significantly more fertility preservation patients and rated their training more favorably than GYN ONC fellows (48% of REI fellows versus 7% of GYN ONC fellows rated training as 'excellent', p < 0.001). A majority of all fellows felt discussing fertility preservation was 'very important' but fellows differed in self-reported ability to counsel patients, with 43% of REI fellows and only 4% of GYN ONC fellows able to counsel patients 'all the time' (p = 0.002). Seventy-six percent of all fellows felt more education in fertility preservation was required, and 91% felt it should be a required component of fellowship training. CONCLUSION: Significant variability exists in fertility preservation training for REI and GYN ONC fellows, with the greatest gap seen for GYN ONC fellows, both in perceived quality of fertility preservation training and number of fertility preservation patients seen. A majority of fellows in both disciplines support the idea of a standardized multi-disciplinary curriculum in fertility preservation.

Fertility Preservation Options for Men and Women With Cancer.

Approximately 0.2% of Americans aged 20 to 39 years are childhood cancer survivors. Advances in cancer detection and therapy have greatly improved survival rates for young cancer patients; however, treatment of childhood cancers can adversely impact reproductive function. Many cancer patients report a strong desire to be informed of existing options for fertility preservation and future reproduction prior to initiation of gonadotoxic cancer therapies, including surgery, chemotherapy, and radiotherapy. This article discusses, in detail, the effects of cancer treatment on fertility in men and women, and outlines both current and experimental methods of fertility preservation among cancer patients.

Seamless integration of clinical care and research in an innovative fertility preservation program: the Colorado Oncofertility Program model.

PURPOSE: The purpose of this study is to describe a model of care for fertility preservation (FP) that integrates clinical care and research through the establishment of the Colorado Oncofertility Program's (COP) patient registry. METHODS: To integrate research and clinical care, the COP developed a multidisciplinary organizational structure and established a prospective registry of demographic information and clinical data of patients who agree to participate in future studies. RESULTS: The patient registry allows for the integration of clinical care and research as well as streamlined data collection. Since the program launch in January 2012, over 285 patients have been evaluated and >95% of approached patients have agreed to participate in the registry. Data collected are used for research, systematic program evaluation, and utilization of services. IMPLICATIONS FOR CANCER SURVIVORS: As one of the fastest growing oncofertility programs in the country, there is great potential for the COP's registry to contribute to expanding the limited body of literature on the late effects of cancer treatment on fertility and reproductive health in the adolescent and young adult (AYA) oncology population. With the use of web-based bioinformatics, objective data are captured for clinical care, future studies, program evaluation, and quality assurance, without compromising patient autonomy, privacy, and confidentiality or the commitment to personalized care.

Low birth weight: is it related to assisted reproductive technology or underlying infertility?

Since 1978, we have witnessed a successful evolution of assisted reproductive technology (ART), with improvement of the pregnancy rates and a growing demand. However, in recent years, there has been increasing concern regarding its safety due to the potential health impact on its infants. The raise of the developmental origins of adult disease has positioned low birth weight (LBW) as a significant health issue. Although multiple studies have associated ART with LBW, the etiology of this association remains largely unknown. We review the potential association between different components of ART and infertility with LBW, while acknowledging the limitations of interpretation of the existing literature.