How can fertility counseling be implemented for every newly diagnosed pediatric patient facing gonadotoxic treatment?-A single-center experience.

Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.

The validity of the subsequent pregnancy index score for fertility-sparing trachelectomy in early-stage cervical cancer.

OBJECTIVE: To evaluate timing and a prediction model for pregnancy in early-stage cervical cancer patients who underwent fertility-sparing trachelectomy. DESIGN: Retrospective cohort. SETTING: Academic multicenter. PATIENT(S): Women ages <45 years with clinical stage I-II cervical cancer were enrolled between 2009 and 2013 (n = 393). INTERVENTION(S): Planned fertility-sparing trachelectomy. MAIN OUTCOME MEASURE(S): Cumulative incidences and clinicopathological characteristics of those who developed subsequent pregnancy were examined. RESULT(S): There were 77 (21.6%) women who had subsequent pregnancies after fertility-sparing trachelectomy with 1-, 2-, and 5-year cumulative pregnancy rates of 2.8%, 6.2%, and 17.4%, respectively. The median time to develop subsequent pregnancy was 3.2 years. In a competing risk analysis, women had a higher risk of recurrent cancer than conception during the first 11 months postsurgery. On multivariable analysis, younger age, being married, and postoperative reproductive treatment were independently associated with an increased chance of developing a subsequent pregnancy. The subsequent pregnancy index (SPI) score to predict the likelihood of having pregnancy was proposed, and it was calculated based on age, marital status, and reproductive treatment (2, 2, and 4 points, respectively). Women with a higher SPI score had significantly higher subsequent pregnancy rates (5-year pregnancy rate; the score was 3 in 4.7% of cases; 4 to 5 in 11.3%; 6 to 7 in 27.4%; and 8 in 50.8%), but they had similar recurrence rates (5.0%). CONCLUSION(S): The SPI score proposed in our study is useful in predicting subsequent pregnancy in women with early-stage cervical cancer undergoing fertility-sparing trachelectomy.

A novel mathematical model of true ovarian reserve assessment based on predicted probability of poor ovarian response: a retrospective cohort study.

PURPOSE: To establish a mathematical model for assessing the true ovarian reserve based on the predicted probability of poor ovarian response (POR). METHODS: In this retrospective cohort study, a total of 1523 GnRH-antagonist cycles in 2017 were firstly analyzed. The ovarian responses were calculated based on the number of retrieved oocytes. The continuous variables were converted into categorical variables according to cutoff values generated by the decision tree method. The optimal model was identified using forward stepwise multiple logistic regression with 5-fold cross-validation and further verified its performances using outer validation data. RESULTS: The predictors in our model were anti-Müllerian hormone (AMH), antral follicle counts (AFC), basal follicle-stimulating hormone (FSH), and age, in order of their significance, named AAFA model. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value of AAFA model in inner validation and outer validation data were 0.861 and 0.850, 0.603 and 0.519, 0.917 and 0.930, 0.655 and 0.570, and 0.899 and 0.915. Ovarian reserve of 16 subgroups was further ranked according to the predicted probability of POR and further divided into 4 groups of A-D using clustering analysis. The incidence of POR in the four groups was 0.038 (0.030-0.046), 0.139 (0.101-0.177), 0.362 (0.308-0.415), and 0.571 (0.525-0.616), respectively. The order of ovarian reserve from adequate to poor followed the order of A to D. CONCLUSION: We have established an easy applicable AAFA model for assessing true ovarian reserve and may have important implications in both infertile women and general reproductive women in Chinese or Asian population.

Challenges of fertility preservation in non-oncological diseases.

Clinicians should provide fertility counseling to all patients receiving gonadotoxic treatment. International scientific societies have mainly focused on oncological patients, and fewer efforts have been made to apply these recommendations to women diagnosed with benign disease (eg benign hematological diseases, autoimmune diseases, and gynecological or genetic disorders). However, these indications account for 8%-13% of the demand for fertility preservation. The risk of premature ovarian failure due to treatment, or to the disease itself, can be considered fairly high for many young women. Counseling and adequate management of these women require particular attention due to the severe health conditions that are associated with some of these diseases. In this review, we address specific issues related to providing adequate fertility counseling and management for women who have been diagnosed with the major non-oncological indications, based on the literature and on our clinical experience.

Recent advances in fertility preservation and counseling for female cancer patients.

INTRODUCTION: Ensuring quality of life for increasing numbers of women surviving cancer has become a key challenge. Patients need to be counseled on potential fertility loss resulting from gonadotoxic treatments, and referred to fertility specialists to discuss existing options and available results. Areas covered: Fertility preservation options have existed for over twenty years. The proposed fertility preservation approach depends on patient age, the urgency of required chemotherapy, and psychosocial factors such as financial concerns, especially in countries where techniques are not covered by social security. Efficacy in terms of pregnancy rates has been demonstrated with frozen-thawed embryos, oocytes and re-implanted ovarian tissue. Appropriate counseling by oncologists is on the increase, despite persistently low rates of referral to fertility specialists. Expert commentary: Access to oncofertility services is steadily improving, facilitated by the growing involvement of public healthcare systems and sustained efforts all over the world to establish specific oncofertility programs. Early referral to reproductive specialists before initiation of chemo/radiotherapy is crucial to success in the field of female fertility preservation. In the near future, efforts should focus on increasing patient referrals and establishing international registries on short- and long-term outcomes of fertility preservation strategies.

Fertility Preservation in Breast Cancer.

As more young women survive breast cancer, fertility preservation (FP) is an important component of care. This review highlights the importance of early pretreatment referral, reviews the risks of infertility associated with breast cancer treatment, and defines existing and emerging techniques for FP. The techniques reviewed include ovarian suppression, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation and transplantation. The barriers women face, such as not being appropriately referred and the costs of treatment, also are addressed. Multidisciplinary, patient-centered care is essential to discussing FP with patients with breast cancer and ensuring appropriate care that includes quality of life in survivorship.

Measuring health-related quality of life in women with endometriosis: comparing the clinimetric properties of the Endometriosis Health Profile-5 (EHP-5) and the EuroQol-5D (EQ-5D).

STUDY QUESTION: Which of the Endometriosis Health Profile-5 (EHP-5) and the EuroQol-5D (EQ-5D) is the most efficient to assess quality of life in women suffering from endometriosis? SUMMARY ANSWER: Although EHP-5 and EQ-5D instruments had an excellent responsiveness, EHP-5 has a better discriminative ability than EQ-5 to measure health-related quality of life (HrQoL). WHAT IS KNOWN ALREADY: Proper measurement of HrQoL is important in endometriosis. While many quality of life instruments are available, few have been completely validated in endometriosis. The EHP-5 and the EQ-5D are short and practical scales, which may be useful. Literature is lacking to determine which one is the most suitable in clinical practice or in clinical research. STUDY DESIGN, SIZE, DURATION: This prospective and observational study conducted between 1 January 2012 and 31 December 2013 included a total of 253 consecutive women with proven endometriosis, undergoing medical or surgical treatment, in 2 French tertiary care centers. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Women over 18 years consulting for painful symptoms of at least 3 months' duration or for infertility, with endometriosis proven histologically or radiologically, were requested to fill in the 2 scales before (T0) and 12 months after treatment (T1). Construct validity consisted in testing presupposed relationships between the scales and the characteristics of the patients or the endometriosis. Responsiveness to change was calculated for all patients and in each treatment group. Effect sizes were used according to Cohen's d method. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 216 women filled in completely all the questionnaires at T0 and 133 (61.6%) at T1. EHP-5 and EQ-5D had good discriminative abilities regarding the patients' symptoms, with significant superiority of EHP-5 concerning three of the nine hypotheses. The largest difference was that calculated for the 'intensity of dysmenorrhea' using the Visual Analogic Scale, with respectively effect size from Cohen's d (ES) = 0.86 95% CI (0.54-1.17) for EHP-5 versus 0.48 95% CI (0.16-0.79) for EQ-5D. There were no differences in EHP-5 or in EQ-5D scores between subgroups according to the characteristics of endometriosis. Overall responsiveness was excellent and equivalent for EHP-5 and for EQ-5D, with, respectively, ES = 0.81 95% CI (0.56-1.56) versus ES = 0.95 95% CI (0.68-1.20). In subgroup analyses, EHP-5 was responsive in case of medical treatment with ES = 0.93 95% CI (0.07-1.70), whereas EQ-5D was not, ES = 0.73 95% CI (-0.06-1.47). LIMITATIONS, REASONS FOR CAUTION: Our study population included patients with symptomatic and mainly severe forms of endometriosis, which may suggest a spectrum bias. The evaluation of responsiveness in case of medical treatment was based on a small number of patients, which limits the interpretation of the difference found between the two scales in this subgroup. WIDER IMPLICATIONS OF THE FINDINGS: EHP-5 is a simple, efficient and valid tool for evaluating quality of life in daily practice and also valuable to provide a primary outcome in clinical studies evaluating treatment efficacy. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Direction à la Recherche Clinique et à l'Innovation of Versailles, France. The authors have no conflicts of interest. TRIAL REGISTER NUMBER: None.

Female fertility preserving practices at a pediatric unit: a challenge of multiprofessional and multidisciplinary cooperation.

INTRODUCTION: Being able to have children could have an important positive effect on the future lives of pediatric cancer survivors. Working at a cancer institute makes us responsible for filling the gaps in our knowledge in this area of patient care. METHODS: We describe our activities in a series of young females diagnosed with cancer and evaluated for fertility preservation options. We discuss the developed skills and organization as well as the practical difficulties encountered in managing fertility preservation. RESULTS: Since September 2012, laparoscopy and cryopreservation of cortical ovarian tissue has been performed in 16 girls (with ovary transposition in 3, and after several cycles of chemotherapy in 5) and egg banking in 4 young women (before chemotherapy in 2 and several years after treatment in 2). CONCLUSIONS: Recommendations on fertility preservation indicate that discussing the problems early on is crucial to future success. It is unthinkable to simply provide information and offer the opportunity to choose a fertility preserving technique without helping and accompanying patients and their families in their decisions and choices on the matter.

Preoperative assessment and diagnosis of endometriosis: are we any closer?

PURPOSE OF REVIEW: The management of endometriosis has progressed vastly with medical treatments providing a large role in controlling endometriosis symptoms. Despite these advances we still lack an accurate noninvasive test to diagnose endometriosis. This has a large role in the delay to diagnosis, management and progression of the disease amongst a population that is choosing to conceive later. RECENT FINDINGS: Endometriosis is now thought to affect 1 in 10 women with patient annual healthcare costs estimated at &OV0556;9579. The diagnosis of this disease is still delayed by an average of 6-9 years allowing disease and symptom progression. Researchers have assessed a wide variety of noninvasive markers from urinary derivatives to MRI. There has been limited success in producing a highly sensitive and specific preoperative test for endometriosis. Novel markers such as miRNA provide the most encouraging diagnostic accuracy. SUMMARY: The development of a noninvasive accurate marker for endometriosis is a research target and priority of the European Society of Human Reproduction and Embryology. The current markers in use have moderate sensitivity and sensitivity. The inflammatory basis for the disease underpins many biomarkers but also many other concomitant diseases reducing accuracy and increasing false positive results.

Infertility in reproductive-age female cancer survivors.

Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program.

Impact and cost-effectiveness of chlamydia testing in Scotland: a mathematical modelling study.

BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection in Scotland, and is associated with potentially serious reproductive outcomes, including pelvic inflammatory disease (PID) and tubal factor infertility (TFI) in women. Chlamydia testing in Scotland is currently targeted towards symptomatic individuals, individuals at high risk of existing undetected infection, and young people. The cost-effectiveness of testing and treatment to prevent PID and TFI in Scotland is uncertain. METHODS: A compartmental deterministic dynamic model of chlamydia infection in 15-24 year olds in Scotland was developed. The model was used to estimate the impact of a change in testing strategy from baseline (16.8% overall testing coverage; 0.4 partners notified and tested/treated per treated positive index) on PID and TFI cases. Cost-effectiveness calculations informed by best-available estimates of the quality-adjusted life years (QALYs) lost due to PID and TFI were also performed. RESULTS: Increasing overall testing coverage by 50% from baseline to 25.2% is estimated to result in 21% fewer cases in young women each year (PID: 703 fewer; TFI: 88 fewer). A 50% decrease to 8.4% would result in 20% more PID (669 additional) and TFI (84 additional) cases occurring annually. The cost per QALY gained of current testing activities compared to no testing is £40,034, which is above the £20,000-£30,000 cost-effectiveness threshold. However, calculations are hampered by lack of reliable data. Any increase in partner notification from baseline would be cost-effective (incremental cost per QALY gained for a partner notification efficacy of 1 compared to baseline: £5,119), and would increase the cost-effectiveness of current testing strategy compared to no testing, with threshold cost-effectiveness reached at a partner notification efficacy of 1.5. However, there is uncertainty in the extent to which partner notification is currently done, and hence the amount by which it could potentially be increased. CONCLUSIONS: Current chlamydia testing strategy in Scotland is not cost-effective under the conservative model assumptions applied. However, with better data enabling some of these assumptions to be relaxed, current coverage could be cost-effective. Meanwhile, increasing partner notification efficacy on its own would be a cost-effective way of preventing PID and TFI from current strategy.

Robotic surgery for early stage cervical cancer: Evolution and current trends.

The management of early stage cervical cancer often includes surgery in the form of radical hysterectomy, radical trachelectomy, or radical parametrectomy. Surgical techniques have evolved to include minimal invasive approaches, and more recently, to include robotic assisted techniques. This review highlights the evolution of surgical management of early cervical cancer and specifically explores robotic assisted radical hysterectomy, radical trachelectomy, radical parametrectomy, and the role of neoadjuvant chemotherapy.

Fertility awareness among medical and non-medical students: a case-control study.

BACKGROUND: To compare the understanding and perceptions of fertility issues among medical and non-medical University students. METHODS: In a prospective case-control study, using a 43 item questionnaire with 5 sections and 43 questions regarding personal data (8 questions), lifestyle factors (9 questions), plans on having children (5 questions), age and fertility (5 questions), and lifestyle and fertility (16 questions), knowledge of fertility and influencing factors, desired age at commencement and completion of childbearing, among male and female medical and non-medical students in their first academic year at Vienna University, Vienna, Austria were evaluated. RESULTS: 340 students were included. 262/340 (77%) participants planned to have children in the future. Medical students (n = 170) planned to have fewer and later children and had a higher awareness of the impact of age on fertility than non-medical students (n = 170; estimated knowledge probability 0.55 [medical students] vs. 0.47 [non-medical students]; F (1, 336) = 5.18 and p = .024 (η p = .015). Gender did not independently affect estimated knowledge probability (F (1, 336) = 1.50 and p = .221). More female and male medical students had a positive attitude towards Assisted Reproductive Technology in case of infertility than non-medical students (47 and 55% vs. 23 and 29%, respectively; p = <.001). Medical students had a healthier lifestyle than non-medical students. A healthy lifestyle and female gender were associated with higher fertility awareness. CONCLUSIONS: Medical students have a higher awareness of fertility issues than non-medical students. Choice of academic study, gender, and personal life style are important factors affecting fertility awareness. These data may be helpful to address knowledge gaps among young non-medical Academics.

Exposure to toxic environmental agents.

: Reducing exposure to toxic environmental agents is a critical area of intervention for obstetricians, gynecologists, and other reproductive health care professionals. Patient exposure to toxic environmental chemicals and other stressors is ubiquitous, and preconception and prenatal exposure to toxic environmental agents can have a profound and lasting effect on reproductive health across the life course. Prenatal exposure to certain chemicals has been documented to increase the risk of cancer in childhood; adult male exposure to pesticides is linked to altered semen quality, sterility, and prostate cancer; and postnatal exposure to some pesticides can interfere with all developmental stages of reproductive function in adult females, including puberty, menstruation and ovulation, fertility and fecundity, and menopause. Many environmental factors harmful to reproductive health disproportionately affect vulnerable and underserved populations, which leaves some populations, including underserved women, more vulnerable to adverse reproductive health effects than other populations. The evidence that links exposure to toxic environmental agents and adverse reproductive and developmental health outcomes is sufficiently robust, and the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine join leading scientists and other clinical practitioners in calling for timely action to identify and reduce exposure to toxic environmental agents while addressing the consequences of such exposure.

Status of adolescent pelvic inflammatory disease management in the United States.

PURPOSE OF REVIEW: Pelvic inflammatory disease (PID) is a common and serious reproductive health disorder and disease rates remain unacceptably high among adolescent girls and young adult women in the United States. Despite data demonstrating that women experience major adverse health outcomes after PID, national recommendations for management of adolescents have become increasingly less cautious in an era of cost-containment. In this review, we take an alternative look at published data on adolescents with PID to frame the next steps for optimizing management for this vulnerable population. RECENT FINDINGS: Several findings emerge from review of the literature. First, there is limited evidence to guide the best practice strategies for adolescents with PID due to low enrolment of early and middle adolescents in national trials. Second, adolescents and adult women in the United States receive suboptimal treatment regimens per Centers for Disease Control and Prevention (CDC) standards. Third, available evidence suggests that adolescents are at an increased risk for poor adherence to CDC recommendations for self-care, reacquisition of sexually transmitted infections (STIs) and PID, and subsequent adverse reproductive health outcomes. SUMMARY: Efforts to develop and integrate adolescent-focused, evidence-based strategies for PID management and prevention of subsequent STIs and recurrent PID are warranted.