A step closer to parenthood with non-obstructive azoospermia: Unveiling the impact of microdissection testicular sperm extraction in Australia's largest single-centre study.

BACKGROUND: Non-obstructive azoospermia (NOA) diagnosis poses challenges for couples seeking parenthood. Microdissection testicular sperm extraction (MD-TESE) excels in retrieving testicular sperm cells for NOA cases. However, limited live birth data in Australian NOA patients hinders accurate counselling. AIMS: This study aimed to determine the likelihood of infertile couples with a male partner diagnosed with NOA conceiving biological children using MD-TESE / intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: A retrospective cohort study included 108 NOA men treated at a public fertility unit and a private fertility centre (May 2009-May 2022). PRIMARY OUTCOME: live birth rate (LBR); secondary outcomes: sperm retrieval rate, pregnancy rate, and neonatal outcomes. RESULTS: Among 108 patients undergoing MD-TESE, the positive sperm retrieval rate (PSRR) was 64.8% (70/108). Histology best predicted sperm retrieval success, with hypo-spermatogenesis yielding a 94.1% PSRR. Age, testicular volume, and hormonal parameters had no significant impact. Mean male age: 35.4 years; mean partner age: 32.7 years. Fertilisation rate: 50.7%. LBR per initiated cycle: 58.7% (37/63); per embryo transfer: 63.8% (37/58); per initially diagnosed NOA man: 34.3% (37/108). Cumulative LBR: 74.1% (43/58); twin rate: 10.8% (4/37). No neonatal deaths or defects were observed among 47 live offspring. CONCLUSION: This study provides valuable data for counselling NOA couples on the probability of conceiving biological offspring. MD-TESE and ICSI yielded favourable PSRR (64.8%) and LBR (63.8%). However, couples should be aware that once NOA is confirmed, the chance of taking home a baby is 34%.

A rare case of mosaic Klinefelter syndrome in a 45-year-old man leading to successful live birth through ejaculated spermatozoa: a case report and literature review.

Background: Men diagnosed with Klinefelter syndrome (KS) commonly exhibit non-obstructive azoospermia or rarely having sperm in their ejaculate, rendering them traditionally considered sterile prior to the introduction of intracytoplasmic sperm injection (ICSI). The presence of mosaic KS may mask the classical phenotype, resulting in underdiagnosis throughout their lifetime. Surgical sperm retrieval through Microdissection Testicular Sperm Extraction (Micro-TESE) combined with ICSI has become the gold standard approach, maximizing reproductive outcomes in these individuals. However, it is noteworthy that approximately 7% of men with KS may exhibit sperm in their ejaculate, providing an opportunity for them to achieve biological parenthood through ICSI. Case Presentation: In this report, we present an exceptional case of a 45-year-old man with Mosaic KS and severe oligozoospermia who successfully achieved pregnancy utilizing ICSI with freshly ejaculated sperm. Remarkably, this case represents the oldest recorded instance of a man with Klinefelter syndrome fathering his own biological child using sperm derived from fresh ejaculate. Conclusion: Although this case is exceedingly rare, it underscores the critical importance of exhausting all possibilities to facilitate biological parenthood in men with KS before considering alternative options such as sperm donation or adoption. By recognizing the potential for successful conception using ejaculated sperm in this population, we can provide individuals with mosaic KS the opportunity to fulfill their desire for biological offspring.

Controlled ovarian hyperstimulation in breast cancer patients: Does oestrogen receptor status make a difference?

BACKGROUND: The presence of different breast cancer receptor status may impact ovarian stimulation outcomes. AIM: To study the association between oestrogen receptor (ER) status in breast cancer patients and fertility preservation outcomes in a major tertiary referral centre. MATERIALS AND METHODS: Women who underwent fertility preservation following the diagnosis of breast cancer from 2008 to 2018 were included in the study. Patient age, ovarian stimulation parameters and laboratory outcomes were recorded and compared between the ER positive and negative groups. The primary outcome was total number of oocytes frozen. Secondary outcomes included total number of oocytes collected, mature oocytes, and embryos frozen. RESULTS: The women included in the study (n = 214) were analysed in the following groups based on their fertility preservation method: oocyte freezing (n = 131), embryo freezing (n = 70), and both embryo and oocyte freezing (n = 13). There was an increase in the mean (but not mature) number of oocytes frozen (12.4 and 9.2, P-value = 0.03) favouring the ER positive group, even though the women in this group were older (35.0 and 33.4, P-value of 0.03). There is no difference in the starting follicle-stimulating hormone dose, duration of stimulation, mature oocytes collected, and embryos frozen in both groups. CONCLUSION: Patients with ER positive breast cancer may have more positive ovarian stimulation outcomes.

The development and phase 1 evaluation of a Decision Aid for elective egg freezing.

BACKGROUND: Elective egg freezing decisions are complex. We developed a Decision Aid for elective egg freezing and conducted a phase 1 study to evaluate its acceptability and utility for decision-making. METHODS: The online Decision Aid was developed according to International Patient Decision Aid Standards and evaluated using a pre/post survey design. Twenty-six Australian women aged 18-45 years, interested in receiving elective egg freezing information, proficient in English, and with access to the internet were recruited using social media and university newsletters. Main outcomes were: acceptability of the Decision Aid; feedback on the Decision Aid design and content; concern raised by the Decision Aid, and; utility of the Decision Aid as measured by scores on the Decisional Conflict Scale and on a study-specific scale assessing knowledge about egg freezing and age-related infertility. RESULTS: Most participants found the Decision Aid acceptable (23/25), balanced (21/26), useful for explaining their options (23/26), and for reaching a decision (18/26). Almost all reported satisfaction with the Decision Aid (25/26) and the level of guidance  it provided (25/26). No participant reported serious concerns about the Decision Aid, and most would recommend it to other women considering elective egg freezing (22/26). Median Decisional Conflict Scale score decreased from 65/100 (Interquartile range: 45-80) pre-Decision Aid to 7.5/100 (Interquartile range: 0-37.5) post-Decision Aid review (p < 0.001). Median knowledge score increased from 8.5/14 (Interquartile range: 7-11) pre-Decision Aid to 11/14 (Interquartile range: 10-12) post-Decision Aid review (p = 0.01). CONCLUSION: This elective egg freezing Decision Aid appears acceptable and useful for decision-making. It improved knowledge, reduced decisional conflict and did not raise serious concerns. The Decision Aid will be further evaluated using a prospective randomised control trial. STUDY REGISTRATION: ACTRN12618001685202 (retrospectively registered: 12 October 2018).

The ovarian hyperstimulation that truly matters: Admissions, severity and prevention strategies.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is a common but serious complication of in vitro fertilisation. Despite available strategies to reduce OHSS incidence, a small proportion of patients will develop the clinically significant disease with substantial morbidity. Efforts toward better understanding and the prevention of severe disease are required to improve patient outcomes. AIMS: The aims are to: (1) formulate clinically relevant OHSS classification for inpatient settings and data collection/reporting; (2) estimate OHSS prevalence requiring hospital admission in Victoria; and (3) determine the extent of OHSS preventability with clinical strategies. MATERIALS AND METHODS: This retrospective cohort study included all OHSS admissions in a tertiary referral centre, January 2016-December 2021, which included approximately 40% of all cases of hospitalisation for OHSS in the State of Victoria. Patient characteristics, treatment regimes, fertility treatment outcomes, timing classification, and clinical markers of disease severity were studied. Patients were classified as having mild, moderate, or severe OHSS with a novel inpatient classification system. RESULTS: Of 199 OHSS cases presenting to the tertiary institution, 107 were classified as moderate/severe, with no significant difference between age, body mass index, length of stimulation and follicle number between mild/moderate and severe groups. There were more cases of early hyperstimulation (137) compared to late (62) presentation, of which 53% were severe. The average length of stay overall was 3.1 days, and 5.2 days for severe presentations. In 15% of severe cases, an agonist trigger was used. CONCLUSIONS: The overall prevalence of OHSS requiring hospital admission appears to be low (approximately 0.6% of all stimulated cycles). Established risk factors may not accurately predict clinically relevant OHSS risk. Further monitoring, clinician and patient education are required to minimise the risk of significant OHSS that results in hospital admissions.

School-age outcomes among IVF-conceived children: A population-wide cohort study.

BACKGROUND: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. METHODS AND FINDINGS: Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in ≥2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects. The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of -0.3% (95% CI -3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI -0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school. CONCLUSIONS: In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians.

Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts.

Purpose: Uncertainties remain regarding the clinical efficacy of ovarian tissue cryopreservation and grafting. We report a retrospective analysis of reproductive outcomes and lessons learnt following 55 ovarian tissue transplant procedures at our center from 2006 to 2019. Methods: We analyzed variables related to graft success such as tissue volume, follicular density, total follicular volume, and age on the duration of graft function. Results: Follicular density and total follicular volume correlate positively with duration of graft function. All clinical pregnancies in our cohort occurred in women who were aged 35 or less at the time of ovarian tissue cryopreservation. Conclusion: Graft success, as determined by eventual pregnancy and the longevity of graft function, may be impacted by factors including age at cryopreservation, follicular density, and total follicular volume.

Comparing pregnancy outcomes between natural cycles and artificial cycles following frozen-thaw embryo transfers.

BACKGROUND: Frozen embryo transfer (FET) is increasing in prevalence. In contrast to the amount of research performed on the actual cryopreservation procedure, there are limited data with respect to optimal endometrial preparation in FET cycles. Increasingly artificial cycle (AC) preparation is being adopted over the natural cycle (NC) to facilitate greater access to FET. However, there remains a paucity of data comparing pregnancy outcomes between these two commonly used cycle types. AIMS: To examine the efficacy of AC vs NC following FET, by comparing pregnancy outcomes including biochemical, clinical and live birth rates, along with miscarriage rates. MATERIALS AND METHOD: This is a large single-centre retrospective analysis, examining a standardised data set from January 2015 to July 2018. It included 3030 cycles (NC = 2033, AC = 997). Main outcomes were biochemical pregnancy (beta-human chorionic gonadotropin > 5 IU), ultrasound-diagnosed clinical pregnancy, and live births. Using the χ2 test, the above pregnancy outcomes were compared between AC and NC. A multivariate logistic regression, controlling for factors such as age, embryo quality, and day of blastocyst freeze was further utilised to assess for confounding variables. RESULTS: No difference was observed between biochemical pregnancy rates (NC = 39.45% vs AC = 37.71%, P = 0.357); statistically significant differences were observed between clinical pregnancy (30.84% vs 26.08%, P = 0.007), and live birth rates (24.40% vs 18.86% P = 0.001). Multivariate analysis confirmed that NC produces superior pregnancy outcomes when controlling for confounding variables. CONCLUSION: This analysis demonstrates the non-inferiority of NC thaw compared to AC, on continuing pregnancy rates. Taken together with patient acceptability and possibly increased obstetric risks with AC, these findings support the use of NC when medically possible.

Exploring the facilitators and barriers to using an online infertility risk prediction tool (FoRECAsT) for young women with breast cancer: a qualitative study protocol.

INTRODUCTION: As cancer treatments may impact on fertility, a high priority for young patients with breast cancer is access to evidence-based, personalised information for them and their healthcare providers to guide treatment and fertility-related decisions prior to cancer treatment. Current tools to predict fertility outcomes after breast cancer treatments are imprecise and do not offer individualised prediction. To address the gap, we are developing a novel personalised infertility risk prediction tool (FoRECAsT) for premenopausal patients with breast cancer that considers current reproductive status, planned chemotherapy and adjuvant endocrine therapy to determine likely post-treatment infertility. The aim of this study is to explore the feasibility of implementing this FoRECAsT tool into clinical practice by exploring the barriers and facilitators of its use among patients and healthcare providers. METHODS AND ANALYSIS: A cross-sectional exploratory study is being conducted using semistructured in-depth telephone interviews with 15-20 participants each from the following groups: (1) premenopausal patients with breast cancer younger than 40, diagnosed within last 5 years, (2) breast surgeons, (3) breast medical oncologists, (4) breast care nurses (5) fertility specialists and (6) fertility preservation nurses. Patients with breast cancer are being recruited from the joint Breast Service of three affiliated institutions of Victorian Comprehensive Cancer Centre in Melbourne, Australia-Peter MacCallum Cancer Centre, Royal Melbourne Hospital and Royal Women's Hospital, and clinicians are being recruited from across Australia. Interviews are being audio recorded, transcribed verbatim and imported into qualitative data analysis software to facilitate data management and analyses. ETHICS AND DISSEMINATION: The study protocol has been approved by Melbourne Health Human Research Ethics Committee, Australia (HREC number: 2017.163). Confidentiality and privacy are maintained at every stage of the study. Findings will be disseminated through peer-reviewed scholarly and scientific journals, national and international conference presentations, social media, broadcast media, print media, internet and various community/stakeholder engagement activities.

Creating a Global Community of Practice for Oncofertility.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Is it possible to apply trial outcomes to a real-world population? A novel approach to External Validity Analysis.

BACKGROUND: Translation of findings from randomised controlled trials (RCT), the foundation of evidence-based medicine, into clinical practice requires an understanding of relationships between patient characteristics, treatment practices and outcomes. We propose a novel technique, External Validity Analysis (EVA), to evaluate applicability of findings from a large RCT, comparing baseline characteristics, interventions and outcomes between the RCT and a large clinical database. AIM: To perform EVA of the findings of a randomised controlled trial (ESTHER-1) to a population in an Australian clinic setting. To demonstrate this method, we evaluated the discordance in first cycle follicle-stimulating hormone (FSH) exposure and outcomes between the two populations, to inform clinical practice. MATERIALS AND METHODS: In this retrospective, descriptive analysis, we compared practices and outcomes between the follitropin alfa 'conventional' dosing arm of the ESTHER-1 trial and a selected comparable clinic subpopulation of patients who underwent controlled ovarian stimulation using FSH. RESULTS: Mean FSH exposure was 34% higher in the clinic subpopulation than in the trial subpopulation, resulting in higher average ovarian response without improving the likelihood of clinical pregnancy or live birth. CONCLUSIONS: EVA allowed for the comparison of a trial population with a selected clinic population with similar characteristics. With respect to FSH consumption, this analysis revealed higher exposure to FSH in the clinic setting without a corresponding benefit. The comparison reveals population differences as well as the potential to improve clinical outcomes through a reappraisal of current practices and objectives in gonadotropin dose selection.

The incidence of hypertensive disorders of pregnancy following sperm donation in IVF: an Australian state-wide retrospective cohort study.

STUDY QUESTION: Does IVF using donor sperm increase the risk of hypertensive disorders of pregnancy and fetal growth restriction (FGR)? SUMMARY ANSWER: IVF conceptions arising from sperm donation are not associated with an increased risk of hypertensive disorders of pregnancy or FGR. WHAT IS KNOWN ALREADY: It has been hypothesized that the absence of prior exposure to factors within the paternal ejaculate increases the risk of preeclampsia and FGR among nulliparous women or women with a new partner-the concept of 'primipaternity'. It remains unclear which element of the ejaculate is responsible: the sperm cell or the constituents of seminal fluid. IVF pregnancies arising from donor sperm where the seminal fluid is absent provide a unique opportunity to test the theory of primipaternity and the relative contribution of the sperm cell. Pregnancies conceived via artificial reproductive technology are at increased risk of preeclampsia and FGR. STUDY DESIGN, SIZE, DURATION: Theories about the development of preeclampsia and the relative contribution of spermatic factors were explored by comparing the risk of hypertensive disorders of pregnancy and FGR among IVF pregnancies conceived with autologous gametes (own eggs and partner sperm) and those conceived with donor sperm, donor egg (and partner sperm) and donor embryo. To do this, we performed a retrospective cohort analysis of pregnancy outcomes among singleton pregnancies (n = 15 443) conceived through fertility clinics within Australia between 2009 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: All pregnancies resulting in a singleton pregnancy delivering after 20 weeks' gestation were included. The cohort was divided into donor sperm, donor egg and donor embryo (where both gametes came from a donor to create an embryo, or in a surrogate pregnancy) groups. We also compared the data with a control group, defined as IVF-conceived pregnancies from autologous cycles. A multivariable regression model was used to calculate an adjusted odds ratio (aOR). MAIN RESULTS AND THE ROLE OF CHANCE: The final cohort contained 1435, 578 and 239 pregnancies conceived by donor sperm, donor egg and donor embryo, respectively, and 13 191 controls. There were a very small number of women lost to follow-up (31 women; 0.2% of total cohort). Compared to control pregnancies, there was no increase in the risk of hypertensive disorders among pregnancies conceived via donor sperm (aOR 0.94; 95% CI 0.73-1.21). Subgroup analysis was performed for a cohort where parity was known (n = 4551), and of these, 305 multigravida pregnancies were conceived via donor sperm. Among this cohort, no increased risk of preeclampsia or pregnancy-induced hypertension was found (aOR 1.18; 95% CI: 0.69-2.04) as a result of primipaternity (new sperm donor).A significantly increased risk for hypertensive disorders of pregnancy was associated with the use of donor eggs (but partner sperm; aOR 2.34; 95% CI 1.69-3.21). However, the association was no greater among pregnancies conceived with donor embryos (i.e. donated egg and sperm; aOR 2.0; 95% CI 1.25-3.17) than among the donor oocyte group. The overall incidence of FGR (defined as birthweight <10th centile) was 18%. There were no significant differences observed between donor sperm, or donor embryo pregnancies; however, egg donation was associated with a 1.5-fold increase in FGR. LIMITATIONS, REASONS FOR CAUTION: This study was limited by a lower than expected rate of hypertensive disorders of pregnancy (n = 862, 5.6%), which is contrary to the well-established increased risk among women using IVF. However, this is likely to be evenly distributed across the study groups and, therefore, unlikely to have introduced significant bias. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that exposure to new sperm may not be implicated in the pathogenesis of preeclampsia. The mechanism of increased risk seen in conceptions arising from egg or embryo donation remains unclear. Further investigation is required to elucidate these mechanisms and, ultimately, improve pregnancy outcomes following IVF. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Australian Commonwealth Government-Graduate Research Scheme (A.K.). Salary support was provided by the National Health and Medical Research Council of Australia (S.T.), Mercy Foundation (A.L.), and the Department of Obstetrics and Gynaecology at the University of Melbourne (R.H.). There are no competing interests.

Satisfaction, disappointment and regret surrounding fertility preservation decisions in the paediatric and adolescent cancer population.

PURPOSE: With over 80% of paediatric and adolescent cancer patients surviving into adulthood, quality-of-life issues such as future fertility are increasingly important. However, little is known about regret around decisions to pursue or forgo fertility preservation (FP). We investigated the risk of decision regret in families involved in making a FP decision and explored contributive factors. METHODS: Parents and patients ≥ 15 years were invited to participate. Participants completed a 10-item survey, including a validated Decision Regret Scale. Scores ≥ 30 indicated high regret. Free-text response items allowed participants to provide reasons for satisfaction or regret. RESULTS: A total of 108 parents and 30 patients participated. Most (81.4%) reported low regret (mean score 13.7). On multivariate analysis, predictors of low regret included having a FP procedure and a fertility discussion pre-treatment. Most participants believed that FP offers hope for future fertility. Some reported dissatisfaction with the process of decision-making. CONCLUSION: Overall levels of regret in the study population were low, with factors associated with quality, timely discussion and belief in the success of FP technology being predictors of low regret. However, dissatisfaction with the decision-making process itself revealed that refinements to the programme are required to meet families' needs.

Use of intracytoplasmic sperm injection (ICSI) in normospermic men may result in lower clinical pregnancy and live birth rates.

BACKGROUND: While intracytoplasmic sperm injection (ICSI) was developed for overcoming male infertility, it is increasingly being used for non-male factor indications, without consensus regarding the safety and efficacy of this approach. AIMS: To determine whether ICSI offers any benefit compared to standard in vitro fertilisation (IVF), in the setting of normal semen parameters. MATERIALS AND METHODS: Retrospective analysis of reproductive outcomes in 3363 stimulated cycles (IVF = 1661; ICSI = 1702), in patients treated between 2009-2015, was performed. Selected couples had no male factor infertility. Couples with abnormal semen parameters (based on WHO 2010 guidelines), presence of anti-sperm antibodies and low oocyte yield of ≤4 oocytes, were excluded. The outcomes analysed included: (1) fertilisation rate (FR); (2) clinical pregnancy rate (CPR); and (3) live birth rate (LBR), by method of fertilisation used (IVF vs ICSI) and controlling for significant confounders. RESULTS: FR, CPR and LBR were significantly higher in the IVF group compared with ICSI (67.1% vs 62.3%, 23.06% vs 16.8%, 17.22% vs 13.2%, respectively). Pregnancy rate with ICSI was approximately 30% lower than with IVF, even when controlling for significant factors such as day of embryo transfer and number of embryos transferred. This translates to one less pregnancy in every 15 cycles where ICSI was used without clear indication. CONCLUSIONS: Our data suggest that ICSI may be detrimental to clinical outcomes and contributes to the wider understanding of use of ICSI in normospermic men.

Does nifedipine improve outcomes of embryo transfer?: Interim analysis of a randomized, double blinded, placebo-controlled trial.

BACKGROUND: Implantation failure is the main factor affecting the success rate of in vitro fertilization (IVF) procedures. Studies have reported that uterine contractions (UC) at the time of embryo transfer (ET) were inversely related to implantation and pregnancy rate, hence reducing the success of IVF treatments. Various pharmacological agents, with the exception of calcium channel blockers, have been investigated to improve ET outcomes by reducing UC. Thus, a double-blinded randomized, placebo-controlled trial was conducted to determine whether nifedipine, a calcium channel blocker with potent smooth muscle relaxing activity and an excellent safety profile, can improve the outcome of patients undergoing ET treatments. METHODS: Ninety-three infertile women were recruited into 1 of 2 groups: placebo (n = 47) or nifedipine 20 mg (n = 46). Study participants were admitted 30 minutes prior to ET and given either tablet after their baseline vital signs were recorded. They then underwent ET and were observed for adverse events for another 30 minutes post-ET. Follow up of the participants' outcomes was conducted via electronic medical records. The primary outcomes are implantation and clinical pregnancy rates. Secondary outcomes include any maternal or fetal adverse events, miscarriage, pregnancy, live births, and neonatal outcomes. Resulting data were then analyzed using t test, Pearson chi-square test, and Fisher exact test to compare outcomes between the 2 groups. RESULTS: No statistical differences in the implantation rate (42.6% vs 39.1%, P = .737, rate ratio 0.868, 95% confidence interval [CI]: 0.379-1.986) and the clinical pregnancy rate (23.4% vs 26.1%, P = .764, rate ratio 1.155, 95% CI: 0.450-2.966) were detected between the placebo and the treatment groups. In addition, no statistical significance between the placebo and the treatment groups for any secondary outcomes were detected. CONCLUSIONS: This double blinded, randomized, and placebo-controlled trial demonstrated that the single use of 20 mg nifedipine given 30 minutes before embryo transfer did not improve the implantation rate or the clinical pregnancy rate of the infertility treatment. Further studies are required to demonstrate the clinical benefits and risks of nifedipine usage in embryo transfer.

Setting up a fertility preservation programme.

With improved survival rates from cancer, young people can expect to lead a normal life, including having their own children. However, cancer or other serious disease itself, and more often its treatment, often leads to a significant reduction in fertility or premature gonadal insufficiency. There is increasing acknowledgement for the importance of fertility preservation (FP) options to be discussed and offered to young people whose fertility is at risk, ideally before the gonadotoxic therapy begins. FP options currently include oocyte, embryo and ovarian tissue cryopreservation; ovarian protection during chemotherapy and semen, sperm and testicular tissue cryopreservation. A multidisciplinary team consisting of committed and enthusiastic doctors, scientists, nurses, counsellors, administrators and researchers is required to provide a holistic FP service with rapid response capacity for acute consultation and procedures and a robust system for long-term follow-up. This speciality is developing rapidly with exciting scientific advances that have relevance for the whole spectrum of reproductive medicine.

A short report on current fertility preservation strategies for boys.

BACKGROUND: Advances in cancer treatment have led to improved long-term survival after childhood cancer, but often at a price of impaired future fertility. Fertility preservation (FP) in male children and early adolescents poses unique challenges as efficacy is unproven. OBJECTIVES: To describe characteristics of testicular tissue cryopreservation (TTCP) specimens taken from paediatric and adolescent patients, stratified by age, and prior chemotherapy, if any, and to demonstrate evidence for germ cells. MATERIALS AND METHODS: Retrospective review of gonadal biopsies and clinical records of patients consented into the Royal Children's Hospital FP programme between 1987 and 2015. Tissue was sliced into blocks, with one section sent for histopathology prior to cryopreservation. In boys ≥12 years where spermatogenesis could be expected, a portion of tissue was disaggregated completely to look for mature sperm and if found, additional tissue was dissected and the resulting suspension frozen. RESULTS: Testicular tissue cryopreservation specimens in 44 males (0.3-16.8 years) provided an average of 7.8 slices per patient. All the specimens were taken at the same time as another necessary surgical procedure, under one general anaesthesic. There was only one complication of scrotal wound dehiscence. Seven of the forty-four (15.9%) patients had chemotherapy prior to testicular biopsy, while the rest were chemotherapy naïve. Five of these were prepubertal, and two were pubertal patients. Eleven subjects had tissue dissected with mature sperm found in eight. Of these eight patients where sperm were found, all were pubertal with testicular size of more than 10 mL and showing histological evidence of spermatogenesis. No histologic specimen demonstrated any malignant cells. CONCLUSIONS: Testicular tissue cryopreservation can be performed in young patients without delay, preferably prior to cancer treatment. As testicular tissue contains germ cells from which haploid spermatozoa are ultimately derived, future technologies may allow their utilization for fertility in humans. This may be the only hope for biological offspring in some patients undergoing fertility compromising treatment. Retrieval of mature sperm from some pubertal patients, however, offers realistic hope to these patients of future fertility.

Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.

STUDY QUESTION: What are the reproductive experiences of women who cryopreserve oocytes for non-medical reasons? SUMMARY ANSWER: One in three women had been pregnant at some stage in their lives and while most still wanted to have a child or another child, very few had used their stored oocytes, predominantly because they did not want to be single parents. WHAT IS KNOWN ALREADY: The number of healthy women who freeze oocytes to avoid age-related infertility is increasing. Evidence about reproductive outcomes after oocyte cryopreservation for non-medical reasons is needed to help women make informed decisions. STUDY DESIGN SIZE, DURATION: A cross-sectional survey was carried out. Study packs which included a self-administered questionnaire were mailed by clinic staff to 193 eligible women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who had stored oocytes for non-medical reasons at Melbourne IVF, a private ART clinic, between 1999 and 2014 were identified from medical records and invited to complete an anonymous questionnaire about their reproductive histories and experience of oocyte cryopreservation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 10 survey packs were returned to the clinic marked 'address unknown'. Of the 183 potential respondents, 96 (53%) returned the questionnaire. One respondent provided only free-text comments, thus data from 95 respondents were compiled. The mean age at the time of freezing oocytes was 37.1 years (SD ± 2.6, range: 27-42) and the average number of oocytes stored was 14.2 (SD ± 7.9, range: 0-42); 2% had attempted to store oocytes but had none suitable for freezing, 24% had stored <8 oocytes, 35% had 8-15, 25% had 16-23 and 14% had stored >23 oocytes. About one-third of respondents (34%) had been pregnant at some point in their lives. Six women (6%) had used their stored oocytes and three of them had given birth as a result. The main reason for not using stored oocytes was not wanting to be a single parent. Of the 87 (91%) women who still had oocytes stored, 21% intended to use them while 69% indicated that their circumstances would determine usage. The mean number of children respondents would ideally have liked to have was significantly higher than the number of children they expected to have (2.11 versus 1.38, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The limitations are inherent to any anonymously completed questionnaire: participation bias, missing data and the possibility that some questions or response alternatives may have been ambiguous. WIDER IMPLICATIONS OF THE FINDINGS: The findings add to the very limited evidence about the reproductive outcomes experienced by women who freeze oocytes for non-medical reasons and can be used to help women make informed decisions about whether to store oocytes. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Melbourne IVF. K.H. has received honoraria from Merck-Serono, J.M. is a clinician at Melbourne IVF, F.A. is a Melbourne IVF employee, J.F. is supported by a Monash Professorial Fellowship and the Jean Hailes Professorial Fellowship which receives funding from the L and H Hecht Trust, managed by Perpetual Trustees Pty Ltd. M.K., N.P., M.H., M.P. and C.B. have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Characteristics and circumstances of women in Australia who cryopreserved their oocytes for non-medical indications.

OBJECTIVE: This study aimed to explore the characteristics and circumstances of women who cryopreserved their oocytes for non-medical indications and their reasons for cryopreservation. BACKGROUND: Oocyte cryopreservation for non-medical reasons is becoming increasingly common. Little is known about women who freeze their oocytes in this context. METHODS: All women who had cryopreserved oocytes for non-medical indications at a large Australian fertility treatment centre from 1999 to 2014 were invited to complete an anonymous postal survey. RESULTS: Of the 193 questionnaires mailed, 10 were returned to sender; 96/183 (53%) were completed and returned. Most respondents had completed tertiary education (90%) and were employed in professional occupations (89%). At the time of oocyte cryopreservation, 48% of women were aged at least 38 years (range 28-44 years). Most (90%) women were single when their oocytes were frozen. The lack of a partner or having a partner unwilling to commit to fatherhood were the most common reasons for oocyte freezing, which was viewed as an investment in hope against the possibility of remaining in these predicaments. Some women reported that discussions in the media and interactions with peers influenced their decisions. A few women were influenced by tests indicating a low ovarian reserve. CONCLUSION: These data provide new evidence about women's characteristics, circumstances, and reasons for oocyte cryopreservation for non-medical indications that do not support pejorative conceptualisations of these women as selfish and hedonistic.