Contraception for women over 40: A comprehensive guide.

BACKGROUND: Women in their 40s experience significant reproductive health changes, requiring personalised contraception to avoid unintended high-risk pregnancies and adapt to changing health conditions. OBJECTIVE: This article examines optimal contraceptive choices for women in their 40s, considering effectiveness, ease of use, non-contraceptive benefits, side effects, contraindications and re-evaluation or discontinuation timings. DISCUSSION: Contraceptive choices for women in their 40s vary depending on their family planning status, underlying health conditions and risk factors. Long-acting reversible contraceptives, permanent sterilisation and progestogen-only methods (excluding depot medroxyprogesterone acetate) are preferred options for women who have completed their families. Hormonal contraceptives can help manage menstrual disorders and bone health issues while providing endometrial protection during menopause. Regular contraceptive reviews should be conducted, and options adapted as needed.

Contraception options during pubertal transition: Risks, benefits and considerations.

BACKGROUND: The age of puberty and sexual maturation has been decreasing, highlighting the importance of providing appropriate contraception to girls and adolescents. However, challenges remain, including legal implications and understanding the effects of hormonal methods on pubertal development. OBJECTIVE: This article aims to equip general practitioners with the knowledge of options, as well as their use and limitations, in young people seeking contraception. DISCUSSION: No one-size-fits-all approach exists for adolescent contraception. Long-acting reversible contraceptives offer superior contraceptive efficacy, with subdermal implants being the most acceptable regarding the insertion procedure. Condoms should be recommended for protection against sexually transmissible infections. Bone health and mood disorders should be considered when prescribing hormonal contraceptives. Despite the lack of robust evidence regarding harm caused by contraception in adolescents, preventing unintended pregnancies should take precedence, with theoretical risks guiding tailored options for individuals.

Progesterone-modified natural cycle preparation for frozen embryo transfer.

RESEARCH QUESTION: Is there any difference in clinical outcomes between the progesterone-modified natural cycle (P4mNC) and hormone replacement therapy (HRT) endometrial preparation protocols after single euploid blastocyst frozen embryo transfer (FET) cycles? DESIGN: A retrospective cohort study was performed at a single, private, high-volume fertility centre. Patients who underwent single euploid blastocyst FET between January 2017 and December 2019 were included. A total of 1933 FET cycles were reviewed, and 723 FET cycles from 548 patients met the inclusion criteria. Two groups were compared according to endometrial preparation: 327 P4mNC-FET and 396 HRT-FET cycles. The primary outcome was the live birth rate. The secondary outcomes included the clinical pregnancy rate and the miscarriage rate. RESULTS: There were no differences in the clinical pregnancy rate (50.2% versus 47.0%, P = 0.688), miscarriage rate (9.8% versus 14.5%, P = 0.115) and live birth rate (45.0% versus 39.6%, P = 0.331) between the P4mNC-FET and HRT-FET groups after covariate adjustments. CONCLUSIONS: There were no differences in the clinical outcomes between the P4mNC-FET and HRT-FET cycles. These results indicate that P4mNC-FET cycles produce clinical outcomes comparable to those of more traditional HRT-FET while allowing greater flexibility in the timing of embryo transfer.

Development of an IVF prediction model for donor oocytes: a retrospective analysis of 10 877 embryo transfers.

STUDY QUESTION: Can we develop a prediction model for the chance of a live birth following the transfer of an embryo created using donated oocytes? SUMMARY ANSWER: Three primary models that included patient, past treatment, and cycle characteristics were developed using Australian data to predict the chance of a live birth following the transfer of an embryo created using donated oocytes; these models were well-calibrated to the population studied, achieved reasonable predictive power and generalizability when tested on New Zealand data. WHAT IS KNOWN ALREADY: Nearly 9% of ART embryo transfer cycles performed globally use embryos created using donated oocytes. This percentage rises to one-quarter and one-half in same-sex couples and women aged over 45 years, respectively. STUDY DESIGN, SIZE, DURATION: This study uses population-based Australian clinical registry data comprising 9384 embryo transfer cycles that occurred between 2015 and 2021 for model development, with an external validation cohort of 1493 New Zealand embryo transfer cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three prediction models were compared that incorporated patient characteristics, but differed in whether they considered use of prior autologous treatment factors and current treatment parameters. We internally validated the models on Australian data using grouped cross-validation and reported several measures of model discrimination and calibration. Variable importance was measured through calculating the change in predictive performance that resulted from variable permutation. The best-performing model was externally validated on data from New Zealand. MAIN RESULTS AND THE ROLE OF CHANCE: The best-performing model had an internal validation AUC-ROC of 0.60 and Brier score of 0.20, and external validation AUC-ROC of 0.61 and Brier score of 0.23. While these results indicate ∼15% less discriminatory ability compared to models assessed on an autologous cohort from the same population the performance of the models was clearly statistically significantly better than random, demonstrated generalizability, and was well-calibrated to the population studied. The most important variables for predicting the chance of a live birth were the oocyte donor age, the number of prior oocyte recipient embryo transfer cycles, whether the transferred embryo was cleavage or blastocyst stage and oocyte recipient age. Of lesser importance were the oocyte-recipient parity, whether donor or partner sperm was used, the number of prior autologous embryo transfer cycles and the number of embryos transferred. LIMITATIONS, REASONS FOR CAUTION: The models had relatively weak discrimination suggesting further features need to be added to improve their predictive power. Variation in donor oocyte cohorts across countries due to differences such as whether anonymous and compensated donation are allowed may necessitate the models be recalibrated prior to application in non-Australian cohorts. WIDER IMPLICATIONS OF THE FINDINGS: These results confirm the well-established importance of oocyte age and ART treatment history as the key prognostic factors in predicting treatment outcomes. One of the developed models has been incorporated into a consumer-facing website (YourIVFSuccess.com.au/Estimator) to allow patients to obtain personalized estimates of their chance of success using donor oocytes. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Australian government as part of the Medical Research Future Fund (MRFF) Emerging Priorities and Consumer Driven Research initiative: EPCD000007. L.R. declares personal consulting fees from Abbott and Merck, lecture fees from Abbott, receipt of an educational grant from Merck, past presidency of the Fertility Society of Australia & New Zealand and World Endometriosis Society and being a minor shareholder in Monash IVF Group (ASX:MVF). G.M.C. declares receipt of Australian government grant funding for the research study and the development and maintenance of the YourIVFSuccess website. O.F., J.N., and A.P. report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Live birth from ovarian grafted tissue after pelvic radiation for rectal cancer.

Objective: To study the management of a woman who returned to conceive after high-dose radiation treatment, with documentation of uterine dosimetry, and the efficacy of ovarian tissue grafted into an irradiated pelvis. Design: Case report. Setting: Private and public In Vitro Fertilization units. Patient: A 26-year-old woman underwent radiation treatment for rectal cancer, with half of the uterus and the fundus being exposed to radiation doses of 50 and 25 Gy, respectively. We report the details of the uterine assessment, determining suitability of conception with her own uterus, pregnancy surveillance, and reproductive outcome. Interventions: In Vitro Fertilization stimulation grafted ovarian tissue to assist with pregnancy. Main Outcome Measures: Successful conception and live birth, pregnancy complications and management of high risk pregnancy. Results: The results of magnetic resonance imaging and pelvic ultrasound showed a small uterus with preserved junctional zone anatomy, and although the endometrium was initially thin after high-dose estrogen administration, endometrial thickness increased with time. Twelve grafted ovarian tissue stimulation cycles led to 4 embryo transfers, the last of which resulted in a live birth. She had 2 cervical cerclage procedures because of cervical shortening and delivered a 3.3-kg healthy female neonate at 38 weeks of gestation via lower-segment cesarean section. Conclusions: Successful pregnancy is possible from ovarian tissue grafted into an irradiated pelvis, with high-dose uterine exposure. Careful uterine assessment needs to be undertaken to determine suitability of conception attempt with a patient's own uterus, in consultation with the medical team. Further studies are needed to correlate imaging and biopsy findings with reproductive outcomes.

When to randomize patients in a randomized controlled trial?

The timing of randomization should be considered carefully in the context of each trial because it has implications for the particular research question answered. In most instances, randomization should be delayed until as close as practically possible to the moment of intervention. In some cases, early randomization may offer certain advantages, but trialists should balance these, including any administrative complexity or inconvenience, against the risk of avoidable protocol violations and avoidable drop out.

Assessing obstetric outcomes: A systematic review and meta-analysis comparing fresh, artificial, and natural thaw embryo transfer cycles.

BACKGROUND: The increasing utilisation of in vitro fertilisation (IVF) has prompted significant interest in determining the optimal endometrial environment to increase pregnancy rates and minimise the obstetric complications associated with various embryo transfer strategies. AIMS: To determine which cycle is associated with increased obstetric complications: fresh embryo transfer (FreshET), natural thaw (NatThawET) or artificial thaw (ArtThawET). Outcomes of interest included: hypertensive disorders of pregnancy (HDP), gestational diabetes (GD), pre-term birth (PTB), post-partum haemorrhage (PPH) and large for gestational age (LGA). MATERIALS AND METHODS: A comprehensive search of MEDLINE, EMBASE, CENTRAL, and PUBMED was conducted from 1947 to May 17, 2022. Two independent reviewers carried out the screening, and data extraction for the following comparisons: ArtThawET vs NatThawET, ArtThawET vs FreshET, and NatThawET vs FreshET. Meta-analysis was conducted using a fixed-effect Mantel-Haenszel model. The quality of the studies was assessed using GRADEpro. RESULTS: A total of 23 studies were included in this review. ArtThawET was associated with a significantly increased odds of HDP (odds ratio (OR) 1.76, confidence interval (CI) 1.66-1.86), PTB (OR 1.18, CI 1.13-1.23), PPH (OR 2.61, CI 2.3-2.97) and LGA (OR 1.11, CI 1.07-1.15), compared to NatThawET. ArtThawET was also associated with increased odds of HDP (OR 2.13, CI 1.89-2.4), PPH (OR 3.52, CI 3.06-4.04) and LGA (OR 2.12, CI 1.77-2.56), compared to FreshET. Furthermore, NatThawET demonstrated increased odds of HDP (OR 1.20, CI 1.11-1.29), PPH (OR 1.25, CI 1.14-1.38) and LGA (OR 1.85, CI 1.66-2.07) compared to FreshET. CONCLUSION: When clinically feasible, ArtThawET should be avoided as a first-line option for IVF to reduce the risk of obstetric complications. An adequately powered, multicentre randomised controlled trial is necessary to confirm these findings and investigate the underlying pathophysiology.

Posthumous conception in Australia - legal and ethical considerations.

Posthumous conception, the ability to conceive a child after the death of one partner, is increasingly prevalent due to advances in Artificial Reproduction Technology (ART). This paper considers the complexities surrounding the practice in Australia, focusing primarily on the ethical and legal dimensions. It observes that state-based regulations in Australia create disparities in accessibility: some states prohibit the procedure without the deceased's written consent, while others permit it based on guidelines or lack explicit prohibitions. Addressing the juxtaposition of Will Theory and Interest Theory, it emphasises the ongoing debate on whether rights, particularly reproductive autonomy, outlive a person's demise. Finally, the paper highlights an evident inconsistency in Australian legislation and promotes a uniform approach across states.

Providers' attitudes towards payment to egg donors: an international survey.

The research question 'How do fertility professionals worldwide perceive the issue of payment for egg donation and does this view change under different circumstances?' was addressed. A worldwide online survey was conducted between January and March 2023, focusing on the views of fertility providers concerning egg donor payments. From the 3,790 IVF-Worldwide.com members invited, 532 (14%) from 88 countries responded. The majority of participants, primarily from Europe (38.9%) and Asia (20.1%), were fertility specialists, embryologists, and fertility nurses. Most (60.3%) favoured regulated donor compensation, with only 13% advocating for unrestricted amounts. Compensation opposition (22.4%) was often rooted in concerns about donors' best interests. When considering egg donation from low-resource to high-resource countries, 38.5% were opposed. When asked about compensating women who underwent elective, non-medical egg freezing should they choose to donate their unused oocytes, most responders supported it to some degree, with only 28.4% opposing any compensation. The survey revealed that a significant majority of fertility professionals worldwide are supportive of some form of compensation for egg donors. However, perspectives diverge depending on the specific scenario and the country of practice.

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.

Live birth rates in day 5 fresh versus vitrified single blastocyst transfer cycles: A cross-sectional analysis.

Background: The use of frozen embryo transfers (FET) in assisted reproduction has increased worldwide. Controlled ovarian hyperstimulation in a fresh transfer may impair endometrial-embryo synchronicity. However, there is conflicting evidence on live birth rates (LBR) and clinical pregnancy rates (CPR). Objective: To compare LBRs and CPRs between single autologous day 5 fresh vs. vitrified blastocyst transfer cycles, to investigate the impact of controlled ovarian hyperstimulation on embryo-endometrium asynchrony. Materials and Methods: A large cross-sectional analysis of 6002 embryo transfers (ET) comprised 3774 fresh and 2228 FET cycles from 2016 to 2019. Multivariate and subgroup analysis were performed for high responders ( > 20 oocytes). Results: Univariate analysis showed no difference in LBR (28.3% vs. 27.4%, p = 0.43) and CPR (32.2% vs. 30.9%, p = 0.30); however, multivariate analysis demonstrated significantly lower LBR (OR 0.864, p = 0.046, 95% CI 0.749-0.997) and CPR (OR 0.852, p = 0.024, 95% CI 0.742-0.979) in FET compared to fresh ETs. Younger participant age, previous in vitro fertilization pregnancy, advanced blastocyst expansion, higher trophectoderm quality, and lower cumulative number of ETs all improved the odds of LBR and CPR. Conventional in vitro fertilization, rather than intracytoplasmic sperm injection, improved CPR but not LBR. Body mass index affected neither LBR nor CPR. In the subgroup, multivariate analysis of high responders showed no difference in LBR or CPR. Conclusion: This study demonstrates relatively higher LBR and CPR of nearly 14% for fresh ETs compared to FETs, in multivariate analysis. A universal freeze-all strategy, without appropriate indication, may lead to suboptimal outcomes. In high responders, freeze-all cycles may be beneficial, as outcomes appear similar.

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.

Barriers to reproductive treatments in Australia.

BACKGROUND: Most couples in Australia want to have children but some might not attain their reproductive goals, experiencing involuntary childlessness or not reaching their desired family size. There is increased focus on helping couples achieve their reproductive goals. Identifying existing barriers, such as those related to social and societal factors, access to treatment and treatment success, is crucial to optimising outcomes. OBJECTIVE: This article discusses existing barriers to reproduction to help general practitioners (GPs) raise the topic of future fertility with patients, care for those presenting with fertility concerns and support those undergoing fertility treatment. DISCUSSION: Recognition of the impact of barriers such as age to achieving reproductive goals remains the highest priority for GPs. This will help them to broach this topic with patients, carry out a timely evaluation or provide referral, as well as discuss opportunities such as elective egg freezing. Other barriers can be mitigated by educating patients, informing them about available resources and supporting those undergoing fertility treatment as part of a multidisciplinary reproductive team.

How do IVF patients interpret claims about fertility treatments? A randomised survey experiment.

Trials evaluating the efficacy of IVF and various treatment options often focus on upstream outcome measures, improvements which may not translate into clinical outcome improvements. A cross-sectional online survey was distributed globally among IVF patients. Respondents were randomised to view one of 16 statements about a hypothetical IVF treatment option called 'FertiSure', stated to improve one of four upstream outcomes. Statements varied in whether they contained information stating that FertiSure was not proven to improve live-birth rates and about potential risks. Many patients inferred that improvements in upstream outcomes would result in improvements in the probability of live-birth. Nearly 80% of respondents were willing to use FertiSure. Respondents told that FertiSure was not proven to improve live-birth rates and were less willing to use FertiSure. More respondents agreed that FertiSure may pose a risk to patients when they were told this was the case. However, this did not affect their willingness to use FertiSure. Interestingly, 34% of respondents believed FertiSure would not improve the probability of live-birth but were still willing to use it. These results have implications for IVF clinic websites and information about treatment options which may not routinely contain statements about the limited evidence-base and possible risks.

Elective egg freezing: State of the ART.

BACKGROUND: Women are having children later in life, and the risk and prevalence of involuntary childlessness is thus increasing. Oocyte storage is widely available and increasingly used for elective (non-medical) indications by women trying to safeguard future fertility. There is controversy, however, regarding who should consider oocyte freezing, at what age and how many oocytes should be frozen. OBJECTIVE: The aim of this article is to provide an update on the practical management of non-medical oocyte freezing, including patient counselling and selection. DISCUSSION: The latest studies indicate that younger women are less likely to return to use their frozen oocytes, while a live birth is far less likely to result from oocytes frozen at an older age. While not guaranteeing a future pregnancy, oocyte cryopreservation is also associated with a substantial financial burden and uncommon but serious complications. Therefore, patient selection, appropriate counselling and maintenance of realistic expectations are crucial for this new technology to be used with the greatest positive impact.

Novel embryo selection strategies-finding the right balance.

The use of novel technologies in the selection of embryos during in vitro fertilisation (IVF) has the potential to improve the chances of pregnancy and birth of a healthy child. However, it is important to be aware of the potential risks and unintended consequences that may arise from the premature implementation of these technologies. This article discusses the ethical considerations surrounding the use of novel embryo selection technologies in IVF, including the growing uptake of genetic testing and others, and argues that prioritising embryos for transfer using these technologies is acceptable, but discarding embryos based on unproven advances is not. Several historical examples are provided, which demonstrate possible harms, where the overall chance of pregnancy may have been reduced, and some patients may have missed out on biological parenthood altogether. We emphasise the need for caution and a balanced approach to ensure that the benefits of these technologies outweigh any potential harm. We also highlight the primacy of patients' autonomy in reproductive decision-making, especially when information gained by utilising novel technologies is imprecise.