Obstetrics and Gynaecology - Research Publications
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ItemApplying plastic surgery principles to ovarian tissue transplantation(AME PUBLISHING COMPANY, 2021-07)Ovarian tissue cryopreservation (OTC) and transplantation is an innovative procedure increasingly utilized to help preserve fertility after gonadotoxic treatments especially in cancer patients. Approximately 30% of autotransplanted patients are able to achieve live birth, typically with the help of in-vitro fertilization. Numerous techniques and grafting sites have been described to continue to increase this figure. In the field of plastic surgery, tissue grafting has been successful performed for thousands of years and knowledge in this area has been significantly refined. A qualitative review of the literature using PubMed, Cochrane, SCOPUS and Medline databases was performed to look for articles relating to ovarian tissue transplantation (OTT) and comparisons made to plastic surgery tissue grafting. Many parallels were found between the principles of grafting in plastic surgery and the principles of OTT, including pre-operative patient optimization, suitable donor site selection, tissue harvest and preparation, graft site choice, immobilization of the graft and post-operative care. Consideration of the benefits and risks of using orthotopic versus heterotopic recipient sites is also highly important with regards to graft take, morbidity and ease of access of oocyte collection. We believe that ongoing discussion between disciplines can have the potential to improve knowledge, surgical techniques and patient outcomes.
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ItemUse of intracytoplasmic sperm injection (ICSI) in normospermic men may result in lower clinical pregnancy and live birth rates(WILEY, 2019-10)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.
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ItemComparing pregnancy outcomes between natural cycles and artificial cycles following frozen-thaw embryo transfers(Wiley, 2020-10)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.
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ItemIs it possible to apply trial outcomes to a real-world population? A novel approach to External Validity Analysis(WILEY, 2020-04)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.
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ItemA double-blinded, randomized, placebo-controlled trial assessing the effects of nifedipine on embryo transfer: Study protocol(LIPPINCOTT WILLIAMS & WILKINS, 2017-12)INTRODUCTION: Implantation failure is the main factor affecting the success rate of in vitro fertilization (IVF) procedures. Studies have reported that uterine contractions (UCs) at the time of embryo transfer (ET) were inversely related to implantation and pregnancy rate, hence reducing the success of IVF treatment. Various pharmacological agents, with the exception of calcium channel blocker (CCB), have been investigated to reduce UC. In this regard, we are presenting a proposal for a double-blind randomized placebo-controlled trial. The trial aims to determine whether nifedipine, a CCB with potent smooth muscle relaxing activity and an excellent safety profile, can improve the outcome of ET. METHODS AND ANALYSES: We will recruit 100 infertile women into one of 2 groups: placebo (n = 50) and nifedipine 20 mg (n = 50). Study participants will be admitted 30 minutes prior to ET and given either tablet after their baseline vital signs have been recorded. They will then undergo ET and be observed for adverse events for another 30 minutes post-ET. The primary outcome will be implantation rate and clinical pregnancy rate. Secondary outcomes include adverse events, miscarriage and pregnancy, and neonatal outcomes. Resulting data will then be analyzed using t test, Chi-square test, and multivariate test to compare outcomes between the 2 groups for any statistical significance. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines.