Narrow Results

Background: Louise Brown’s delivery in 1978 was the mark of a successful IVF program that has now been in practice for more than 40 years. The technology has delivered more than 8 million babies. Many breakthrough innovations were established to answer the problem in ART services. Optimizing ART biomarkers and cross border reproductive care have become a rising issue in ART services. Disruptive innovation disrupts the existing condition and takes the lead in the new market, including to change our patient behavior in health services. National health services addressed new issues about the impact of 4.0 industrial revolution on health workforce and our daily practices. Every disruptive innovation today is enhanced by a combination of physical, digital, and biological domain. The advancement in the area of the internet of things, artificial intelligence, virtual reality, nanotechnology, cloud computing, big data, deep learning, machine learning, robotics, and gene editing could potentially support us to innovate. And to improve the quality and outcome of ART, the introduction of the latest technology, such as robotics and artificial intelligence, has become an essential approach. A recent study discovered that the use of artificial intelligence would remove the embryologist’s subjectivity and improve the way we choose the best embryo for implantation. The next challenging issue in ART is improving the success rate through optimizing noninvasive biomarkers development. Many biological products such as blood, tissue, organ fluid can be assessed and considered to be used as IVF biomarkers. Proteomic tools were used and are needed to analyze a sample from subjects before it was created as a biomarker for improving the IVF services quality.

Conclusion: The development of IVF over 40 years has brought about many distinct achievements in the laboratory and in clinic. Industrial revolution 4.0 has generated many innovations that have helped improve the quality of ART services, including AUGMENT social egg freezing, artificial intelligence, and genome editing. In this era, precision medicine looks very promising for bridging the gap and increasing the accuracy and efficacy of promotive, preventive, diagnostic, and treatment approaches in reproductive medicine.

Long-term health outcomes after ART have largely focused on offspring health and perinatal parameters. Longer-term health outcomes in female patients remain difficult to fully assess. Hypothetical concerns about the effects of endocrine manipulation on hormone-sensitive conditions, e.g. breast disease, are confounded by variable factors in patients and treatments. Obstetric and perinatal factors endow an additional layer of complexity to the overall analysis and more research is required to appreciate all aspects of ART. Notwithstanding the knowledge gap, clinicians must endeavour to individualise management plans, taking into account the pros and cons of ART in the context of immediate, maternity-related and long-term health risks for their patients.

This review of recent literature examines current ART practice in terms of female health and disease as we strive for best practice in an ever-changing clinical and demographic fertility landscape.

The intravenous fat emulsion, intralipid, has been hypothesised to be an effective and safe treatment for repeated in vitro fertilisation (IVF), implantation failure and pregnancy loss. This exploratory, retrospective cohort study determined pregnancy outcomes and documented adverse events associated with intralipid use. Ninety-three women were identified as having received intralipid for a history of repeated unsuccessful IVF cycles and pre-viable pregnancy loss in two Australian IVF units that independently recruited between October 2014 and July 2016. Pregnancy outcomes and adverse events were recorded in fresh and frozen embryo transfer cycles in which the infusion was administered. The 93 women who received intralipid had a clinical pregnancy rate of 40.0%, compared with 35.0% in 651 age-matched controls undergoing IVF, which was not significantly different. The intralipid group had a livebirth rate of 35.7%. Apart from flushing, which was experienced by one individual, there were no adverse events associated with intralipid use. As a prelude to definitive evidence of benefit, we did not identify a safety concern or reduced pregnancy rates in intralipid users compared to controls. Indeed, these outcomes were better than expected in a poor prognosis group. This data supports an argument for large, randomised controlled trials to determine the benefit of intralipid in the treatment of recurrent implantation failure or miscarriage.

Background: Polycystic ovarian syndrome (PCOS) is a common cause of infertility in women. In-vitro fertilization (IVF) is required in 20–30% of women with PCOS trying to conceive. This is associated with increased risk of multiple gestation and ovarian hyperstimulation syndrome. Improvements in IVF techniques, safety standards, and the increased use of frozen embryos in recent years have lead to improved outcomes for women with PCOS. We performed a systematic review and meta-analysis to compare these outcomes with women without PCOS.

Search Methods: A search of PubMed, EMBASE, the Cochrane Central Register of clinical trials, and Scopus databases for all articles published until November 16th, 2017 identified 21 studies comparing IVF outcomes in PCOS and non-PCOS women. Inclusion criteria were Rotterdam criteria PCOS, comparable IVF regimes, immediate IVF outcomes, and pregnancy outcomes. Studies were excluded if the control group included any PCOS criteria, donor oocytes, or in-vitro maturation.

Outcomes: No difference was observed in live birth rate per cycle in women with vs. without PCOS (RR $=$ 1.01 [0.89, 1.16]; ${\text{I}}^{\mathrm{\text{2}}}=$ 82%), but the live birth rate per first cycle in PCOS cycles (RR $=$ 0.93 [0.88, 0.99]) was slightly lower. There was also no difference in the clinical pregnancy rate (RR 1.02 [0.89, 1.17]) or biochemical pregnancy rate (RR 1.03 [0.99, 1.08]) observed between the two groups. PCOS was associated with a significantly higher number of oocytes retrieved (mean difference $=$ 3.6; 95% CI [2.8, 4.4]), risk of miscarriage (RR 2.90 [2.09, 4.02]), and risk of ovarian hyperstimulation syndrome (RR 3.42 [2.28, 5.13]) per cycle.

Conclusion: Despite a widespread perception of poor reproductive potential, women with PCOS experience IVF outcomes similar to those without PCOS. Although there is a slightly lower live birth rate during their first stimulation cycle, success rates are similar after multiple cycles. PCOS is associated with a higher risk of ovarian hyperstimulation syndrome. Further studies are required to mitigate this risk.

Background: Treating patients with a history of poor ovarian response (POR) presents many challenges for the clinician. Poor in vitro fertilization (IVF) outcomes are a common end result. The aim of this article is to provide a detailed description of an ultralong estrogen priming (ULEP) cycle in the treatment of patients with a history of POR and to compare the outcomes to matched controls which were treated with other IVF protocols.

Methods: In a retrospective study, 50 patients who meet the Bologna criteria for POR were treated with 50 ULEP cycles. The results of these cycles were compared to 50 matched controls, who were treated with other IVF protocols.

Results: Patients who underwent the ULEP cycles required 3.2 more days of controlled ovarian hyperstimulation (COH) and required an extra 579 IU of follicle-stimulating hormone (FSH). The ongoing pregnancy rates per transfer were significantly greater in the ULEP group (35.1% vs. 9.1%, OR 5.4, 95% CI 1.4-21.2, p = 0.005) and per cycle started (26% vs. 6%, OR 5.5, 95% CI 1.5-20.8, p = 0.003).

Conclusions: Even though the ULEP cycle is long and demanding for the patients, the outcomes suggest that this treatment regime offers a viable alternative in patients with a history of POR.

Purpose: To study effect of paternal age on pregnancy outcomes of intracytoplasmic sperm injections (ICSI).

Methods: The present study is a retrospective analysis of 153 ICSI cycles on donor oocytes. The effect of paternal age on fertilization rates, implantation rates, total pregnancy rates, number of miscarriages and live births were analyzed.

Results: 1422 donor oocytes were injected with sperm from 153 men. Linear regression analysis revealed no association between paternal age (28-54 years) and fertilization rate. No association was found between the embryo quality and paternal age. Of the 359 embryos transferred, linear regression analysis revealed no association between paternal age and implantation rate. After correcting for maternal age, binary logistic regression analysis revealed no association between total pregnancy rates (B = 0.943, CI 0.861-1.033, P = 0.205), live birth rates (B = 1.018, CI 0.896-1.158, P = 0.562) and miscarriage rates (B = 0.944, CI 0.866-1.029, P = 0.193) and paternal age.

Conclusion: Paternal age does not seem to influence outcomes in assisted reproduction.

With continued improvements in blastocyst culture, cell sampling approaches, and genetic analysis platforms, the resulting improvements in embryo development and the resolution and accuracy of chromosome analysis have provided valuable insights into the preimplantation embryo. This includes the impact of in vitro culture conditions on chromosomal dynamics. Specifically, through analysis of embryo aneuploidy and mosaicism, a growing number of reports indicate that rates of chromosomal abnormalities can vary between IVF centers. Because differences in mosaicism reflect mitotic errors, this endpoint analysis suggests that IVF laboratory-controlled variables during embryo development may be influencing chromosome separation and segregation. A growing body of literature suggests that culture media may be one variable influencing preimplantation embryo aneuploidy and mosaicism. However, these data are far from definitive in demonstrating cause-and-effect. Whether reported differences may be due to media formulation, use of sequential media or single-step media, or uninterrupted culture approaches is unknown. Importantly, variables directly impacting media performance and embryo development, including pH, temperature, osmolality, and oxygen concentration, must also be considered and make it difficult to isolate the impact of culture media as the sole factor responsible. These IVF laboratory variables will be reviewed and literature suggesting a possible link to mitotic aneuploidy/mosaicism will be discussed.

Background and Objectives: The role of Anti Mullerian Hormone (AMH) in determining the outcome of in vitro fertilization (IVF) in endometriosis has been controversial. This study was conducted to assess whether AMH can predict poor response in endometriosis patients undergoing IVF and to compare the IVF outcomes among the different stages of endometriosis.

Methodology: A retrospective study was conducted among 90 endometriosis patients undergoing IVF using the flexible antagonist protocol from January 2016 to December 2018 at DY Patil Medical College, Navi Mumbai. Serum AMH levels were obtained from different patients, primary outcome being clinical pregnancy rate (CPR) while the secondary outcome included the number of oocytes retrieved, number of mature oocytes obtained, fertilization rates (FR), and number of good quality embryos formed. Data was analyzed with SPSS 16.0. Mann-Whitney U and chi-square tests were used to compare the outcomes of IVF with AMH level in different stages of endometriosis. Receiver Operator Characteristic (ROC) curves were plotted to know the predictive ability of AMH by determining the area under the curve (AUC), P value < 0.05 was considered significant for all statistical tests.

Results: AUC was found to be significant for AMH in detecting poor response among those with late staged endometriosis but with poor accuracy (AUC = 0.65, P = 0.02^∗). Considering a median AMH level of 1.24 ng/mL with sensitivity and specificity of > 60%, the primary and secondary outcomes were significantly higher among those with median AMH levels of more than 1.24 ng/mL compared to those with the median ≤ 1.24 ng/mL. The significance, however, was mainly found in the late stages of endometriosis (P < 0.05). Fertilization rates, good quality embryos, and CPR did not vary with AMH levels among those with early stages of endometriosis (P > 0.05). The outcomes of IVF did not vary significantly across the different stages of endometriosis except for good quality embryos which were formed in patients with early staged endometriosis (P < 0.05).

Conclusion: AMH levels may be a predictor of nonconception with poor accuracy in late stages of endometriosis (III/IV), while good quality embryos were obtained in patients with early stages of endometriosis.

Aim: The study evaluated the effect of body mass index (BMI) and age on in vitro fertilization (IVF) outcomes in women with polycystic ovary syndrome (PCOS).

Methods: A retrospective study of 412 IVF cycles in PCOS patients aged between 20 and 40 years from January 2019 to 2022. Patients were divided into three groups based on their BMI-normal (18.5–24.9kg/m²), overweight (25–29.9kg/m²), and obese ($\ge 30$kg/m²). The patients were divided into two groups based on their age $<35$ and $\ge 35$ years. The IVF cycle outcomes, clinical pregnancy (CPR), and live birth rates (LBR) were studied. The Mantel–Haenszel Chi-square test was used for statistics.

Results: The oocyte yield and endometrial thickness, fertilization, CPR, and LBR were significantly higher in the normal BMI group. Similarly, oocyte yield, mature oocytes, and endometrial thickness were significantly higher in the younger age-group. Comparing the CPR in younger and older normal, overweight, and obese groups, it was observed to be highest in the younger, normal BMI group and lowest in the older, obese group. The LBR were significantly higher in the younger, normal-BMI group compared to the older, obese patients.

Conclusion: Oocyte yield, CPR, and LBR were higher in the normal-BMI PCOS patients. The oocyte yield, endometrial thickness, and fertilization rates were higher in the younger age group. The CPR and LBR were significantly lower in the older obese patients. Patients with PCOS must be encouraged to normalize BMI before embarking on IVF. Timely treatment must be encouraged for better IVF outcomes.

Background: Ovarian endometriomas have been shown to have a negative effect on fertility. There is a dilemma on the timing for surgery either before or after the fertility treatment. By delaying surgical treatment for infertile patients with endometriomas, medical treatment has become an important choice for these patients. The objectives of this review were to compare the efficacy of medical treatment on endometrioma size and endometriosis-associated pelvic pain (EAPP).

Methods: We performed a systematic review and meta-analysis examining women who have endometrioma and underwent medical therapy for endometrioma size reduction. The primary outcome measure was endometrioma size reduction. Secondary outcome measures EAPP.

Results: We included 14 studies for the meta-analysis. We performed a systematic review and meta-analysis examining women with endometrioma who underwent medical therapy for endometrioma size reduction. The primary outcome measure was endometrioma size reduction. Secondary outcome measure is EAPP. The majority of the studies were non-randomized controlled trials (RCTs; 9/14), and five were RCTs. Women who received medical treatment have a significant endometrioma size reduction in diameter compared to women not receiving any medical treatment or placebo (MD −9.66mm; 95% CI [−13.85, −5.46], three studies, 467 women, $I^2=96$%) and a reduction in visual analog scale (VAS) for EAPP (MD −2.64; 95% CI [−3.31, −1.97], two studies, 338 women, $I^2=0$%). Women who received dienogest (DNG) treatment have a significant endometrioma size reduction in diameter (MD −4.61mm; 95% CI [−9.08, −0.15], three studies, 220 women, $I^2=96$%). Compared to women receiving other medical treatments, women receiving DNG treatment had more VAS reduction of EAPP (MD −0.46; 95% CI [−0.62, −0.31], four studies, 451 women, $I^2=85$%).

Conclusions: The use of medical therapy is associated with endometrioma size reduction and a reduction in endometriosis-related pain when compared with no medical treatment given. With the availability of various medical options, surgery can thus be avoided to minimize the risk of damage to the ovarian reserves.