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17 pages, 386 KiB  
Article
Growth Hormone Therapy in Recurrent Implantation Failure: Stratification by FSH Receptor Polymorphism (Asn680Ser) Reveals Genotype-Specific Benefits
by Mihai Surcel, Georgiana Nemeti, Iulian Gabriel Goidescu, Romeo Micu, Cristina Zlatescu-Marton, Ariana Anamaria Cordos, Gabriela Caracostea, Ioana Cristina Rotar, Daniel Muresan and Dan Boitor-Borza
Int. J. Mol. Sci. 2025, 26(15), 7367; https://doi.org/10.3390/ijms26157367 - 30 Jul 2025
Viewed by 185
Abstract
Recurrent implantation failure (RIF) remains a challenging clinical problem. Growth hormone (GH) co-treatment has been explored as an adjunct in poor responders and RIF patients, with inconsistent evidence of benefit. This prospective cohort study assessed the impact of GH supplementation in 91 RIF [...] Read more.
Recurrent implantation failure (RIF) remains a challenging clinical problem. Growth hormone (GH) co-treatment has been explored as an adjunct in poor responders and RIF patients, with inconsistent evidence of benefit. This prospective cohort study assessed the impact of GH supplementation in 91 RIF patients undergoing in vitro fertilization, stratified by FSHR (follicular stimulating hormone receptor) genotype Asn680Ser with or without GH supplementation. Patients were stratified by FSHR genotype into homozygous Ser/Ser versus Ser/Asn or Asn/Asn groups. Overall, GH co-treatment conferred modest benefits in the unselected RIF cohort, limited to a higher cumulative live birth rate compared to controls and elevated leukemia inhibitory factor (LIF) levels (p < 0.05 both). When stratified by FSHR genotype, the Ser/Ser subgroup exhibited markedly better outcomes with GH. These patients showed a higher (0.5 vs. 0.33, p = 0.003), produced more embryos (2.88 vs. 1.53, p = 0.02), and had a markedly improved cumulative live birth rate—50% with GH versus 13% without—highlighting a clinically meaningful benefit of GH in the Ser/Ser subgroup. No significant benefit was observed in Asn allele carriers. These findings suggest that FSHR genotyping may help optimize treatment selection in RIF patients by identifying those most likely to benefit from GH supplementation. Full article
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14 pages, 787 KiB  
Article
Preimplantation Genetic Testing for Aneuploidy Versus Morphological Selection in Women Aged 35–42: Results of a Pilot Randomized Controlled Trial
by Yusuf Beebeejaun, Daniela Bakalova, Anastasia Mania, Timothy Copeland, Ippokratis Sarris, Kypros Nicolaides, Antonio Capalbo and Sesh K. Sunkara
J. Clin. Med. 2025, 14(14), 5166; https://doi.org/10.3390/jcm14145166 - 21 Jul 2025
Viewed by 516
Abstract
Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women [...] Read more.
Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)
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18 pages, 5349 KiB  
Article
Qatar’s National Expanded Metabolic Newborn Screening Program: Incidence and Outcomes
by Tala Jamaleddin, Karen El-Akouri, Sumaya Abiib, Rola Mitri, Mamatha Ramaswamy, Sara Musa, Rehab Ali, Noora Shahbeck, Hilal Al Rifai, Ghassan Abdoh, Tawfeg Ben-Omran, Osama Y. Al-Dirbashi and Mashael Al-Shafai
Int. J. Neonatal Screen. 2025, 11(3), 50; https://doi.org/10.3390/ijns11030050 - 30 Jun 2025
Viewed by 667
Abstract
Background: Newborn screening is an essential public health strategy that aims to detect a range of conditions, including inborn errors of metabolism, in neonates shortly after birth. The timely identification is crucial due to the asymptomatic nature of many conditions at birth, but [...] Read more.
Background: Newborn screening is an essential public health strategy that aims to detect a range of conditions, including inborn errors of metabolism, in neonates shortly after birth. The timely identification is crucial due to the asymptomatic nature of many conditions at birth, but which can lead to significant health complications if left untreated. Through this study, we aimed to investigate the incidence of IEMs screened by the Qatar National Newborn Screening Program. Methods: We retrospectively analyzed a total of 351,223 newborns screened from 2010 to 2023. The incidence for the studied IEMs was calculated and correlated with demographics, consanguinity, and family history. In addition, the diagnostic yield of different tests utilized was assessed. Results: Our study revealed a total of 318 positive cases with IEMs, and a significantly high incidence of 1:1105 for IEMs in Qatar. Classical Homocystinuria was the most frequently detected condition, with a cumulative incidence of 1:6754 live births, linked to the founder variant p. Arg336Cys in the CBS gene. Aminoacidopathies were the most prevalent category, followed by fatty acid oxidation disorders, organic acidurias, biotinidase deficiency, and urea cycle disorders. Genetic testing showed a high diagnostic yield of 90%. Of the 60 cases that underwent targeted variant testing, 98% were confirmed, while 90% of the 59 cases tested by single gene testing were confirmed. Conclusions: Our study provides the incidence rates of IEMs in Qatar and novel insights that could facilitate setting up/developing IEM incidence-reducing strategies and improving outcomes for affected newborns and their families. Full article
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12 pages, 648 KiB  
Article
DuoStim Shows Comparable Efficacy but Better Efficiency than Two Conventional Stimulations in Poor/Suboptimal Responders Undergoing Vitrified Oocyte Accumulation for PGT-A
by Stefano Canosa, Alberto Revelli, Danilo Cimadomo, Alberto Vaiarelli, Gianluca Gennarelli, Daniela Guidetti, Andrea Roberto Carosso, Laura Rienzi, Filippo Maria Ubaldi and Francesca Bongioanni
Life 2025, 15(6), 899; https://doi.org/10.3390/life15060899 - 31 May 2025
Viewed by 901
Abstract
This study compared the DuoStim protocol with two conventional follicular phase stimulations for vitrified oocyte accumulation in poor-prognosis patients undergoing PGT-A. A retrospective analysis of 112 IVF cycles was conducted, with 66 cycles among patients undergoing DuoStim (DS-Group) and 46 among patients undergoing [...] Read more.
This study compared the DuoStim protocol with two conventional follicular phase stimulations for vitrified oocyte accumulation in poor-prognosis patients undergoing PGT-A. A retrospective analysis of 112 IVF cycles was conducted, with 66 cycles among patients undergoing DuoStim (DS-Group) and 46 among patients undergoing conventional follicular phase stimulations (DF-Group). The primary outcome was the time to live birth, while secondary outcomes included clinical pregnancy rate, miscarriage rate, live birth rate, and cumulative live birth rate. The final analysis included 66 patients in the DS-Group and 40 in the DF-Group, as 6 women (13%) in the DF-Group discontinued treatment after the first stimulation. Oocyte yield was similar between groups (8.4 ± 3.9 in DS-Group vs. 8.2 ± 4.0 in DF-Group, p = 0.80), as was the number of euploid blastocysts (0.9 ± 1.2 vs. 1.1 ± 1.1, p = 0.37). The cumulative live birth rate was 22.7% in the DS-Group and 25% in the DF-Group (multivariate odds ratio adjusted for maternal age and male factor: 1.05, p = 0.93). The time to live birth was significantly shorter in the DS-Group (81.5 ± 15.5 days) compared to the DF-Group (153.7 ± 78.2 days, p < 0.001). DuoStim showed similar efficacy but a shorter time to live birth. Full article
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40 pages, 11073 KiB  
Article
Bioinformatic Analysis of Complex In Vitro Fertilization Data and Predictive Model Design Based on Machine Learning: The Age Paradox in Reproductive Health
by Myrto A. Lantzi, Eleni Papakonstantinou and Dimitrios Vlachakis
Biology 2025, 14(5), 556; https://doi.org/10.3390/biology14050556 - 16 May 2025
Cited by 1 | Viewed by 801
Abstract
Since its inception in 1987, in vitro fertilization (IVF) has constituted a significant medical achievement in the field of fertility treatment, offering a viable solution to the challenge of infertility. The continuous evolution of assisted reproductive technology (ART) has brought its relationship with [...] Read more.
Since its inception in 1987, in vitro fertilization (IVF) has constituted a significant medical achievement in the field of fertility treatment, offering a viable solution to the challenge of infertility. The continuous evolution of assisted reproductive technology (ART) has brought its relationship with the rapidly developing field of artificial intelligence (AI), in particular with techniques such as machine learning (ML), a rapidly evolving area of specialization. In fact, it is responsible for significant developments in the field of precision medicine, as well as in preventive and predictive medicine. The analysis focuses on a large volume of clinical data and patient characteristics of those who underwent assisted reproduction treatments. Concurrently, the utilization of machine learning algorithms has facilitated the development and implementation of predictive models. The objective is to predict the success of treatments for external fertilization based on processed clinical data. This study encompasses statistical analysis techniques and artificial intelligence algorithms for the correlation of variables, such as patient characteristics, the history of pregnancies, and the clinical and embryological parameters. The analysis and creation of prognostic models were compared with the objective of identifying factors that influence the outcome of IVF treatments. The potential for implementing a predictive model in routine clinical practice was also investigated. The findings revealed trends and factors that warrant attention. Such findings may prompt questions regarding the impact of the patient’s age on treatment efficacy. Moreover, the value of developing a predictive model based entirely on patient data prior to the commencement of treatment was also investigated. This approach to the processing and utilization of clinical data demonstrates the potential for optimization and documentation of therapeutic procedures. The objective is to reduce costs and the emotional burden while increasing the success rate of IVF treatments. Full article
(This article belongs to the Section Bioinformatics)
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15 pages, 914 KiB  
Article
A Comprehensive Comparison of PICSI and ICSI Techniques Through a Triple-Blinded Trial: Effects on Embryo Quality, Cumulative Pregnancy Rate, and Live Birth Rate
by Lucia Alegre, Laura Carrión-Sisternas, Lorena Bori, Irene Hervás, Jose Remohí, Nicolás Garrido and Marcos Meseguer
Biomedicines 2025, 13(5), 1104; https://doi.org/10.3390/biomedicines13051104 - 1 May 2025
Viewed by 1278
Abstract
Background: Sperm selection is critical in assisted reproduction, typically relying on swim-up and centrifugation density gradients. New methods, such as PICSI (physiological intracytoplasmic sperm selection), aim to enhance outcomes by selecting mature sperm based on hyaluronic acid (HA) binding and have generated [...] Read more.
Background: Sperm selection is critical in assisted reproduction, typically relying on swim-up and centrifugation density gradients. New methods, such as PICSI (physiological intracytoplasmic sperm selection), aim to enhance outcomes by selecting mature sperm based on hyaluronic acid (HA) binding and have generated interest due to their potential impact on the clinical outcomes of patients who undergo assisted reproductive treatments. Methods: A single-center, prospective, and triple-blinded study was conducted with 277 couples in the egg donation program. The oocytes of each recipient patient were randomly microinjected using the ICSI or PICSI technique and maintained in culture in time-lapse incubators until blastocyst formation. Biological and clinical outcomes were analyzed, including fertilization and blastocyst formation rates, embryo morphokinetics, pregnancy, miscarriage, and live birth rates, and artificial intelligence-assigned embryo quality scores. Results: Clinical outcomes were comparable between the two groups, but a higher pregnancy rate was observed in the PICSI group than in the ICSI group (74.04% vs. 70.87%). Although blastocyst formation rates were similar on both day 5 (D5) and day 6 of development, the proportion of good-quality embryos on D5 was higher in the PICSI group (68.27%) than in the ICSI group (63.47%) (p > 0.05). Finally, the cumulative pregnancy rate was significantly higher in the experimental group than in the control group (88% vs. 72%) after four embryo transfers (p < 0.05). Conclusions: Utilizing HA to perform sperm selection during ICSI procedures does not increase live birth rates. However, it may enhance the quality of the selected sperm. This could be beneficial for patients in egg donation programs, particularly for those who have experienced repeated pregnancy loss. Full article
(This article belongs to the Special Issue Molecular Regulation of Spermatozoa—Second Edition)
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10 pages, 1968 KiB  
Article
The Identification of Molecular Ploidy Status of Abnormal Pronuclear Zygotes Reveals a Significant Number of Euploid Blastocysts Available for Conception
by Blair R. McCallie, Mary E. Haywood, Lauren N. Henry, Rachel M. Lee, William B. Schoolcraft and Mandy G. Katz-Jaffe
Biomedicines 2025, 13(1), 51; https://doi.org/10.3390/biomedicines13010051 - 28 Dec 2024
Viewed by 1694
Abstract
Objective: Abnormally fertilized embryos are often discarded during in vitro fertilization due to the fact that known chromosomal ploidy abnormalities lead to implantation failure or pregnancy loss. The objective of this study was to determine if pronuclear numeration (PN) observed at fertilization check [...] Read more.
Objective: Abnormally fertilized embryos are often discarded during in vitro fertilization due to the fact that known chromosomal ploidy abnormalities lead to implantation failure or pregnancy loss. The objective of this study was to determine if pronuclear numeration (PN) observed at fertilization check is representative of the true ploidy status of the subsequent developing blastocyst in order to maximize the number of viable embryos available for infertility patients and increase their chances of conception. Methods: Upon successful fertilization, pronuclear numeration was noted, and zygotes were cultured to the blastocyst stage. Biopsied trophectoderm cells were then lysed, and the isolated DNA was whole-genome amplified followed by library preparation. Next-generation sequencing was performed for PGT-A, and excess whole-genome amplified DNA was utilized for single nucleotide polymorphism beadchip array analysis. Results: At the time of fertilization check on day 1 of embryo development, when there were no visible pronuclei (n = 291), 56% of these 0PN blastocysts were confirmed to be diploid and normally fertilized. The remaining 41.9% were aneuploid, and 2.1% of the 0PN blastocysts contained only 23 haploid chromosomes. Upon analysis of the 1PN blastocysts (n = 217), just over a third (36.4%) only contained 23 haploid chromosomes (23XO), with another third (31.8%) identified as aneuploid, and surprisingly, the remaining third (31.8%) confirmed to be diploid and normally fertilized. In contrast, 50% of the 3PN blastocysts (n = 172) showed the presence of a third set of 23 parental chromosomes and were confirmed to be triploid (69XXY = 59.3% and 69XXX = 40.7%), with 41.9% identified as aneuploid and, interestingly, a small percentage (8.1%) confirmed to be diploid with normal fertilization. A very small proportion of biopsied blastocysts (0.63%) displaying the correct number of pronuclei for normal fertilization (2PN) were also identified as triploid with a third set of 23 parental chromosomes. To date, there have been 74 euploid embryo transfers from zygotes originally identified with an alternate pronuclear numeration, resulting in 16 ongoing pregnancies and 32 healthy live births, rates that match those typically observed with normally fertilized 2PN zygotes (>60%). Conclusions: A surprising number of blastocysts that were identified to have alternate pronuclear numeration at fertilization check on day 1 of embryo development were actually determined to be diploid with normal fertilization after molecular analysis. Accurate identification of haploid and tripoid zygotes is critical to prevent implantation failure and pregnancy loss and allows for the identification of all euploid embryos in a cohort, which has the potential to increase cumulative live birth rates for infertility patients. Full article
(This article belongs to the Special Issue Molecular and Genetic Bases of Infertility)
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13 pages, 281 KiB  
Review
Ethanol Sclerotherapy for Endometriomas in Infertile Women: A Narrative Review
by Yavuz Emre Şükür, Batuhan Aslan, Bulut Varlı, Pınar Özcan, Angelos Daniilidis and Dimitrios Rafail Kalaitzopoulos
J. Clin. Med. 2024, 13(24), 7548; https://doi.org/10.3390/jcm13247548 - 11 Dec 2024
Cited by 1 | Viewed by 1836
Abstract
Ethanol sclerotherapy (EST) has gained attention as a minimally invasive treatment option for ovarian endometriomas, particularly in infertile women with endometrioma undergoing in vitro fertilization (IVF). Endometriomas are associated with decreased ovarian reserve and impaired fertility outcomes, and traditional surgical approaches, such as [...] Read more.
Ethanol sclerotherapy (EST) has gained attention as a minimally invasive treatment option for ovarian endometriomas, particularly in infertile women with endometrioma undergoing in vitro fertilization (IVF). Endometriomas are associated with decreased ovarian reserve and impaired fertility outcomes, and traditional surgical approaches, such as cystectomy, often lead to further reductions in ovarian reserve. Ethanol sclerotherapy offers a potential alternative that preserves ovarian function while effectively managing endometriomas. This review examines the safety, efficacy, and impact of EST on ovarian reserve, IVF outcomes, and recurrence rates. Comparative studies suggest that pregnancy rates following EST are similar to or better than those after cystectomy, with the added benefit of more oocytes retrieved, which may lead to higher cumulative live birth rates. Despite these promising results, challenges such as recurrence and complications, particularly with prolonged ethanol exposure, remain. The use of transvaginal versus laparoscopic approaches and optimal ethanol exposure protocols are areas of ongoing research. The need for further large-scale, prospective studies is highlighted to refine the EST protocol and better understand the long-term outcomes. Sclerotherapy presents a feasible option for preserving fertility in women with endometriomas, with positive implications for IVF success and ovarian reserve preservation. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Endometriosis)
10 pages, 910 KiB  
Article
Effect of Paternal Body Mass Index on Cumulative Live Birth Rates: Retrospective Analysis of 3048 Embryo Transfers in Couples Using Autologous Gametes
by Laura Mossetti, Irene Hervás-Herrero, María Gil-Juliá, Ana Navarro Gomez-Lechon, Rosa María Pacheco-Rendón, Rocío Rivera-Egea and Nicolás Garrido-Puchalt
Cells 2024, 13(22), 1836; https://doi.org/10.3390/cells13221836 - 6 Nov 2024
Viewed by 1159
Abstract
Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) [...] Read more.
Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) and clinical reproductive outcomes by evaluating the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbRs), and oocytes used (OUs) in consecutive treatments until achieving the first newborn. A retrospective study was performed, and Kaplan–Meier survival curves were created to observe CLBRs with regard to the paternal BMI, adjusted by relevant confounders through Cox regression models. The participants were couples undergoing intracytoplasmic sperm injection (ICSI) and ET in Spanish IVIRMA clinics using autologous gametes. The cohort was subdivided based on paternal BMI: normal (18.5–24.99 kg/m2) (N), overweight (25–29.99 kg/m2) (OV), or obese (≥30 kg/m2) (OB) patients. A total of 4750 ICSI cycles were included, encompassing 49,485 mature oocytes, 23,963 blastocysts, and 3048 ETs. When calculating CLBRs based on the number of ETs carried out until live birth was achieved, no statistically significant differences were found (p = 0.72). After adjusting for maternal age and BMI, female infertility diagnosis, the use of preimplantation genetic testing, and the number of ETs, Cox regression showed that there were no statistically significant differences between the BMI groups (HR: 0.94 [95% CI: 0.7–1.2]; p = 0.59). When calculating CLBRs considering EmbRs, there was a similarity between the BMI groups (p = 0.57). However, there were no statistically significant differences in the adjusted Cox regression (HR: 0.93 [95% CI: 0.7–1.2]; p = 0.51). Finally, when calculating CLBRs considering OUs, the results were comparable among BMI subgroups (p = 0.75), and there were no statistically significant differences with adjusted Cox regression (HR: 0.95 [95% CI: 0.8–1.2]; p = 0.66). In conclusion, paternal BMI was not associated with clinical reproductive outcomes when considering the ETs, EmbRs, or OUs needed to reach the first liveborn (LB). Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Reproductive System Diseases)
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11 pages, 245 KiB  
Article
Premature Progesterone Rise Is Associated with Higher Cumulative Live Birth Rate with Freeze-All Strategy
by Yu Wang, Ming-Jer Chen, Hwa-Fen Guu, Ya-Fang Chen, Hsiao-Fan Kung, Jui-Chun Chang, Li-Yu Chen, Shih-Ting Chuan and Yu-Chiao Yi
J. Clin. Med. 2024, 13(12), 3439; https://doi.org/10.3390/jcm13123439 - 12 Jun 2024
Cited by 1 | Viewed by 2009
Abstract
Background/Objectives: This paper undertakes an investigation into the implications of premature progesterone rise (PPR) on pregnancy outcomes in freeze-all strategy cycles. Methods: A retrospective cohort study encompassing 675 IVF/ICSI cycles using a freeze-all strategy was enrolled. The cycles were categorized into two groups [...] Read more.
Background/Objectives: This paper undertakes an investigation into the implications of premature progesterone rise (PPR) on pregnancy outcomes in freeze-all strategy cycles. Methods: A retrospective cohort study encompassing 675 IVF/ICSI cycles using a freeze-all strategy was enrolled. The cycles were categorized into two groups based on serum progesterone levels at the time of hCG administration: 526 cycles had levels below 1.5 ng/mL, while 149 cycles had levels equal to or above 1.5 ng/mL. Results: The findings revealed a significantly higher number of mature follicles and retrieved oocytes in patients with PPR across all AMH categories. Multiple analyses revealed factors influencing PPR, including the duration of induction and the number of retrieved oocytes. Within the same oocyte retrieval number group, patients with PPR demonstrated non-inferior pregnancy outcomes compared to non-PPR patients. Upon adjustment for age, AMH, and total follicle-stimulating hormone (FSH) dosage, PPR maintained a positive correlation with the cumulative live birth rate (LBR). Conclusions: The study showed that PPR correlates with an increase in retrieved oocytes while maintaining similar embryo quality and oocyte retrieval rates and results in a higher cumulative LBR. Full article
(This article belongs to the Section Obstetrics & Gynecology)
12 pages, 668 KiB  
Article
Time-Lapse Incubation for Embryo Culture-Morphokinetics and Environmental Stability May Not Be Enough: Results from a Pilot Randomized Controlled Trial
by Gilat C. Sacks, Henny Mozes, Ruth Ronn, Talia Elder-Geva, Oshrat Schonberger, Ido Ben-Ami and Naama Srebnik
J. Clin. Med. 2024, 13(6), 1701; https://doi.org/10.3390/jcm13061701 - 15 Mar 2024
Cited by 4 | Viewed by 2117
Abstract
Background: Does the Time-lapse Incubator (TLI) add value to reproductive outcomes when its two components, undisturbed culturing and morphokinetic embryo grading, are separated. Methods: A prospective pilot, randomized, controlled, double-blinded, single-center study was conducted during the years 2016–2020. In total, 102 patients were [...] Read more.
Background: Does the Time-lapse Incubator (TLI) add value to reproductive outcomes when its two components, undisturbed culturing and morphokinetic embryo grading, are separated. Methods: A prospective pilot, randomized, controlled, double-blinded, single-center study was conducted during the years 2016–2020. In total, 102 patients were randomized into three groups: (1) conventional incubation with morphological evaluation only (n = 34), (2) TLI with both morphological and morphokinetic evaluations (n = 32), and (3) TLI with morphological evaluation only (n = 36). All arms were cultured in ESCO-MIRI® incubators. A total of 1061 injected mature oocytes were evaluated (420 in arm 1, 285 in arm 2, and 356 in arm 3). The primary outcome was live birth rates. Secondary outcomes included clinical and cumulative pregnancy rates as well as embryo quality. Embryos in arm 3 were retrospectively evaluated for their morphokinetic score. Results: No significant difference was found in the live birth rate for single embryo transfer cycles (SET) (35% vs. 31.6% vs. 24%, p = 0.708) or double embryo transfer (DET) cycles (41.7% vs. 38.5% vs. 36.4%, p = 0.966). Comparable pregnancy rates, clinical pregnancy rates, and cumulative pregnancy were found for similar top-quality embryos for days 2, 3, and blastocyst stages across groups. A similar number of embryos were suitable for either transfer or cryopreservation within the different groups. For 62.8% of the embryos in arm 3, the morphokinetic and morphologic evaluations were similar. In only 2/36 (5.6%) treatment cycles, the use of morphokinetic scoring may have helped the patient avoid undergoing an additional treatment cycle. In the other cases, morphokinetic scoring would not have changed the end point of pregnancy. Conclusions: The two components of the TLI system—undisturbed culturing and morphokinetic embryo grading—do not appear to have a significant additional value in reproductive outcome, although these results should be validated by an RCT. Full article
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24 pages, 352 KiB  
Review
The Use of Non-Apoptotic Sperm Selected by Magnetic Activated Cell Sorting (MACS) to Enhance Reproductive Outcomes: What the Evidence Says
by Nicolás Garrido and María Gil Juliá
Biology 2024, 13(1), 30; https://doi.org/10.3390/biology13010030 - 4 Jan 2024
Cited by 7 | Viewed by 4345
Abstract
Sperm selection of the most competent sperm is a promising way to enhance reproductive outcomes. Apoptosis is the programmed cell death process to maintain tissue homeostasis, and MACS sperm selection of non-apoptotic cells enables the removal of apoptotic sperm from an ejaculate, thus [...] Read more.
Sperm selection of the most competent sperm is a promising way to enhance reproductive outcomes. Apoptosis is the programmed cell death process to maintain tissue homeostasis, and MACS sperm selection of non-apoptotic cells enables the removal of apoptotic sperm from an ejaculate, thus leaving the non-apoptotic available to be microinjected, but given the associated costs of adding these sperm selection steps to the routine practice, there is a need for a careful examination of the literature available to answer questions such as who can benefit from this MACS, how significant this improvement is, and how robust the evidence and data available supporting this choice are. Thus, the aim of this narrative review was to objectively evaluate the available evidence regarding the potential benefits of the use of MACS. From the literature, there are controversial results since its implementation as an in vitro fertilization add-on, and this may be explained in part by the low quality of the evidence available, wrong designs, or even inadequate statistical analyses. We concluded that the benefits of adding MACS are unclear, and further methodologically sound research on specific populations is much needed before offering it clinically. Full article
(This article belongs to the Section Developmental and Reproductive Biology)
12 pages, 601 KiB  
Article
Elevated Anti-Müllerian Hormone as a Prognostic Factor for Poor Outcomes of In Vitro Fertilization in Women with Polycystic Ovary Syndrome
by Emídio Vale-Fernandes, Márcia Barreiro, Carla Leal, Rosa Zulmira Macedo, António Tomé and Mariana P. Monteiro
Biomedicines 2023, 11(12), 3150; https://doi.org/10.3390/biomedicines11123150 - 27 Nov 2023
Cited by 13 | Viewed by 3321
Abstract
Women with polycystic ovary syndrome (PCOS) tend to have elevated anti-Müllerian hormone (AMH) levels, which appear to correlate with disease severity and pregnancy outcomes. This was a retrospective observational study designed to assess the relationship between circulating AMH levels and in vitro fertilization [...] Read more.
Women with polycystic ovary syndrome (PCOS) tend to have elevated anti-Müllerian hormone (AMH) levels, which appear to correlate with disease severity and pregnancy outcomes. This was a retrospective observational study designed to assess the relationship between circulating AMH levels and in vitro fertilization (IVF) outcomes. The study involved 150 women with PCOS who underwent IVF treatments. The women’s IVF cycles were allocated into three subgroups according to AMH levels: ‘low’ (AMH < 3.7 ng/mL; n = 49), ‘middle’ (AMH 3.7–7.4 ng/mL; n = 94), and ‘high’ (AMH > 7.4 ng/mL; n = 56). All pregnancy-related outcomes (positive beta human chorionic gonadotropin (βHCG), clinical pregnancy rate, live birth rate, and cumulative live birth rate) were greater in women’s IVF cycles with ‘low’ AMH when compared to those with ‘middle’ or ‘high’ AMH (p < 0.05). AMH levels below 3.7 ng/mL were found to be associated with lower oocyte immaturity rate and better pregnancy outcomes, although baseline AMH was not shown to have any significant predictive power for live birth and cumulative live birth in the multivariable logistic regression analysis after adjusting for possible confounders nor in the ROC analyses. In summary, the current study lays the groundwork to validate high AMH levels as a poor prognostic factor for pregnancy outcomes after IVF in women with PCOS. Full article
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13 pages, 1579 KiB  
Article
The Prediction of IVF Outcomes with Autologous Oocytes and the Optimal MII Oocyte/Embryo Number for Live Birth at Advanced Maternal Age
by Jelena Havrljenko, Vesna Kopitovic, Aleksandra Trninic Pjevic, Stevan Milatovic, Tatjana Pavlica, Nebojsa Andric and Kristina Pogrmic-Majkic
Medicina 2023, 59(10), 1799; https://doi.org/10.3390/medicina59101799 - 10 Oct 2023
Cited by 9 | Viewed by 3707
Abstract
Background and Objectives: Delayed childbearing in advanced age might be associated with a low prognosis for achieving pregnancy. Therefore, it is important to establish a predictive tool that will optimize the likelihood of a live birth at advanced age. Material and Methods: The [...] Read more.
Background and Objectives: Delayed childbearing in advanced age might be associated with a low prognosis for achieving pregnancy. Therefore, it is important to establish a predictive tool that will optimize the likelihood of a live birth at advanced age. Material and Methods: The retrospective study was conducted at the Ferona Fertility Clinic in Novi Sad (Republic of Serbia), between January 2020 and May 2021. The survey included 491 women aged ≥35 who met the inclusion criteria and who were subjected to an IVF (in vitro fertilization) treatment cycle. Results: The average number of retrieved oocytes, MII (metaphase II) oocytes, and developed embryos significantly decreased in advanced age. Age was also found to have a significant adverse effect on pregnancy and live birth rates. In women aged ≥35, 10/12 MII oocytes or 10/11 embryos are required for reaching an optimal live birth rate/cumulative live birth rate. Optimal CLBR (cumulative live birth rate) per one oocyte was achieved when 9 MII oocyte were retrieved. Conclusions: The study indicates that the cut-off for increased risk is ≥42 year. However, despite low live birth rates, autologous IVF for these women is not futile. An increase in the number of retrieved mature oocytes and a generation of surplus cryopreserved embryos could reinforce LBR (live birth rate) and CLBR. Clinicians should be very cautious in counseling, as autologous IVF may only be applicable to women with good ovarian reserve. Full article
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11 pages, 637 KiB  
Article
Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study
by Ying Chen, Yifan Chu, Wen Yao, Luyao Wang, Wanjiang Zeng and Jing Yue
J. Clin. Med. 2023, 12(18), 5775; https://doi.org/10.3390/jcm12185775 - 5 Sep 2023
Cited by 5 | Viewed by 2219
Abstract
Research Question: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Design: Poor ovarian response [...] Read more.
Research Question: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Design: Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E2 was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. Results: The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). Conclusion(s): The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients. Full article
(This article belongs to the Special Issue New Advances in Clinical Reproductive Medicine)
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