To identify relationships between the size of punctured ovarian follicles and subsequent embryology outcomes.Prospective observational cohort study.Private fertility center.One hundred fifty-seven oocyte retrievals performed during the study period.The diameter of punctured follicles was ultrasonically measured during routine oocyte collection. The resulting embryos were group-cultured to the blastocyst stage and classified into 8 groups according to follicle size (≤9.5, 10-12.5, 13-15.5, 16-18.5, 19-21.5, 22-24.5, 25-27.5, and ≥28 mm).Rate of good-quality blastocysts per follicle puncture.This study included 4,539 follicle punctures, 2,348 oocytes, 1,772 mature oocytes, 1,258 bipronuclear (2pn) oocytes, and 571 good-quality blastocysts derived from 157 oocyte retrievals. The per-puncture yields of oocytes, mature oocytes, 2pn oocytes, and good-quality blastocysts were associated with the size of the punctured follicle. The rates of good-quality blastocysts per punctured follicle were 2.2% (≤9.5 mm), 6.2% (10-12.5 mm), 11.9% (13-15.5 mm), 14.5% (16-18.5 mm), 18.9% (19-21.5 mm), 17.5% (22-24.5 mm), 15.9% (25-27.5 mm), and 16.0% (≥28 mm). When compared with the overall average, punctures of follicles in groups ≤12.5 mm in diameter had significantly inferior yields of good-quality blastocysts, whereas punctures of follicles in groups 19-24.5 mm in diameter were associated with significantly greater than average yields of good-quality blastocysts. Other groups did not differ significantly from average. No correlation was observed between follicle diameter and ploidy of biopsied blastocysts.Punctures of follicles ≤12.5 mm in diameter rarely result in good-quality blastocysts. The yield of good-quality blastocysts progressively increases with follicle size up to approximately 19 mm in diameter, with no substantial decline above that size. The ploidy of the blastocysts that form appears to be unaffected by follicle size.Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years. The failure to implant may be a consequence of embryo or uterine factors. Thorough investigations should be carried out to ascertain whether there is any underlying cause of the condition. Ovarian function should be assessed by measurement of antral follicle count, FSH and anti-Mu¨llerian hormone. Increased sperm DNA fragmentation may be a contributory cause. Various uterine pathology including fibroids, endometrial polyps, congenital anomalies and intrauterine adhesions should be excluded by ultrasonography and hysteroscopy. Hydrosalpinges are a recognized cause of implantation failure and should be excluded by hysterosalpingogram; if necessary, laparoscopy should be performed to confirm or refute the diagnosis. Treatment offered should be evidence based, aimed at improving embryo quality or endometrial receptivity. Gamete donation or surrogacy may be necessary if there is no realistic chance of success with further IVF attempts.Copyright © 2013. Published by Elsevier Ltd.

What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation?

During in vitro fertilization treatment, three types of oocyte anomalies were observed in four infertile women. These anomalies were related to (1) failure of oocyte maturation from the germinal vesicle stage of meiosis, (2) failure of polar body formation and cleavage, and (3) absence of oocytes in otherwise mature follicular aspirates. These anomalies are considered to contribute to these patients' infertility.

Failure to retrieve oocytes during in vitro fertilization (IVF) treatment was recently referred to as the "empty follicle syndrome." Data on the possible repetitiveness of this during previous or subsequent IVF attempts is lacking, which limits the understanding of its significance to the involved patients. Of 26 patients who had cycles during which no oocytes were retrieved, 10 were pregnant in the past and 20 had at least one other IVF cycle that yielded oocytes. There was no difference in the frequency of any stimulation protocol among the failure cycles compared with the successful ones. Hormonal response pattern and the number of large follicles observed sonographically did not differ between the two occasions. Fertilization occurred in 70% of the successful cycles and two biochemical pregnancies were recorded. In 13 patients, at least one cycle was canceled because of poor ovarian response, but 9 of these 13 had at least one other successful cycle. We conclude that the so-called empty follicle syndrome cannot be predicted by the pattern of ovarian response and does not predict a reduced fertility potential in future cycles.

The empty follicle syndrome (EFS) is a frustrating condition in which no oocytes are retrieved in an IVF cycle. Although this is an infrequent event in IVF patients, the economic consequences as well as the emotional frustration of a cancelled cycle due to the inability to obtain oocytes are enormous. The mechanisms responsible for EFS remain obscure, though many hypotheses have been put forward ranging from dysfunctional folliculogenesis to a drug-related problem. We found that the EFS is a rare event (1.8% of oocyte retrievals) but with profound implications for counselling the couple about their future reproductive performance. The chances of recurrence of EFS increase with the age of the patient (24% recurrence rate for the 35-39 year age group, and 57% for those over 40 years). We postulate that ovarian ageing, through altered folliculogenesis, may be implicated in the aetiology of EFS and its recurrence.

To determine whether IVF or intracytoplasmic sperm injection (ICSI) should be the choice of treatment in case of a previous IVF attempt with unexplained total fertilization failure or low fertilization (<25%).Prospective study.Leiden University Medical Center.Thirty-eight couples undergoing IVF and ICSI on sibling oocytes after a first IVF attempt with total fertilization failure or with low fertilization (<25%).Performing IVF and ICSI on sibling oocytes.Fertilization and (ongoing) pregnancy rate.A total of 271 oocytes were collected in 24 oocyte retrievals in the total fertilization failure group. Hundred nine oocytes were randomly allocated to IVF and 12 were fertilized (11%); 162 sibling oocytes were allocated to ICSI and 78 were fertilized (48%). In 8 of the 24 patients fertilization occurred after IVF. The pregnancy rate after transfer of 1 IVF and 1 ICSI embryo (n = 3) was 67% and after the transfer of 2 ICSI embryos (n = 21) this was 52%. In the low fertilization group 169 oocytes were collected in 14 oocyte retrievals. Seventy-two oocytes were randomly allocated to IVF and 16 were fertilized (22%). Ninety-seven sibling oocytes were allocated to ICSI and 58 were fertilized (60%). In 7 of 14 patients fertilization occurred after IVF. The pregnancy rate after the transfer of 1 IVF and 1 ICSI embryo (n = 5) was 80% and after the transfer of 2 ICSI embryos (n = 9) this was 33%.Performing ICSI on some oocytes of a cohort may avoid total fertilization failures both in patients with a history of total fertilization failure and in patients with a history of low fertilization, as the percentage of fertilization is higher after ICSI compared to IVF and the recurrence of total fertilization failure and low fertilization is high after IVF treatment.

Infertility affects between 10 and 16% of couples worldwide. Twenty to 30% of cases of infertility are due to a male factor, 20-35% to a female factor, and 25-40% are due to both male and female factors. In ∼10-25% of cases, the precise underlying cause remains unclear. IVF or ICSI followed by embryo transfer can be very appropriate treatment options in cases of female tubal damage, ovulatory failure or male-factor infertility. While the use of IVF has been reported to be suitable for many infertile couples, normal IVF cycles can fail in some cases. While ICSI can represent a powerful alternative in cases of IVF failure, complete fertilization failure can still occur in 1-5% of ICSI cycles. This can be due to a variety of factors and while commonly attributed to deficiency of sperm factors, it is very likely that abnormalities in crucial oocyte factors could also play a key role.A critical literature review using PubMed was performed between April 2014 and July 2015 targeting studies concerning sperm and oocyte factors that could account for oocyte activation deficiency, and including studies of in vitro oocyte maturation in human oocytes, and animal models.Accumulating evidence indicates that phospholipase C zeta (PLCζ) is the sperm oocyte activation factor, although recent studies claim that another sperm protein known as post-acrosomal WWP-binding domain protein could also play a significant role in the activation of oocytes. The present review discusses our current understanding of these two proteins but emphasizes that defects in the molecular machinery within the oocyte that interacts with such sperm proteins may also represent an underlying cause of fertilization failure and infertility, especially in cases where there is no obvious indication for sperm deficiency. Abnormalities in such mechanisms are highly likely to exert influence over the pulsatile release of calcium within the ooplasm, the critical signal that controls oocyte activation events. These molecular targets within the oocyte are rarely, if ever, considered clinically. We therefore recommend that future diagnostic assays should be developed to consider the inositol triphosphate receptor, protein kinase C, proteins associated with stored operated calcium entry calcium/calmodulin-dependent protein kinase II and mitogen-activated protein kinase. Development of such assays would represent a significant step forward in the diagnosis of oocyte activation deficiency and may identify a series of potential therapeutic targets.The present review provides a general overview of how a combination of sperm and oocyte factors can underlie oocyte activation deficiency, but pays particular attention to the less appreciated role of the oocyte. Enhanced research within this realm is much warranted and may establish new approaches for the diagnosis and treatment of infertility.© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early embryonic arrest is one of the major causes of female infertility. However, because of difficulties in phenotypic evaluation, genetic determinants of human early embryonic arrest are largely unknown. With the development of assisted reproductive technology, the phenotype of early human embryonic arrest can now be carefully evaluated. Here, we describe a consanguineous family with a recessive inheritance pattern of female infertility characterized by recurrent early embryonic arrest in cycles of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We have identified a homozygous PADI6 nonsense mutation (c.1141C>T [p.Gln381(∗)]) that is responsible for the phenotype. Mutational analysis of PADI6 in a cohort of 36 individuals whose embryos displayed developmental arrest identified two affected individuals with compound-heterozygous mutations (c.2009_2010del [p.Glu670Glyfs(∗)48] and c.633T>A [p.His211Gln]; c.1618G>A [p.Gly540Arg] and c.970C>T [p.Gln324(∗)]). Immunostaining indicated a lack of PADI6 in affected individuals' oocytes. In addition, the amount of phosphorylated RNA polymerase II and expression levels of seven genes involved in zygotic genome activation were reduced in the affected individuals' embryos. This phenotype is consistent with Padi6 knockout mice. These findings deepen our understanding of the genetic basis of human early embryonic arrest, which has been a largely ignored Mendelian phenotype. Our findings lay the foundation for uncovering other genetic causes of infertility resulting from early embryonic arrest.Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Successful human reproduction requires normal spermatogenesis, oogenesis, fertilisation and early embryonic development, and abnormalities in any of these processes will result in infertility. Early embryonic arrest is commonly observed in infertile patients with recurrent failure of assisted reproductive technology (ART). However, the genetic basis for early embryonic arrest is largely unknown.

Successful human reproduction initiates from normal gamete formation, fertilization and early embryonic development. Abnormalities in any of these steps will lead to infertility. Many infertile patients undergo several failures of IVF and intracytoplasmic sperm injection (ICSI) cycles, and embryonic developmental arrest is a common phenotype in cases of recurrent failure of IVF/ICSI attempts. However, the genetic basis for this phenotype is poorly understood. The subcortical maternal complex (SCMC) genes play important roles during embryonic development, and using whole-exome sequencing novel biallelic mutations in the SCMC genes TLE6, PADI6 and KHDC3L were identified in four patients with embryonic developmental arrest. A mutation in TLE6 was found in a patient with cleaved embryos that arrested on day 3 and failed to form blastocysts. Two patients with embryos that arrested at the cleavage stage had mutations in PADI6, and a mutation in KHDC3L was found in a patient with embryos arrested at the morula stage. No mutations were identified in these genes in an additional 80 patients. These findings provide further evidence for the important roles of TLE6, PADI6 and KHDC3L in embryonic development. This work lays the foundation for the genetic diagnosis of patients with recurrent IVF/ICSI failure.Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Controlled ovarian hyperstimulation (COH) is routinely used in the fertilization and embryo transfer (IVF-ET) cycles to increase the number of retrieved mature oocytes. However, the relationship between repeated COH and ovarian function is still controversial. Therefore, we investigated whether repeated ovarian stimulation affects ovarian aging and function, including follicular development, autophagy, and apoptosis in follicles. Ovarian hyperstimulation in mice was induced by intraperitoneal injection with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Mice subjected to ovarian stimulation once were used as a control group and 10 times as an experimental group. Repeated injections with PMSG and hCG significantly reduced the number of primary follicles compared to a single injection. The number of secondary and antral follicles increased slightly, while the number of corpus luteum increased significantly with repeated injections. On the other hand, repeated injections did not affect apoptosis in follicles associated with follicular atresia. The expression of autophagy-related genes,,, and, cell proliferation-related genes, apoptosis-related genes, and was not significantly different between the two groups. In addition, the expression of the aging-related genes,, and were also not significantly different. In this study, we demonstrated that repeated ovarian stimulation in mice affects follicular development, but not autophagy, apoptosis, aging in ovary. These results suggest that repetition of COH in the IVF-ET cycle may not result in ovarian aging, such as a decrease in ovarian reserve in adult women.© Copyright 2021 The Korean Society of Developmental Biology.

This study was designed to assess the ovarian response in the same patient in consecutive IVF cycles.Retrospective study.Assisted reproductive unit at a university hospital.One hundred ninety women who underwent three consecutive cycles of IVF.All women used a combination of pituitary desensitization and gonadotropin stimulation protocol and underwent oocyte retrieval.Number of follicles produced and number of oocytes retrieved.There were no significant differences in the number of follicles produced, number of oocytes retrieved, and number of embryos created by the same woman among the three cycles of treatment.Consistent ovarian response can be achieved during the first three consecutive IVF cycles.

After a failed in vitro fertilization (IVF) procedure in which no transferable embryo was obtained, the possibility of a subsequent pregnancy for the patient is unknown. We conducted a cohort retrospective study evaluating the live birth rate in the subsequent cycles of the patients with no embryo for transfer in their first IVF attempt between 2017and 2020. The first cycle variables of patients who conceived in subsequent cycles were compared to those who did not. Additionally, for patients who conceived at last, variables related to ovarian stimulation were compared between the first cycle and the conceiving cycle. In accordance with the inclusion criteria, 529 were enrolled during the study period, of which 230 had successful pregnancies and 192 gave birth to a live infant. Cumulative live birth rates (CLBR) per cycle and patient were 26% and 36% respectively. Moreover, 99% of the live births were obtained within the first three attempts, beyond six cycles, there was no pregnancy. Stimulating variables in the first cycle were not effective in predicting the likelihood of a patient's subsequent pregnancy. Overall, patients who did not have embryos available for transfer in the first cycle had a 36% chance of getting a live birth in subsequent attempts, and the cause of failure should be considered.© 2023. The Author(s).

The utilization of donor eggs has broadened the options for Assisted Reproductive Technology (ART) among women facing challenges with egg quantity or quality. Given that donors are typically selected from young and fertile individuals, In Vitro Fertilization with egg donation (IVF-ED) tends to exhibit higher rates of implantation, pregnancy, and live births compared to IVF with the woman's own eggs, especially for females over 35 years old. This has led to a projected increase in the demand for IVF-ED, surpassing the number of available donors. Consequently, many centers opt to use oocyte donors for multiple cycles. However, the correlation between repeated Controlled Ovarian Stimulation (COS) cycles and the performance of donors in terms of viable blastocyst stage embryo (VEC) or blastocyst embryo rate is not definitively established and remains of interest. This study aims to explore the preimplantation characteristics of embryo development and oocyte maturation status based on the number of donor COS cycles, employing a Generalized Linear Mixed Model (GLMM) framework. The study encompasses 1965 embryo transfer (ET) cycles involving 399 donors who underwent a minimum of two and a maximum of nine controlled ovarian hyperstimulation (COS) cycles. The findings indicate that, with the patient undergoing six or more cycles of ovarian stimulation, despite a 3.9% increase in both maturation and fertilization rates, there is a corresponding decrease of 4.5% in VEC rate and 4.7% in blastulation rates. In essence, an escalating number of donor COS cycles appears to be associated with a disadvantageous reduction in embryo quality.© 2024. The Author(s).

This study assessed the impact of increased initial gonadotropin doses on ovarian stimulation (OS) outcomes in unexpected hypo-responders [Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) 1-2 group] with suboptimal mature oocyte yield, despite normal ovarian reserve markers, during their first OS cycle.Conducted at a referral infertility clinic, this observational study included women who retrieved fewer than nine oocytes during their first OS cycle despite gonadotropin doses of 150-225 international unit (IU)/day starting from cycle day two. Women who underwent a second OS cycle following unsuccessful conception were included. Gonadotropin doses were increased to 225 or 300 IU recombinant follicle-stimulating hormone (FSH) (recFSH) based on body mass index. Each patient served as her own control, with first and second OS cycles compared in terms of oocyte yield, follicular output ratio (FORT), and follicle-to-oocyte index (FOI).Among 289 unexpected hypo-responders (12% prevalence), the mean age was 34.2 years, and the mean anti-müllerian hormone level was 3.4 ng/mL. The stimulation duration was similar between cycles (11.2 days). The second OS cycle showed significant improvements in total oocytes, metaphase II oocytes, FORT, FOI, cleavage-stage embryos, and blastocysts (p<0.05).Increasing gonadotropin doses in subsequent cycles improves oocyte yield and embryological outcomes in unexpected hypo-responders (POSEIDON 1-2) with normal ovarian reserve markers.Copyright© 2025 The Author. Published by Galenos Publishing House on behalf of Turkish Society of Obstetrics and Gynecology.

To evaluate whether physicians' choice of ovarian stimulation protocol is associated with laboratory outcomes.Retrospective cohort study.Single academic center.The subjects were 4,458 patients who completed more than one in vitro fertilization ovarian stimulation cycle within 1 year. On second stimulation, 49% repeated the same protocol and 51% underwent a different one.Estradiol priming antagonist, antagonist +/- oral contraceptive pill priming, long luteal protocol, Lupron (Lupron [AbbVie Inc, North Chicago, IL]) stop protocol, and flare were compared. Logistic or linear regression with cluster robust standard errors to account for covariates and paired data was used.Oocytes collected (OC), fertilization rate, blastocyst progression (BP), usable embryos (UE), and euploid rate (ER).First stimulation outcomes were comparable across all protocols for FR, BP, UE, and ER but were different for OC, after adjustment for covariates. For OC, the effect of switching protocols differed according to the type of the second stimulation. There was improvement in OC if the same stimulation was repeated, except for flare. In addition, there were slight, significant improvements in fertilization rate (difference in values or coefficient of 0.02; 95% confidence interval [CI], 0.004, 0.4) and UE (coefficient 1.25; 95% CI, 0.79, 1.72) when the same stimulation was repeated. There were no changes in BP (coefficient 0.03; 95% CI, -0.01, 0.08) or ER (coefficient 0.01; 95% CI, -0.04, 0.06) when protocols were changed. In a low-BP subgroup, greater improvement was seen when the same protocol was repeated (coefficient 0.03; 95% CI 0.01, 0.04).There was a slight but significant improvement in laboratory outcomes when the same stimulation protocol was repeated, so careful consideration should be made before switching stimulation protocols for the purpose of improving laboratory outcomes.Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The LH/chorionic gonadotropin receptor (LHCGR) is mainly expressed in gonads and plays important roles in estradiol production, ovulation, and luteal formation. Women with pathogenic LHCGR variants suffer from infertility, and successful fertility treatments for such women have never been reported.The purpose of this study was to determine whether women with pathogenic LHCGR variants can achieve successful pregnancies through in vitro fertilization.Three women with LH resistance and infertility and their parents underwent exome sequencing. The biochemical characteristics and functional effects of LHCGR mutation were assessed in transfected human embryonic kidney -293T cells and primary granulosa cells.All affected women harbored pathogenic LHCGR variants. The LHCGR variants lacked cell surface localization and signal transduction abilities in vitro and in vivo. After dual triggering and prolonging the interval between triggering and oocyte pick-up, all three patients achieved oocytes and high-quality embryos. After frozen embryo transfer, one woman successfully birthed twins, and one woman successfully birthed a live boy. Apart from difficulties in oocyte retrieval, no obvious abnormalities in fertilization or during embryo development and pregnancy were identified in these patients.This study is, to our knowledge, the first to report successful assisted reproductive treatment of women with pathogenic LHCGR variants using their own oocytes. Our results supported that defects in LHCGR disrupted ovulation but had no effect on fertilization and embryo development.Copyright © 2019 Endocrine Society.