Standard In Vitro Fertilization Research Articles

Development and validation of a clinical prediction model of fertilization failure during routine IVF cycles.

This study aims to create and validate a clinical model that predict the probability of fertilization failure in routine in-vitro fertilization (IVF) cycles. This study employed a retrospective methodology, gathering data from 1770 couples that used reproductive center's of the Fourth Hospital of Hebei Medical University standard IVF fertilization between June 2015 and June 2023. 1062 were in the training set and 708 were in the validation set when it was randomly split into the training set and validation set in a 6:4 ratio. The study employed both univariate and multivariate logistic regression analysis to determine the factors those influence the failure of traditional in vitro fertilization. Based on the multiple regression model, a predictive model of traditional IVF fertilization failure was created. The calibration and decision curves were used to assess the effectiveness and therapeutic usefulness of this model. The following factors independently predicted the probability of an unsuccessful fertilization: infertility years, basal oestrogen, the rate of mature oocytes, oligoasthenozoospermia, sperm concentration, sperm vitality, percentage of abnormal morphological sperm, and percentage of progressive motility (PR%).The receiver operating characteristic curve's area under the curve (AUC) in the training set is 0.776 (95% CI: 0.740,0.812), while the validation set's AUC is 0.756 (95% CI: 0.708,0.805), indicating a rather high clinical prediction capacity. Our generated nomogram has the ability to forecast the probability of fertilization failure in couples undergoing IVF, hence can assist clinical staff in making informed decisions.

Outcomes of the Next In Vitro Fertilization Cycle in Women with Polycystic Ovary Syndrome after a Failed In Vitro Maturation Attempt.

In vitro maturation (IVM) is indicated in women with polycystic ovary syndrome (PCOS) who have a very good ovarian response during in vitro fertilization (IVF) and are therefore at high risk of ovarian hyperstimulation syndrome (OHSS). According to the latest practice committee document, IVM could be a major advance in assisted reproductive technology (ART) procedures (reduced cost and simplified treatment); nevertheless, retrospective studies of IVM versus IVF still demonstrate lower chances of a live birth with IVM. Could IVM prove to be an optimal first-line treatment approach? And limited information is available concerning the success of the subsequent IVF cycle after the failure of an IVM cycle. Does IVM treatment adversely affect the subsequent IVF cycle, and is this worth considering before performing the IVF cycle for women with PCOS? This prospective nested case-control study at the Peking University Reproductive Medicine center in China was performed between March 2018 and September 2020. Women aged 20-38 years with PCOS and infertility and who were scheduled for their first IVF attempt were eligible. A total of 351 women were randomly allocated to receive one cycle of unstimulated natural IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol followed by hCG as an ovulation trigger (n = 176). This study involved 234 women (58 women with no blastocysts in the first IVM cycle and 158 women who underwent the first IVF cycle). Cumulative live birth rate at 12 months after oocyte retrieval and OHSS of a standard controlled ovarian stimulation (COS) IVF cycle were compared between 58 women in an IVF cycle following a failed IVM cycle and 158 women who underwent the first IVF cycle. No significant differences were found in the cumulative live birth rate (CLBR), ongoing pregnancy rate, or clinical pregnancy rate at 12 months after oocyte retrieval between the two groups (56.9% vs. 58.9%, p = 0.795; 58.6% vs. 60.8%, p = 0.776; and 84.5% vs. 76.0%, p = 0.178). The incidence of moderate-to-severe OHSS was not significantly different between the groups (6.9% vs. 5.7%, p = 0.742). Additionally, there were no significant differences in the total gonadotropin dose, stimulation duration, number of retrieved oocytes, number of retrieved mature oocytes, or fertilization rates. Even if the first IVM attempt failed in subfertile women with PCOS, comparable cumulative live birth rates were observed in the subsequent IVF cycle. IVM treatment does not adversely affect the subsequent IVF cycle.

Sperm deoxyribonucleic acid fragmentation index at the time of intracytoplasmic sperm injection and standard in vitro fertilization is correlated with lower fertilization but not with blastocyst genetic diagnosis

To determine the effects of sperm deoxyribonucleic acid (DNA) fragmentation at the time of fertilization on invitro fertilization (IVF) outcomes and genetic diagnosis using next generation sequencing. Prospective double-blinded study. Private Clinic. Couples (n = 150). Invitro fertilization with preimplantation genetic testing for aneuploidy and sperm DNA fragmentation assay, as in sperm chromatin structure assay the day of retrieval. Laboratory outcomes are listed in the results section. Statistical analysis was performed using JMP, XYLSTAT, and STATA version15. The sperm DNA fragmentation index (DFI) in the neat ejaculate did not predict fertilization rate, quality, blastulation, or genetic diagnosis. No statistically significant results were obtained comparing <15% with >15%, <20% with >20%, <30% with >30% except for DFI. No statistically significant differences in oocyte source age or male age were observed. No statistically significant differences comparing <15% with >15%, <20% with >20%, <30% with >30% DFI at the time of standard IVF or intracytoplasmic sperm injection (ICSI) were observed for % euploid, aneuploid, mosaic, blastulation, biopsied, or D5/total biopsied. The DFI of >15% had more good quality D3 embryos than the <15% group, as did the >20% group compared with the <20% group. The ICSI fertilization was significantly higher in all 3 lower percentage groups compared with the higher counterpart. Standard IVF had significantly more blastocysts/fertilized suitable for biopsy and more D5/total number biopsied than ICSI embryos despite no difference in DFI. The DFI at fertilization is correlated with decreased fertilization for ICSI and IVF.

Polymorphism of the follicle stimulating hormone receptor does not impact reproductive performance or in-vitro embryo production in beef heifers

Assisted reproductive technologies are used to propagate desirable genetics in a shortened timeframe. Selected females undergo ovarian stimulation with the use of follicle stimulating hormone (FSH) to increase embryo recovery for subsequent transfer programs. The FSH receptor (FSHR) c.337 C > G variant was reported to have a reduction in viable embryo numbers in an ovarian stimulation protocol. We, therefore, hypothesized that FSHR c.337 C > G would result in reduced in-vitro blastocyst development. Beef heifers were genotyped and selected based on the c.337 C > G FSHR genotype (CC, CG, GG; n = 15–16/genotype). Estrus was synchronized with a Select Synch protocol and heifers were slaughtered 5 days after induced ovulation. Anterior pituitaries, serum and reproductive tracts were collected at slaughter for analysis. Cumulus oocyte complexes (COCs) were collected and pooled within genotype for in-vitro fertilization (IVF) and subsequent blastocyst development. No differences were observed in carcass weights, anterior pituitary weights, serum progesterone, corpus lutea weight, surface follicle counts, histological follicle counts or follicular fluid estradiol concentration (P > 0.1) due to FSHR genotype. Differences were observed for ovulation rates in the GG FSHR genotype group (P < 0.01). However, cleavage and blastocyst rates were not affected due to FSHR genotype (P > 0.1), following standard IVF protocols. The FSHR variant does not influence antral follicle counts, estradiol production, or in-vitro blastocyst development in beef heifers. The GG FSHR genotype had an increased ovulation rate, which may indicate a greater potential for twinning, but research with a larger population is warranted to support this hypothesis.

WHAT ARE THE PATIENTS’ OPINIONS CONCERNING THE USE OF “ADD-ONS” ON REPRODUCTIVE MEDICINE? A SURVEY OF IVF PATIENTS

In vitro fertilization (IVF) 'add-ons' are adjunct treatments used in addition to standard IVF protocols, in attempts to improve success rates. However, the benefits for add-ons are often not supported by high-quality evidence. Despite that, many infertile patients are willing to try anything that might help them improve their chances of having a baby. Therefore, the use of add-ons has been widespread, leading to extensive debate and discussion. The goal for the present study was to evaluate the intention to use add-ons to increase the chance of success, among infertile patients, who have already started or will start an IVF treatment.

Human Blastocyst Components Detection Using Multiscale Aggregation Semantic Segmentation Network for Embryonic Analysis.

Infertility is one of the most important health concerns worldwide. It is characterized by not being successful of pregnancy after some periods of periodic unprotected sexual intercourse. In vitro fertilization (IVF) is an assisted reproduction technique that efficiently addresses infertility. IVF replaces the actual mode of reproduction through a manual procedure wherein embryos are cultivated in a controlled laboratory environment until they reach the blastocyst stage. The standard IVF procedure includes the transfer of one or two blastocysts from several blastocysts that are grown in a controlled environment. The morphometric properties of blastocysts with their compartments such as trophectoderm (TE), zona pellucida (ZP), inner cell mass (ICM), and blastocoel (BL), are analyzed through manual microscopic analysis to predict viability. Deep learning has been extensively used for medical diagnosis and analysis and can be a powerful tool to automate the morphological analysis of human blastocysts. However, the existing approaches are inaccurate and require extensive preprocessing and expensive architectures. Thus, to cope with the automatic detection of blastocyst components, this study proposed a novel multiscale aggregation semantic segmentation network (MASS-Net) that combined four different scales via depth-wise concatenation. The extensive use of depthwise separable convolutions resulted in a decrease in the number of trainable parameters. Further, the innovative multiscale design provided rich spatial information of different resolutions, thereby achieving good segmentation performance without a very deep architecture. MASS-Net utilized 2.06 million trainable parameters and accurately detects TE, ZP, ICM, and BL without using preprocessing stages. Moreover, it can provide a separate binary mask for each blastocyst component simultaneously, and these masks provide the structure of each component for embryonic analysis. Further, the proposed MASS-Net was evaluated using publicly available human blastocyst (microscopic) imaging data. The experimental results revealed that it can effectively detect TE, ZP, ICM, and BL with mean Jaccard indices of 79.08, 84.69, 85.88%, and 89.28%, respectively, for embryological analysis, which was higher than those of the state-of-the-art methods.

P-781 Elective single cleavage-stage embryo transfer in IVF patients with suboptimal ovarian response is not detrimental to cumulative pregnancy and reduces multiple pregnancy rates

Abstract Study question To compare elective single embryo transfer (eSET) with double embryo transfer (DET) in patients with suboptimal response to ovarian stimulation in terms of pregnancy rates. Summary answer Elective single embryo transfer in patients with suboptimal response to ovarian stimulation is not detrimental to cumulative pregnancy and delivery rates. What is known already Even though higher-order pregnancies in in vitro fertilization (IVF) programs have dropped significantly in recent years, the incidence of twin pregnancies is currently not negligible. The greatest efforts to promote eSET have been made in the IVF population with a good prognosis but results obtained in this population can hardly be extrapolated to patients with lower chances of success, such as those with low oocyte yield. Although still under discussion, it has been suggested that in patients with poor or suboptimal response to ovarian stimulation, eSET could achieve acceptable cumulative live birth rates with negligible risk of twin pregnancy. Study design, size, duration A matched case-control pre and post intervention study including IVF patients with poor or sub-optimal response to ovarian stimulation (≤9 oocytes) receiving a double embryo transfer (2016-2018) or elective single embryo transfer (2018-2020). Matching was performed 1:1 for female age (±18 months), AMH ≥1.2 or &amp;lt; 1.2 ng/ml and number of previous cycles. A sample size of 215 patients per group was foreseen to obtain ±5% variability of the main outcome (clinical pregnancy rate per cycle). Participants/materials, setting, methods A strict policy regarding single embryo transfer was introduced in our clinic from September 2018 to reduce twin pregnancy rates independently from ovarian response or embryo quality. Couples undergoing standard IVF or ICSI with ≤9 oocytes and at least 2 viable embryos were divided in two groups and matched for main variables known for influencing results: pre-intervention with DET (controls) and post-intervention with eSET (cases). In both groups, cryopreserved supernumerary embryos were always transferred individually. Main results and the role of chance A total of 463 patients with at least 2 viable embryos undergoing fresh embryo transfer after the recovery of 2 to 9 oocytes were retrospectively evaluated and, according to matching criteria, 212 cases (eSET) and 212 matched controls (DET) were included for data analysis. The cumulative clinical pregnancy rate per cycle was the same in the two groups (26%, 95%CI: 20-32%) with a crude OR = 1.00 (95%CI: 0.65-1.54), p = 1.00 and a mean female age of 37.4 and 38.0 years, respectively. The mean number of mature oocytes was 4 ±2 in both groups. Live birth rate was similar in cases and controls (22% and 21%, respectively) while twin pregnancies were significantly reduced in women receiving single embryo transfer (18% versus 0%, p = 0.008). Women receiving eSET were more likely to undergo a subsequent frozen embryo transfer (26% versus 14%, p = 0.002). Considering the main confounding factors, a binomial logistic model indicated that the cumulative clinical pregnancy rate was not significantly affected when a single embryo transfer was performed in women recovering up to nine oocytes. Similar results were obtained comparing cases and controls within subgroups: 2-4 or 5-9 oocytes; &amp;lt;35 or 35–39 or &amp;gt; 39 years female age). Limitations, reasons for caution This study does not have the statistical power to highlight small differences between the two groups. It was conducted on a specific population of women with 9 or less oocytes therefore results cannot be generalized to other populations, particularly those with a better or poorer prognosis. Wider implications of the findings eSET results are mainly based on good prognosis couples. Despite a trend for better success after fresh DET, cumulative results are not affected by eSET at the cleavage stage with significantly reduced incidence of twins and moderate delay in time to pregnancy also in poor/suboptimal responders. Trial registration number not applicable

O-044 ICSI in the lab: from vintage to AI

Abstract With the advent of in vitro fertilization (IVF) by Patrick Steptoe and Bob Edwards in the late 70s, the first conception outside of the human body resulted in the birth of Louise Brown. Although a terrific success, limitations of IVF surfaced, represented by the unexpected complete fertilization failure with suboptimal or dysfunctional spermatozoa. This prompted curiosity toward individual spermatozoa for a deeper understanding of its role aimed at enhancing the interaction between complementary gametes. Techniques were designed to manipulate the oocytes, such as stripping, partially digesting, or cracking the zona pellucida (ZP). These methods were palliative solutions to overcome fertilization failure and were often plagued by polyspermy. As a result, more direct approaches were implemented to overcome the ZP, such as subzonal injection (SUZI) that although more consistent, was still unable to overcome the shortcomings of dysfunctional spermatozoa. This laid the foundation for the utilization of ICSI that, whilst attempted by some investigators, became popular when Gianpiero Palermo serendipitously inserted one spermatozoon into the ooplasm during SUZI. Consistent fertilization then followed by injecting a cohort of oocytes by ICSI in SUZI cycles, and replacement of these embryos led to 4 pregnancies described in the first clinical ICSI report. To minimize oocyte damage, the procedure was further refined by inducing a deep invagination of the oolemma toward the 9 o’clock position, granting higher chances of post-injection survival. What set apart ICSI from other forms of ART was that any sperm sample, regardless of quality/quantity, would yield fertilization. Indeed, ICSI is the sole insemination method used with epididymal and testicular spermatozoa and has therefore revolutionized fertility treatment of azoospermic men. Indeed, even immotile testicular spermatozoa can still fertilize and yield successful pregnancies, albeit at a lower rate than their motile counterpart. Also, for these semen sources, aggressive sperm immobilization was introduced to enhance sperm membrane permeabilization and grant optimal fertilization results. Furthermore, ICSI has transformed the field of reproductive medicine by assisting other reproductive techniques, such as testing embryos for single gene defects to reduce the occurence of sperm DNA contamination, or overcoming the cryostress-induced changes of the ZP during cryopreservation allowing the oocyte to be fertilized at a higher rate. Oocyte cryopreservation now empowers women in their reproductive age to ordain their childbearing future. ICSI has proven to be the ultimate technique to overcome male infertility and has broadened its indication by yielding consistent fertilization and successful pregnancies in most circumstances, ensuring that men have the chance of fathering their own progeny. To date, ICSI is applied in several countries, and in some, is performed as the preferred/sole insemination method contributing to the birth of millions of babies worldwide. Thus far, no concerning differences have been seen in the health of ICSI versus standard IVF offspring, or even naturally conceived. In fact, it has been currently established that young adults of both genders born through ICSI retain their reproductive health. Despite its growing popularity, ICSI does not always succeed but still provides an invaluable platform to deepen our knowledge of gamete biology and helps to investigate/overcome some of the most severe and persistent forms of infertility. For example, combined with assisted gamete treatment, ICSI allows couples plagued by sperm-bound oocyte-activation-deficiency to achieve pregnancy. The need to increase access and curtail costs of reproductive care has led to the testing of automation in ART. This is also occurring with ICSI and to date, different automated modules have been proposed for oocyte denudation, sperm tracking, and robotic ICSI. Concurrently, there has been an interest in experimenting with artificial intelligence in the IVF laboratory to minimize human shortcomings and ensure that the best spermatozoon is chosen.

Redox state as assessed using the measurement of human non-mercaptalbumin in embryo culture media is associated with successful embryo development in human in vitro fertilization.

The role of oxidative stress in the pathogenesis of various diseases has been attracting attention. We speculated as to whether the redox state of treatment solutions used for various diseases may play a role in treatment success. In the current study, we focused on the human embryo culture medium used for in vitro fertilization (IVF). A total of 173 oocytes from a total of 91 patients treated with IVF were enrolled. The redox state was assessed by measuring the levels of human non-mercaptalbumin (HNA). We analyzed factors related to blastocyst formation on day 5 or 6 after insemination. We also developed a random forest (RF) model for the prediction of blastocyst formation. The variable importance in the predictive model was assessed using the mean decrease in the Gini impurity. Blastocyst formation was observed in 41.04% (71/173) of the oocytes and was associated with a lower %HNA in the culture medium, a younger patient age, and the fertilization method (standard IVF or intracytoplasmic sperm injection). The RF model developed using these factors and 70% of the samples (training set, n = 121) was validated in the remaining testing set (n = 52) and produced an area under the curve of 0.761, where the %HNA in the culture medium was the most important variable for predicting blastocyst formation. In conclusion, lower levels of oxidative stress in embryo culture media were associated with the success of IVF treatment. The redox state of treatment solutions should be considered to support treatment success.

Growth hormone for in vitro fertilisation (IVF).

Growth hormone for in vitro fertilisation (IVF).

O-166 A smartphone video clip on the patient journey to reduce patient’s anxiety: a randomized controlled trial

Abstract Study question Can a smartphone video clip detailing the patient journey decrease the anxiety of women and men on the day of their first oocyte aspiration? Summary answer The video clip does not affect the anxiety of women but does reduce the anxiety of men on the day of couples’ first oocyte aspiration. What is known already Infertility and in vitro fertilisation (IVF) decrease the personal wellbeing of women and men. Couples shared that this contributed to their IVF discontinuation despite a good prognosis and reimbursement of IVF. Previous longitudinal studies confirmed that pre-IVF anxiety is associated with IVF discontinuation. Limiting treatment anxiety is, therefore, relevant for fertility patients and clinics. Studies from the field of reproductive medicine examining the effect of preparatory information on anxiety suggest that focussed interventions seem more effective than complex interventions. Several randomized controlled trials (RCTs) found that preparatory information movies reduce anxiety for out-patient cardiology procedures in women and men. Study design, size, duration This monocentric RCT randomized (1:1 allocation; computerized) 190 heterosexual couples about to start their first IVF cycle between care as usual (i.e. preparatory information session 1-3 months before IVF) and care as usual combined with a novel intervention during a 24 months recruitment period (2018-2020). The novel intervention is a 5-minute smartphone video clip detailing the patient journey on the day of oocyte aspiration, which was sent to both partners the day before oocyte aspiration. Participants/materials, setting, methods Upon arrival at a private fertility clinic for their first oocyte aspiration women and men independently filled out the ‘STAI-State anxiety inventory’ and the ‘infertility distress scale (IDS)’ and evaluated the novel intervention, if applicable. A minority of randomized couples didn’t comply with the standard IVF trajectory (n = 27) or didn’t fill out the questionnaires (n = 8). The data of 155 couples (76-79/group, a-priori sample size calculation requested minimally 76/group) was subjected to a modified intention-to-treat analysis. Main results and the role of chance Women and men were on average 33 and 35 years old, respectively. Couples had a mean duration of infertility of 27 months and 63 of them (41%) had tried intrauterine insemination. The background variables were equally distributed between the intervention (IG) and control group (CG). The video clip did not affect women’s anxiety on the day of oocyte aspiration (mean STAI-State score IG 42.7±8.1 vs CG 42.1±8.5, p = 0.67). However, men who watched the video clip were significantly less anxious than men who did not watch it (mean STAI-State score IG 35.8±6.4 vs CG 38.2±7.6, p = 0.04). Surprisingly, infertility-specific distress was higher among women and men who watched the video clip (mean IDS scores of 25.8±4.9 and 22.6±5.0, respectively), as compared to women (p = 0.05) and men (p = 0.02) who did not watch the video clip (mean IDS score 24.3±4.6 and 20.8±4.7, respectively). All women and men of the intervention group, except one woman, would recommend the video clip to friends and family going through IVF. The intervention and control group did not differ significantly regarding clinical pregnancy rate (31/76 vs. 29/79, p = 0.60) or miscarriage rate (2/76 vs. 3/79, p = 0.68) 12 weeks after their first oocyte aspiration. Limitations, reasons for caution Patients nor assessors were blinded and there was no attention control group. Selection bias is plausible although the participation rate was 89%. Assessing infertility-specific distress the day after watching the video clip was not optimal, as priming couples to feel infertility-specific distress short term is less problematic than longer term. Wider implications of the findings Providing additional procedural information is interesting for clinics as patients recommended the video clip and as it decreased men’s anxiety. A follow-up study should examine whether the video clip’s priming effect on infertility-specific distress lasts longer than only the day after and whether the video clip affects IVF discontinuation. Trial registration number NCT03717805

Live birth achieved despite the absence of ejaculated spermatozoa and mature oocytes retrieved: a case report

The most common reason for in vitro fertilization (IVF) cycle cancelation is a lack of quality gametes available for intracytoplasmic sperm injection (ICSI). Here we present the successful fertility treatment of the couple affected by obstructive azoospermia combined with suboptimal response to controlled ovarian stimulation. Since the conventional approach appeared ineffective to overcome both partnersˈ specific problems, the targeted interventions, namely, (1) pharmacological enhancement of sperm motility and (2) polarized light microscopy (PLM)-guided optimization of ICSI time, were applied to rescue the cycle with only immature oocytes and immotile testicular sperm retrieved. The treatment with theophylline aided the selection of viable spermatozoa derived from cryopreserved testicular tissue. When the traditional stimulation protocol failed to produce mature eggs, non-invasive spindle imaging was employed to adjust the sperm injection time to the maturational stage of oocytes extruding a polar body in vitro. The fertilization of 12 late-maturing oocytes yielded 5 zygotes, which all developed into blastocysts. One embryo was transferred into the uterus on day 5 post-fertilization, and another 3 good quality blastocysts were vitrified for later use. The pregnancy resulted in a full-term delivery of a healthy child. This case demonstrates that the individualization beyond the standard IVF protocols should be considered to maximize the chance of poor-prognosis patients to achieve pregnancy with their own gametes.

Ceratonia siliqua (Carob) extract improved in vitro development of vitrified-warmed mouse germinal vesicle oocytes: assessment of possible mechanism.

Oocyte banking is a vital step for safekeeping and spreading genetic resources of animals. It is also used for fertility preservation of human. Oocyte vitrification is closely related to the lower developmental competence which includes the cryo-injury arisen during vitrification. The aim of the present study was to evaluate the maturation, embryonic development and production of reactive oxygen species (ROS) of mice oocytes following the supplementation vitrification media with different concentrations of Ceratonia siliqua (carob) extracts. In this experimental study, germinal vesicle oocytes collected from 8 to 10week-old female NMRI mice (30-40gr) were randomly divided into six groups of vitrification media supplemented with 0 (control), 5, 10, 20, 30 and 50µg/ml C. siliqua. After thawing, oocytes were put in an in vitro maturation medium (IVM) (α-MEM: Alpha Minimum Essential Medium). 3-4 and 24h (hr) later, the oocyte nuclear maturity was checked. Standard invitro fertilization was performed on the matured oocytes (MII), and embryonic development was followed. Extra- and intra-cellular ROS was measured in IVM medium after 24h of oocyte incubation. The addition of 20 and 30μg/ml C. siliqua extract to vitrification media improved normal morphology of warmed germinal vesicle (GV) oocytes, rate of germinal vesicle break down (GVBD), and metaphase 2 (MII) oocyte formation significantly (p < 0.05). Fertilization rate, (embryonic development to 2 cells stage, 4-8 cells stage, and > 8 cells stage increased in the 30μg/ml C. siliqua group significantly (p < 0.05). Furthermore, supplementation of 30μg/ml C. siliqua in vitrification media significantly decreased extra- and intra-cellular of ROS as well as embryonic fragmentation (p < 0.05). In conclusion, supplementation of GV oocyte vitrification media with carob extract improved maturation, fertilization, and embryonic development rate and decreased extra- and intra-cellular ROS levels.

TILT: Time-Lapse Imaging Trial\u2014a pragmatic, multi-centre, three-arm randomised controlled trial to assess the clinical effectiveness and safety of time-lapse imaging in in vitro fertilisation treatment

BackgroundSubfertility is a common problem for which in vitro fertilisation (IVF) treatment is commonly recommended. Success rates following IVF are suboptimal and have remained static over the last few years. This imposes a considerable financial burden on overstretched healthcare resources. Time-lapse imaging (TLI) of developing embryos in IVF treatment is hypothesised to improve the success rates of treatment. This may be either by providing undisturbed culture conditions or by improving the predictive accuracy for optimal embryo selection from a cohort of available embryos. However, the current best evidence for its effectiveness is inconclusive.MethodsThe time-lapse imaging trial is a pragmatic, multi-centre, three-arm parallel-group randomised controlled trial using re-randomisation. The primary objective of the trial is to determine if the use of TLI or undisturbed culture in IVF treatment results in a higher live birth rate when compared to current standard methods of embryo incubation and assessment. Secondary outcomes include measures of clinical efficacy and safety. The trial will randomise 1575 participants to detect an increase in live birth from 26.5 to 35.25%.DiscussionIn the absence of high-quality evidence, there is no current national guidance, recommendation or policy for the use of TLI. The use of TLI is not consistently incorporated into standard IVF care. A large, pragmatic, multi-centre, trial will provide much needed definitive evidence regarding the effectiveness of TLI. If proven to be effective, its incorporation into standard care would translate into significant clinical and economic benefits. If not, it would allow allocation of resources to more effective interventions.Trial registrationISRCTN registry ISRCTN17792989. Prospectively registered on 18 April 2018

Preimplantation genetic diagnosis for retinoblastoma survivors: a cost-effectiveness study.

This study aimed to investigate the cost-effectiveness of preimplantation genetic diagnosis (PGD) for the reproductive choices of patients with heritable retinoblastoma. The study modelled the costs of three cycles of in-vitro fertilization (IVF) and PGD across all uptake rates of PGD, number of children affected with retinoblastoma at each uptake rate and the estimated quality-adjusted life years (QALYs) gained. Cost-effectiveness analysis was conducted from the Australian public healthcare perspective. The intervention was the use of three cycles (one fresh and two frozen) of IVF and PGD with the aim of live births unaffected by the retinoblastoma phenotype. Compared with the standard care pathway (i.e. natural pregnancy), IVF and PGD resulted in a cost-saving to 18 years of age of AUD$2,747,294 for a base case of 100 couples with an uptake rate of 50%. IVF and PGD resulted in fewer affected (n = 56) and unaffected (n = 78) live births compared with standard care (71 affected and 83 unaffected live births), and an additional 0.03 QALYs per live birth. This modelling suggests that the use of IVF and PGD to achieve an unaffected child for patients with heritable retinoblastoma resulted in an overall cost-saving. There was an increase in QALYs per baby across all uptake rates. However, in total, fewer babies were born following the IVF and PGD pathway.

Live birth after in vitro maturation versus standard in vitro fertilisation for women with polycystic ovary syndrome: protocol for a non-inferiority randomised clinical trial

IntroductionPolycystic ovary syndrome (PCOS) is the first common cause of anovulatory infertility. Currently, in vitro fertilisation (IVF) is recommended when conventional attempts have failed. In vitro maturation (IVM) of human...

Predictive value of ovarian hormone-producing function assessment in poor responders undergoing assisted reproductive technologies

Hypothesis/aims of study. The management of poor responders to ovarian stimulation for in vitro fertilization (IVF) has always been a challenge. It is difficult for both doctors and patients to make decision to proceed to oocyte donation or abandon fertility treatment. More predictors of successful IVF treatment in poor responders are needed. The aim of this study was to assess hormonal ovarian function in poor responders undergoing ovarian stimulation and to identify predictors of the chance of clinical pregnancy after IVF cycle.&#x0D; Study design, materials and methods. The study included 45 infertile patients undergoing ovarian stimulation with poor ovarian response according to the Bologna criteria. All patients underwent standard IVF or IVF/ICSI protocol using gonadotropin releasing hormone antagonists. Letrozole (5 mg/day) was administered during the first 5 days of stimulation in standard antagonist FSH/hMG protocol to 13 of the patients included in the study, with standard antagonist FSH/hMG protocol being only administered to other 32 patients. Serum and follicular fluid were collected at the time of follicle aspiration, and the concentrations of total testosterone, estradiol and androstenedione were determined.&#x0D; Results. Follicular fluid concentrations of testosterone and androstenedione were higher and serum estradiol level was lower in the letrozole group. The serum concentrations of testosterone and androstenedione were comparable in both groups, while the serum estradiol/testosterone ratio was lower in the letrozole group. The threshold level of estradiol/testosterone ratio 1000 on the day of oocyte retrieval above which pregnancy and implantation rates were increased was 1532.68 (odds ratio 7.0 (95% CI 1.3935.35), р = 0.02).&#x0D; Conclusion. Evaluating of the serum estradiol / testosterone ratio has been shown to determine aromatase activity of ovarian preovulatory follicles and to predict IVF outcome in poor responders undergoing assisted reproductive technology.

Embryos derived from donor or patient oocytes are not different for in vitro fertilization outcomes when PGT allows euploid embryo selection: a retrospective study

BackgroundAt our facilities, patients that received embryos using donor oocyte during in vitro fertilization (IVF), usually have had at least one failed attempt to produce at least one euploid embryo with their own oocytes; however, the current debate between using donor over patient oocytes remains inconclusive. We examined the aneuploidy rate and IVF clinical outcomes from embryos derived from either donor or patient oocytes.MethodsRetrospectively, 973 cycles were examined of patients who underwent a standard IVF protocol. Chromosomal content was determined using Pre-implantation Genetic Testing (PGT) by either microarray-comparative genomic hybridization or Next-generation sequencing from either Day 3 (blastocysts) or Day 5 (trophectoderm) embryo biopsies, respectively. Embryo implantation was confirmed by serum β-hCG (> 10 m IU/mL/Day 14), whereas clinical pregnancy by a fetal heartbeat (Week 6.5–8).ResultsEmbryos derived from donor oocytes presented with more monosomies than embryos derived from patient oocytes (41.2% vs. 25.4%, p < 0.05, respectively); however, only Trisomy 7 (0.4% vs. 2.3%, p < 0.05) and Trisomy in X (0.7% vs. 2.3%, p < 0.05) were significantly less present when compared to patient oocyte derived embryos. Interestingly, rates for embryo implantation (46.7% vs. 50.8%, p = 0.35), clinical pregnancy (38.5% vs. 43.1%, p = 0.30), and live birth (30.5% vs. 30.5%, p = 0.99) were similar for embryos derived from donor and patient oocytes. These results did not change when adjusted for the number of embryos implanted.ConclusionHere, we show no significant differences in achieving pregnancy when using donor oocytes. Taking into consideration that aneuploidy rates are > 30% in embryos, independent of the oocyte origin, PGT should be recommended with donor oocytes as well.

Melatonin and Myoinositol: A Foreword Step Toward IVF Success, a Prospective Clinical Trial

Many subfertile couples, who failed to conceive naturally, seek help by means of artificial reproduction techniques such as in vitro fertilization (IVF) to achieve pregnancy. It is clear that oocyte and embryo quality depression are widely considered to be the main challenge of IVF in assisted reproduction. The aim of the study was to assess the effect and the role of melatonin combined with myoinositol on oocyte quality and to investigate its correlation with pregnancy outcome. A total of 315 patient, aged between 30-40, in a 12 month study period from Jan. 2017 to Dec. 2017, with history of one or multiple unsuccessful IVF cycles due to poor oocyte quality were included in this study. The study group (group 1, n=166) was treated with melatonin combined with myoinositol (Seidivid plus, SEIDLAB) for 3 months prior to a new IVF cycle and the control group (group 2, n =149) just received a standard IVF cycle without melatonin and myoinositol. IVF outcomes were compared between the two groups. Primary endpoint was the number of morphologically mature oocytes retrieved (MII oocytes). Secondary endpoints were fertilization rate per number of mature oocytes, embryo quality and pregnancy rate. After treatment, the number of mature oocytes, the fertilization rate, the number of top-quality embryos transferred and pregnancy rate were statistically higher compared to the previous IVF cycle, while there was no difference in the number of retrieved oocyte. The mean number of oocytes retrieved differ between the two groups being (11.56) in group 1 and (10.9) in control one (1920 vs. 1629) and the percentage of mature oocytes was significantly higher in melatonin-treated group (77.03% vs. 69.1%). Concurrently, the mean number of immature oocytes (germinal vesicles) was reduced (22.9% vs. 39.9%). Furthermore, the melatonin –myoinositol treated group showed an increase in fertilization rate (80.2% vs. 77.7%) and the mean number of grade one embryos resulted was also higher (60.05% vs. 49.5%). Clinical pregnancy rate was in tendency higher in the group treated with melatonin and myoinositol (48.3% vs. 40.8%), In the current study It was concluded that Melatonin and myoinositol treatment is likely to become a significant option for improving oocyte and embryo quality in women who cannot become pregnant because of poor oocyte quality.

In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction.

Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of reproductive age and 50% of women presenting with subfertility. Subfertility affects 15% to 20% of couples trying to conceive. A significant proportion of these women ultimately need assisted reproductive technology (ART). In vitro fertilisation (IVF) is one of the assisted reproduction techniques employed to raise the chances of achieving a pregnancy. For the standard IVF technique, stimulating follicle development and growth before oocyte retrieval is essential, for which a large number of different methods combining gonadotrophins with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist are used. In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response, characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome (OHSS). A potentially effective intervention for women with PCOS-related subfertility involves earlier retrieval of immature oocytes at the germinal-vesicle stage followed by in vitro maturation (IVM). So far, the only data available have derived from observational studies and non-randomised clinical trials. To assess the effectiveness and safety of IVM followed by IVF or ICSI versus conventional IVF or ICSI among women with PCOS undergoing assisted reproduction. This is the second update of this review. We performed the search on 17 April 2018.The search was designed with the help of the Cochrane Gynaecology and Fertility Group Information Specialist, for all published and unpublished randomised controlled trials (RCTs).We searched the the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL via the Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, and the trial registers for ongoing and registered trials and the Open Grey database for grey literature from Europe. We made further searches in the National Institute for Health and Care Excellence (NICE) fertility assessment and treatment guidelines. We handsearched reference lists of relevant systematic reviews and RCTs, together with PubMed and Google for any recent trials that have not yet been indexed in the major databases. All RCTs on the intention to perform IVM before IVF or ICSI compared with conventional IVF or ICSI for subfertile women with PCOS, irrespective of language and country of origin. Two review authors independently selected studies, assessed risk of bias, extracted data from studies, and attempted to contact the authors of studies for which data were missing. Our primary outcomes were live birth per woman randomised and miscarriage. We performed statistical analysis using Review Manager 5. We assessed evidence quality using GRADE methods. We found two RCTs suitable for inclusion in the review and six ongoing trials that have not yet reported results. Both included studies were published as abstracts in international conferences.Both studies were at unclear or high risk of bias for most of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.There were no data on the primary outcomes of this review, namely live birth per woman randomised and miscarriage.Both studies reported clinical pregnancy rate: there was evidence of an effect between IVM and IVF, favouring the former (odds ratio 3.10, 95% confidence interval 1.06 to 9.00; 71 participants; 2 studies; I2 = 0%; very low-quality evidence). The incidence of OHSS was zero in both studies in both groups.There were no data for the other outcomes specified in this review. Though promising data on the in vitro maturation (IVM) technique have been published, unfortunately there is still no evidence from properly conducted randomised controlled trials upon which to base any practice recommendations regarding IVM before in vitro fertilisation (IVF) or intracytoplasmic sperm injection for women with polycystic ovarian syndrome. Regarding our secondary outcomes, very low-quality evidence showed that clinical pregnancy was higher with IVM when compared to IVF, whereas the incidence of ovarian hyperstimulation syndrome was zero in both studies in both groups. We are awaiting the results of six ongoing trials and eagerly anticipate further evidence from good-quality trials in the field.