Embryo Transfer Research Articles

“Try until the last?”—the relevance of fresh embryo transfer outcomes for subsequent same-cohort vitrified–warmed cycles

PurposeTaking into consideration earlier attempts at assisted reproduction and previous pregnancies allows a more differentiated approach when counseling couples regarding their chances in assisted reproductive treatments. The aim of this study was to investigate whether the outcome of fresh embryo transfers affects subsequent same-cohort vitrified–warmed cycles.MethodsThis retrospective cohort study analyzes the outcome of all fresh and frozen embryo transfers (n = 8118) between January 1, 2011, and December 31, 2022. All women who received fresh or frozen embryo transfers at Kepler University Hospital Linz were included. The use of donor eggs, previously cryopreserved oocytes, and freeze-all cycles were excluded from the analysis.ResultsPositive serum βhCG after a fresh cycle has a significant impact on the chances of positive βhCG in a subsequent vitrified–warmed cycle (36.3% [33.2%, 39.5%]; P = 0.002). Negative βhCG after a fresh cycle does not predict the outcome of the following same-cohort embryo transfer (33.1% [30.7%, 35.7%], P = 0.726). Pregnancy rates of the first, second, third, and fourth same-cohort vitrified–warmed embryo transfer remain continuously high, with 32.8%, 30.8%, 28.9%, and 27.1%, respectively.ConclusionsPositive serum βhCG after a fresh embryo transfer has a positive predictive value for the outcome of a subsequent vitrified–warmed embryo transfer. Couples with a negative fresh cycle should not be discouraged from continuing fertility treatment using same-cohort frozen embryos.Trial registrationThis study was prospectively registered at the German Clinical Trials Register on September 5, 2023 (DRKS00032552).

Effect of blastomere cell number on ART outcome of fresh single day 3 embryo transfer

PurposeExplore the effect of blastomere cell number on ART outcome of fresh embryo transfer on day 3.MethodsRetrospective analysis of 540 fresh single day 3 embryo transfer cycles at the Reproductive Center of the Third Affiliated Hospital of Guangzhou Medical University from January 1, 2018 to October 31, 2022. Patients were divided into 5–6 cell group (n = 55), 7–9 cell group (n = 457), and ≥ 10 cell group(n = 28) based on the number of blastomeres. Single factor analysis of variance and Pearson's chi square test were used to compare the basic data, cycle information, pregnancy outcome and neonatal outcome. Univariate logistic regression was used to correct for confounding factors and analyze the influencing factors of pregnancy outcome.ResultsThe positive HCG rate were 20%, 43%, 25% for the 5–6-cell, 7–9 cell and ≥ 10 cell groups respectively, with statistically significant differences (P < 0.001). The clinical pregnancy rate was 18%, 42%,21%, respectively (P < 0.001). The live birth rates were 13%, 34%,21% with P-value less than 0.05 which is statistically significant. In order to exclude the influence of confounding factors, multivariable logistic regression analysis was performed, and the outcomes were consistent with previous findings. There were no significant differences found in neonatal outcome between groups (P > 0.05).ConclusionThe results suggested that intermediate cleaving embryos (7–9 cell) still presents the highest clinical potential. Fast and slow cleaving embryos are not conducive to the ART outcome.

Recurrent pain after laparoscopic surgery for ovarian endometrioma: Clinical features and long-term follow up

PurposeWe aimed to examine the clinical characteristics of patients with ovarian endometriosis (OMA) who were diagnosed with recurrent pain after laparoscopic surgery in an 8- to 12- year postoperative follow-up. MethodsWe retrospectively analyzed data of 45 OMA patients with recurrent pain, including a minimum 8 years of post-laparoscopic follow-up reports. All laparoscopic cystectomy procedures were performed by the same surgeon at Peking Union Medical College Hospital between January 2009 and April 2013. Clinical data were retrieved to analyze patients' preoperative characteristics, relevant surgical findings, and postoperative outcomes at follow-up. ResultsA total of 45 patients with OMA were included, with a mean age of 31.8±4.92 years. The mean recurrence period was 45.78±24.89 months. Before surgery, 60% (27/45) of patients had severe dysmenorrhea. During surgery, 93.3% (42/45) of patients were in stage III/IV, 51.1% (23/45) had coexisting adenomyosis, and 66.7% (30/45) had deep infiltrating endometriosis (DIE). For the whole study group, mean follow-up time was 121.96±15.55 months. All patients underwent postoperative medical treatment. The mean recurrence period was 45.78±24.89 months. Cyst recurrence was presented in 24.4% (11/45) of patients, while 75.6% (34/45) only complained of pain recurrence. At the end of follow-up, spontaneous pregnancy was seen in 24.4% (11/45) of patients and 6.7% (3/45) received in vitro fertilization and embryo transfer (IVF-ET). ConclusionsPatients with symptomatic recurrence after surgery had more severe dysmenorrhea, larger proportion of coexisting adenomyosis and DIE, and a higher revised American Fertility Society (rAFS) stage. Recurrence of endometrial cysts was not related to pain recurrence. Long-term postoperative pharmacological therapy is recommended to reduce recurrence.

The influence of trophectoderm biopsy for preimplantation genetic testing in the serum level of first trimester biomarkers: PAPP-a, βhCG and PIGF

Research questionDoes trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A) affect maternal serum first trimester pregnancy biomarkers (PAPP- A, free β-hCG, PlGF)? DesignRetrospective cohort study, including all singleton pregnancies (n=9794) following either spontaneous conceived (SC) (n=8005) in vitro fertilization and fresh embryo transfers (IVF) (n=478) or frozen embryo transfer of non PGT-A (FET)(n=963) or PGT-A tested embryos (FET+PGT-A) (n=348). In all women with a viable pregnancy at 8-13.6 weeks of pregnancy, we measured serum levels of free β-hCG and PAPP-A . PlGF was measured in 3784 patients. These biomarkers were converted to a multiple of the expected normal median (MoM) for a pregnancy of the same gestational day. We calculated the medians for the multiple of the median and compared them. ResultsFree β-hCG did not differ according to the mode of conception. PAPP-A concentrations were significantly lower in in vitro fertilization and fresh embryo transfers (-0,1 Log10 MoM raw PAPP-A) when comparing to FET+PGT-A (-0,04 Log 10 MoM raw PAPP-A) and SC (-0,0187 Log 10 MoM raw PAPP-A) (p<0,05). PlGF levels were significantly lower in the FET+PGTA group (p<0.05). The difference in means adjusted by CRL was 4.6 pg/ml 95%CI [2.7-6.6] for SC, 3.5 pg/ml 95%CI [0.34-6.6] for IVF and 2.2 pg/ml 95%CI [0.06-4.4] for FET. ConclusionThis study demonstrates that trophectoderm biopsy for PGT-A has a significant impact on first trimester maternal serum PAPP-A and PIGF. This needs to be further validated since it may mislead the estimation of the first trimester risk of aneuploidies and preeclampsia.

Impact of Different Progesterone Timings on Live Birth Rates for Blastocyst Frozen Embryo Transfer Cycles

(Abstracted from Reprod Biomed Online 2024;49(4):104307) Assisted reproductive technology use has been increasing exponentially within the last few decades, with frozen embryo transfer (FET) cycles among them. In preparation for an FET cycle, patients can undergo a natural cycle or an artificial cycle designed to simulate a natural cycle with exogenous estrogen and progesterone.

Effect of hysteroscopic surgery on IVF/ICSI pregnancy outcomes for different cesarean scar diverticulum severity: A retrospective cohort study.

To investigate associations between hysteroscopic surgery for patients with varying cesarean scar diverticulum (CSD) severity and invitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) pregnancy outcomes, focusing also on the correlation between the CSD size with its severity, and pregnancy outcomes. A retrospective study was conducted on patients with CSD who underwent IVF/ICSI-ET at a university-based hospital between January 2017 and July 2023. Patients were categorized into four groups based on CSD severity and whether they received hysteroscopic surgery: a mild surgical group (Group A, n = 86), a mild non-surgical group (Group B, n = 30), a moderate-to-severe surgical group (Group C, n = 173), and a moderate-to-severe non-surgical group (Group D, n = 96). Baseline characteristics and pregnancy outcomes were compared among these groups. Correlation assessments were conducted to explore relationships between CSD size with its severity, and pregnancy outcomes. Compared with Group D, Group C exhibited significantly increased rates of biochemical pregnancy (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.03-3.51, P = 0.041), clinical pregnancy (OR 2.30; 95% CI1.18-4.45; P = 0.014), and live birth (OR 2.77; 95% CI 1.10-7.00, P = 0.031). However, no differences in pregnancy outcomes were observed between Groups A and B. Correlation analyses revealed significant positive associations between CSD severity and its depth, length, width, and volume. Patients with moderate-to-severe CSD achieved favorable IVF/ICSI pregnancy outcomes following hysteroscopic surgery. The CSD size was significantly related to its severity.

Revival of an efficient patient and operator friendly embryo transfer technique: UMbET (ultrasound measurement before embryo transfer)

Revival of an efficient patient and operator friendly embryo transfer technique: UMbET (ultrasound measurement before embryo transfer)

Feasibility of preimplantation genetic testing for aneuploidy on frozen-thawed embryos following conventional IVF insemination.

Intracytoplasmic sperm injection (ICSI) is commonly employed in preimplantation genetic testing (PGT) to minimize the risk of foreign sperm DNA contamination. Cryopreserved embryos from patients with recurrent miscarriage or repeated implantation failure, who have undergone conventional in vitro fertilization (IVF), can be thawed and biopsied for PGT. Therefore, we aimed to assess the accuracy and effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) on frozen embryos using conventional IVF (c-IVF) insemination methods. From January 2021 to November 2023, our center conducted 107 thawed cryopreserved embryo biopsy cycles to screen for PGT-A. Among them, 58 cycles used c-IVF insemination, and 49 used ICSI insemination. Basic patient clinical information, laboratory data, PGT test results, and clinical outcome data were collected. To minimize the confounding effects of patient characteristics and embryo quality on PGT-A outcomes, clinical outcomes, and contamination assessment, these variables were included in the analysis. We then evaluated the blastocyst euploidy rate, clinical outcomes, and accuracy of PGT-A results between the two groups and analyzed potential contamination in the c-IVF insemination group. A total of 320 blastocysts underwent PGT-A testing, with 179 blastocysts from c-IVF insemination and 141 from ICSI insemination. Considering participants' baseline characteristics and embryological outcomes, no significant differences were found between the two groups regarding infertility type, average age, body mass index, percentage of PGT-A indications, or quality of embryonic development. Regarding PGT-A results, all 320 biopsy samples were successfully analyzed, showing no statistical variance in chromosomal euploidy, abnormality, or mosaicism rates between the two insemination methods. No parental contamination was detected in the c-IVF insemination group. When assessing clinical outcomes, parameters such as biochemical pregnancy, clinical pregnancy, and miscarriage rates did not exhibit significant discrepancies between the two groups, and no misdiagnoses were reported during the study period. Embryo transfer and PGT-A results are not affected by potential parental contamination in frozen-thawed embryos conceived via c-IVF. PGT-A guided embryo transfer in thawed embryos conceived by c-IVF is a viable and clinically effective approach.

Progestin-primed ovarian stimulation

The use of progestins for the prevention of premature ovulation during ovarian stimulation is called progestin-primed ovarian stimulation (PPOS). Response to ovarian stimulation with PPOS and gonadotropin-releasing hormone (GnRH) analogs seem to be similar with the clinically insignificant differences being explained by endocrine characteristics as expected. PPOS has the advantage of oral administration and lower medication cost than GnRH analogs, but the mandatory cancellation of an otherwise possible fresh embryo transfer can render PPOS less cost-effective if a fresh transfer would have been possible. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analog cycles seem similar both in terms of ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies reported lower cumulative live birth rates with PPOS, they suffer from methodological issues, including arbitrary definitions of cumulative live birth rates. PPOS has been used in all patient types with consistent results and seems a patient-friendly and cost-effective choice when a fresh embryo transfer is not intended.

Why choose the rabbit to work in reproductive technology?

Rabbits have played a significant role in both livestock production and the advancement of reproductive scientific research. Their unique biological traits, including induced ovulation and a reproductive process that closely mirrors that of humans, have been pivotal in their use as a model. Moreover, their body size is perfectly aligned with the 3Rs principles: Replacement, Reduction, and Refinement. Consequently, techniques for gamete collection and embryo recovery, followed by their use in artificial insemination or embryo transfer, are characterized by being minimally invasive. However, refining invitro fertilization and embryo culture techniques continues to present challenges. The incorporation of cutting-edge genomic editing tools, such as CRISPR/Cas9, has reestablished rabbits as essential models in genetic and biomedical research, driving scientific progress. This review aims to describe the most effective reproductive biotechnologies for both male and female rabbits and how these methodologies are in line with the 3Rs principles-Replacement, Reduction, and Refinement-highlighting their significance in conducting ethical research.

Advanced assisted reproduction technologies in endangered mammalian species.

A new synergistic approach of classical conservation strategies combined with advanced assisted reproduction technologies (aART) allows for protection and rescue of endangered keystone species at the brink of extinction, which can help to safeguard complex ecosystems. Reproduction biology and management in mammal species is not only challenging in regards to their diverging sizes, anatomy, and often unknown physiology; it also requires customized training or chemical restraint protocols for safe handling. Besides these general challenges, there are several new assisted reproduction techniques (ART) specifically tailored to critically endangered mammals. The current portfolio of ART in these mammalian taxa is ranging from sexual cycle characterization and manipulation, semen collection and cryopreservation, artificial insemination, biobanking of living cells, oocyte collection, invitro fertilization (IVF), and embryo production, embryo transfer as well as stem cell-derived invitro gametogenesis for generating gametes in culture. The article covers advanced assisted reproduction technologies (aART), success and challenges, as well as ethical implications.

Perinatal Outcomes of Women with Recurrent Pregnancy Loss Undergoing Frozen Embryo Transfer from the Society of Assisted Reproductive Technology Database

To assess whether infants born to women with a history of recurrent pregnancy loss (RPL) have an increased risk of adverse perinatal outcomes following frozen embryo transfer (FET) compared to women without a history of infertility or RPL. Retrospective cohort study utilizing the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) database between 2014 and 2020. Patients in the SART CORS database who underwent their first FET resulting in live birth either with a diagnosis of RPL (cases n=3,299) or without a history of RPL or infertility, the comparison population being tubal ligation (TL) only (n=1408). Recurrent pregnancy loss MAIN OUTCOME: Low birthweight (<2500g), additional outcomes included gestational age (continuous), birthweight (continuous), preterm delivery (< 37 weeks), mode of delivery, and neonatal death, defined as death prior to the completion of the 28th day of life. We observed no statistically significant difference in low birthweight, birthweight overall, mode of delivery or risk of neonatal death between patients with RPL compared to women with tubal ligation who underwent their first FET resulting in live birth. Patients with history of RPL compared to TL utilizing FET were more likely to have a later gestational age at delivery (p<0.001). Patients with RPL were also less likely to have a preterm delivery (imputed AOR 0.75 [0.64, 0.89]) than the TL patients. Furthermore, performing preimplantation genetic testing for aneuploidy (PGTA) in both patients with recurrent pregnancy loss or tubal ligation did not impact perinatal outcomes compared to patients who did not undergo PGTA. Patients with history of recurrent pregnancy loss do not have an increased risk of adverse perinatal outcomes when they undergo FET compared to patients without infertility or recurrent pregnancy loss. In addition, performing IVF/PGTA in patients with RPL does not adversely impact birth outcomes of their infants.

Methodological approaches in vitrification: Enhancing viability of bovine oocytes and invitro-produced embryos.

Cryopreservation of bovine oocytes and embryos is essential for long-term preservation and widespread distribution of genetic material, particularly in bovine invitro embryo production, which has witnessed substantial growth in the past decade due to advancements in reproductive biotechnologies. Among current cryopreservation methods, vitrification has emerged as the preferred cryopreservation technique over slow freezing for preserving oocytes and invitro-produced (IVP) embryos, as it effectively addresses membrane chilling injury and ice crystal formation. Nonetheless, challenges remain and a simple and robust vitrification protocol that guarantees the efficiency and viability after warming has not yet been developed. Furthermore, although slow cooling can easily be adapted for direct transfer, an easier and more practical vitrification protocol for IVP embryos is required to allow the transfer of IVP embryos on farms using in-straw dilution. In addition, the susceptibility of bovine oocytes and embryos to cryoinjuries highlights the need for novel strategies to improve their cryotolerance. This manuscript examines various methodological approaches for increasing the viability of bovine oocytes and IVP embryos during vitrification. Strategies such as modifying lipid content or mitigating oxidative damage have shown promise in improving cryotolerance. Additionally, mathematical modelling of oocyte and embryo membrane permeability has facilitated the rational design of cryopreservation protocols, optimizing the exposure time and concentration of cryoprotectants to reduce cytotoxicity.

Uncovering the association between embryo development and early pregnancy loss using artificial intelligence annotated kinetic events

Research questionCan artificial intelligence powered annotation of numerous biological events help uncover an association between embryonic kinetics and early pregnancy loss? DesignA multicentric retrospective analysis was conducted on 37717 embryos (7028 egg retrievals, 13 centers in France and Spain, three different time-lapse systems). The videos of developing embryos were analyzed with artificial intelligence to detect developmental events, including t2, t5, t8 (cleavage from 2 cells to 8 cells), tSB (start blastulation) and tB (blastocyst). The association between embryo kinetics and transfer outcome (lack of early pregnancy, early pregnancy loss and clinical pregnancy) was investigated using univariate and multivariate logistic regressions. ResultsAn optimal kinetics for clinical pregnancy was identified as being statistically different from that of embryos which led to an early pregnancy loss (p<0.01). As much as overall faster developing embryos (tB-t2=77.18±8.33 hours) were the most likely to lead to an early pregnancy, it appeared that beyond early pregnancy, embryos that showed a deceleration during cleavage (tsB-t5=46.05±13.60 hours) followed by a subsequent acceleration during blastulation (tB-tSB=9.81±5.04 hours) were the most likely to lead to clinical pregnancy. Conversely, embryos that presented the fastest cleavage and longest blastulation kinetics were the most likely to lead to an early pregnancy loss. ConclusionsAnalyzing numerous kinetic combinations annotated with artificial intelligence reveals patterns which can help distinguish embryos that are competent enough for early pregnancy but not for clinical pregnancy. Detecting such subtle kinetic differences could add transparency to algorithms by pinpointing which phases of an embryo development might be predictive of a pregnancy loss.

Reassessing the conventional fertilisation check: leveraging PGT-A to increase the number of transferrable embryos

Reassessing the conventional fertilisation check: leveraging PGT-A to increase the number of transferrable embryos

Case 330: Ovarian Torsion in the Setting of Ovarian Hyperstimulation Syndrome.

A 30-year-old female patient with a history of infertility and no pregnancy presented to the gynecologic endometriosis clinic for follow-up 1 month after oocyte retrieval, to be evaluated for pelvic optimization before potential embryo transfer, with worsening dysmenorrhea, dyspareunia, and overall pelvic pain. Eleven years prior, the patient had undergone left ovarian cystectomy for treatment of endometrioma, as well as excision of deep infiltrating endometriosis. The oocyte retrieval procedure, where more than 30 eggs were retrieved, was complicated by ovarian hyperstimulation syndrome and intraperitoneal bleeding, which necessitated admission to the intensive care unit (ICU) for 3 days. Following discharge from the ICU, the patient experienced occasional on-and-off pressure of the urinary bladder and persistent aching pelvic pain.

Legal framework and IVF outcomes: a comparative analysis of fresh and frozen embryo transfers in Switzerland

Research question: To what extent do legislative measures impact standard reproductive outcome parameters? Design: Retrospective cohort study using data from the Swiss national IVF registry analysing the outcomes of 13908 women undergoing ETs resulting from their first lifetime oocyte retrieval before (2014-2016) or after (2020-2022) the revised legislation, allowing extended culture for 12 zygotes. Live birth rates (LBR) and cumulative LBR (cLBR) were compared in fresh and frozen ET strategies in both periods. Adjusted multivariable mixed model analyses were performed to determine odds ratios (OR) and incidence rate ratios (IRR). ResultsBefore the revised legislation, LBR was higher in fresh compared to frozen ET (27.2% vs. 22.7%). After the revised legislation, LBR was lower in fresh ET (29.3% vs. 36.3%) and cLBR was higher in freeze-all strategy (cLBR: 59.0% vs. 39.8%). However, in a multivariable analysis, fresh and frozen ETs did not differ in the odds of live birth (OR = 1.08, 95% CI: 0.95-1.22) and freeze-all were not found to be more effective than fresh strategies (IRR = 1.12, 95% CI 0.98 - 1.27). In a subgroup analysis, fresh blastocyst ET showed higher LBR than cleavage stage ET (OR = 2.01, 95% CI 1.62-2.49). ConclusionThe change in national legislation provided the unique opportunity to evaluate the legal impact on reproductive outcomes: Besides a reduction of multiple deliveries, LBR of frozen ET improved, resulting in a comparable success of fresh and frozen transfer strategies. In addition to technological improvement, the legal framework influences the evolution of clinical practice, thereby contributing to enhanced reproductive outcomes.

Enhancing uterine receptivity for embryo implantation through controlled collagenase intervention.

Ineffective endometrial matrix remodeling, a key factor in infertility, impedes embryo implantation in the uterine wall. Our study reveals the cellular and molecular impact of human collagenase-1 administration in mouse uteri, demonstrating enhanced embryo implantation rates. Collagenase-1 promotes remodeling of the endometrial ECM, degrading collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors (e.g., VEGF, decorin), facilitating vascular permeability and angiogenesis. Collagenase-1 elevates embryo implantation regulators, including NK cell infiltration and the key cytokine LIF. Remarkably, uterine tissue maintains structural integrity despite reduced endometrial collagen fiber tension. In-utero collagenase-1 application rescues implantation in heat stress and embryo transfer models, known for low implantation rates. Importantly, ex vivo exposure of human uterine tissue to collagenase-1 induces collagen de-tensioning and VEGF release, mirroring remodeling observed in mice. Our research highlights the potential of collagenases to induce and orchestrate cellular and molecular processes enhancing uterine receptivity for effective embryo implantation. This innovative approach underscores ECM remodeling mechanisms critical for embryo implantation.

Birth weight following frozen versus fresh embryo transfer: A retrospective cohort

Birth weight following frozen versus fresh embryo transfer: A retrospective cohort

Differences in perinatal complications and serum hormone levels due to uterine endometrial preparation methods in frozen-thawed embryo transfer.

In frozen-thawed embryo transfer (FET), differences in endometrial preparation methods affect the incidence of perinatal complications. However, the underlying causes are unclear. We aimed to investigate whether serum E2, P4 levels are associated with perinatal complications. This is a retrospective cohort study, involving 306 successful FET pregnancies from 2017 to 2022. Participants were divided into Natural Cycle (NC) and Hormone Replacement Cycle (HRC) group. We compared serum hormone levels, maternal backgrounds, and perinatal outcomes and complications. Furthermore, within the HRC group, serum hormone levels were compared for perinatal complications previously reported to show differences in incidence rates depending on the method of endometrial preparation. HRC exhibited significantly higher serum E2 levels during the implantation period, but lower P4 levels during ovulation, implantation, and pregnancy test period compared with NC. HRC also had significantly higher rates of postpartum hemorrhage (PPH) and placenta accreta spectrum (PAS). There was no association found between perinatal complications more likely to occur in HRC and serum E2, P4 levels. In HRC, there were more occurrences of PPH and PAS. Although serum E2, P4 levels during FET did not correlate with perinatal complications.