bluuebunny/crossref_metadata_2025 huggingface dataset:
O-292 Does ovulation trigger enhance live birth in a natural cycle for frozen embryo transfer: A randomized controlled trial
Authors: Huberlant S , Ranisavljevic N , Bonneau M , Rougier N , Serand C , Anahory T , Hamamah S
Published: June 2023

Study question

Does ovulation trigger enhance pregnancy rate in a natural cycle (NC) for frozen embryo transfer (FET)?

Summary answer

Pregnancy rates after a FET are similar in a natural cycle with detection of a spontaneous LH surge or with a triggered ovulation.

What is known already

Several studies have explored whether one approach might appear to be more beneficial in terms of pregnancy or live birth rates, but with inconsistent results. Thus, the best protocol to identify the time of ovulation in NC and to plan the FET is still undefined.

Study design, size, duration

This was a bicentric, two-arm, randomized, controlled and open-label trial, including 108 patients for 18 months. In the spontaneous-NC group, the LH surge was defined as a rise of the serum LH level at least three times above the basal LH serum value with a serum progesterone level three days after the LH surge above 3 ng/mL.

Participants/materials, setting, methods

Patients included were aged 18- to 39-year-old, had regular cycles and were planned for an autologous frozen day-5 blastocyst transfer in a NC. They did not have endometriosis stage AFSr 3 nor 4 nor adenomyosis. Fifty-four patients per group were included. In the modified-NC group, a spontaneous LH surge was observed in 16 women before the hCG-trigger could be administrated: they were re-allocated to the spontaneous-NC for the per-protocol (PP) analysis.

Main results and the role of chance

Patients characteristics were comparable in both groups. Pregnancy rates were similar in the spontaneous-NC and the modified-NC group in the intention-to-treat (ITT) (41.3 versus 37.8% respectively, p = 0.85) and in the PP analysis (39.3% versus 40% respectively, p = 0.9). Ongoing pregnancy, miscarriage and live birth rates were also similar. Significantly more visits were needed in the spontaneous-NC (3.4 ± 0.81 versus 2.59 ± 1.0, p < 0.0001 in the ITT analysis and 3.18 ± 0.93 versus 2.63 ± 1.03, p = 0.0064 in the PP analysis).

Limitations, reasons for caution

Due to group redistribution (spontaneous LH surge before hCG trigger), the number of subjects in the modified-NC group is low for the PP analysis. This may reduce the power of the trial which may fail to detect a small difference.

Wider implications of the findings

The results reinforce previous data that showed similar efficacy of the s-NC and the m-NC. This allows the patient to choose from several options depending on her preference.

Trial registration number

NCT03428165
O-301 Can advanced sperm selection techniques improve blastocyst euploidy rate of abnormal sperm DNA fragmentation cases to the level of normal ones; prospective randomized controlled trial
Authors: Hasanen E , Hozayen M , Elshimy A , Hazem Y , Alkhader H , Zaki H
Published: June 2023

Study question

To compare PGT-A outcomes of Physiological ICSI (PICSI) and magnetic activated cell sorting (MACS) sperm selection techniques to a control of normal sperm DNA fragmentation.

Summary answer

PGT-A outcomes did not differ between using normal sperm DNA fragmentation semen to the semen processed by PICSI or MACS.

What is known already

Sperm DNA fragmentation can negatively affects pre-implantation embryo development in all stages after ICSI. Advanced sperm selection techniques like PICSI and MACS are thought to be efficient to improve fertilization, cleavage, and blastocyst formation rates in cases with abnormal SDF. It has become evident that a blastocyst's aneuploidy is not only contributed by the oocyte,but can also be caused by the sperm.The relation between sperm selection techniques such as PICSI or MACS and blastocyst euploidy is not investigated yet.

Study design, size, duration

A prospective randomized controlled trial of 351 ICSI cycles in a private fertility center, from October 2019 to December 2022. Cases were included in the study if: female had ≥5 MII oocytes, male had abnormal sperm DNA fragmentation (SDF) index (>20% by TUNEL assay), all blastocysts (≥4BB) had trophoectoderm biopsy.

Participants/materials, setting, methods

Included cases were randomized on the day of ICSI to PICSI or MACS group, along with a control arm of cases with normal SDF needed for comparison. PGT-A was done using Illumina platform (Miseq), and the results were reviewed by artificial intelligence (Cooper Surgical). Cases were categorized according to the female age into 2 subgroups(<35, and > 35 years). Statistical analysis of all pre-implantation embryo development parameters and PGT-A results were done using SPSS.

Main results and the role of chance

We found no significant differences between the female age, male age, count, motility, SDF, no. mature oocytes between the studied groups.

Limitations, reasons for caution

The results included all pre-implantation embryo parameters but, subsequent post-implantation events like implantation, pregnancy and miscarriage rates will add more data about the competency of the resulted embryos.

Wider implications of the findings

The usage of advanced sperm selection techniques like PICSI or MACS has showed comparable results to that of normal SDF cases, through eliminating the adverse effects of SDF on ICSI and PGT-A outcomes.

Trial registration number

NCT05494216
P-004 Sperm concentration of less than 1 million/ml in Y microdeletion patients may affect ICSI clinical outcomes: a propensity score matching analysis
Authors: Zhang H
Published: June 2023

Study question

To investigate which semen parameter in AZFc microdeletion patients affect the intracytoplasmic sperm injection (ICSI) clinical outcomes.

Summary answer

AZF-microdeletion caused oligospermia affected the ICSI clinical outcome when the sperm concentration is less than 1x106/ml.

What is known already

To reduce the impact of female factors on clinical outcomes, this study employed a propensity score matching analysis to retrospectively analyze the laboratory and clinical pregnancy results of patients with AZFc deletion who underwent ICSI.

Study design, size, duration

A propensity score matching analysis in a retrospective ICSI cohort of 99 AZFc microdeletion patients and 198 oligospermia patients without AZFc microdeletion.

Participants/materials, setting, methods

Patients/Animals: oligospermia patients with or without AZFc microdeletion undergoing ICSI.

Intervention: ICSI for couples attempting conception.

Main Outcome Measures: Outcomes included normal fertilization rate, high-quality embryo rate on Day 3, clinical pregnancy rate, abortion rate, and live birth rate.

Main results and the role of chance

Patients with AZFc microdeletion had a lower normal fertilization rate (69.55%) and Day-3 high-quality embryo rate (50.73%) than the control group (77.17% and 58.44% respectively, p = 0.000). There was no significant difference between the two groups in the clinical pregnancy rate (67.21% vs. 68.16%, p > 0.05), miscarriage rate (13.41% vs. 12.54%, p > 0.05), and live birth rate (58.20% vs. 59.18%, p > 0.05). Subgroup analysis showed that the fertilization rate, high-quality embryo rate, clinical pregnancy rate, and live birth rate were comparable between the AZFc-microdeletion group and the control groups when the sperm concentration was no less than 106/ml. Interestingly, when the sperm concentration was below 1x106/ml, the fertilization rate (65.60% vs. 73.79%, p = 0.001) and high-quality embryo rate (47.74% vs. 58.48%, p = 0.001) in the AZFc-microdeletion group were significantly lower than those in the control group. Furthermore, the clinical pregnancy rate and live birth rate were lower, while the miscarriage rate was higher in the AZFc-microdeletion group; however, the statistical difference is not significant.

Limitations, reasons for caution

the retrospective study was limited, and the cases of obtaining testicular sperm by microsurgery were not included, so the results may be biased, and prospective studies with larger sample size need to be designed for further confirmation.

Wider implications of the findings

We recommend screening for AZF in Chinese male infertile population when sperm concentration is below 5X106/ml.The male physician should advise the patient to undergo genetic counseling before pregnancy assistance, and choose whether to choose PGT assisted pregnancy according to the patient's wishes.

Trial registration number

not applicable
P-031 Presence of HPV 16 and HPV 18 in spermatozoa and embryos of mice
Authors: Mastora E , Zikopoulos A , Evangelou T , Georgiou I , Zikopoulos K
Published: June 2023

Study question

The clarification of Human Pappiloma Virus (HPV) internalization in spermatozoa and early preimplantation embryos.

Summary answer

Spermatozoa are able to internalize constructs of cloned high risk HPV viruses either as integrated or as episomal DNA.

What is known already

Human Pappiloma Virus (HPV) is a non-enveloped, circular, double stranded DNA virus. Persistent infection with oncogenic HPV genotypes triggers HPV DNA integration into the host genome, eventually leading to chromosomal damage accumulation and genome destabilization in infected cells. Living spermatozoa of almost all species are able to take up spontaneously exogenous DNA and internalize a part of it into their nucleus.

Study design, size, duration

Taking into account the capability of sperm cells to integrate exogenous DNA into their genome, we sought to clarify HPV internalization into sperm genome. A total of 26 sperm samples were studied. The control group included 97 embryos. As for the HPV 16 and HPV 18 group, a total of 89 embryos were studied.

Participants/materials, setting, methods

Sperm was incubated with plasmid vectors containing the complete genome of human HPV 16 and HPV 18 tagged with the green fluorescent protein (GFP) gene, to investigate HPV 16 and HPV 18 integration in mouse spermatozoa. Oocytes were in vitro fertilized with preincubated spermatozoa to investigate HPV 16 and HPV 18 potential transfer to mouse embryos.

Main results and the role of chance

Spermatozoa were able to internalize constructs of cloned high-risk HPV either as integrated or as episomal DNA. Constructs of cloned HPV can also be transferred to mouse embryos, through in vitro fertilization of the oocytes by mouse spermatozoa.

Limitations, reasons for caution

Viral DNA integration into the sperm nucleus could not be directly demonstrated, but nevertheless integration is evident by GFP gene expression.

Wider implications of the findings

This study highlights the possibility of viral DNA transmission to the early embryo via sperm, opening new perspectives on the effect of HPV in reproductive cells. HPV persistence may impair sperm parameters, suggesting caution in the use of these cells for assisted reproduction techniques or sperm banking.

Trial registration number

Not applicable
P-076 Sperm selection by thermotaxis: a novel technique to enhance assisted reproductive technologies’ outcomes
Authors: Guleresi K , Santos Ribeiro S , Reis Soares S , Nunes Gouveia S , Gómez Alves S
Published: June 2023

Study question

Does sperm selection by thermotaxis increase competent spermatozoa count?

Summary answer

When compared to capacitation alone, our findings suggest an improvement in the availability of high quality spermatozoa after thermotaxis in terms of motility and morphology.

What is known already

Thermotaxis is a natural mechanism that guides competent spermatozoa through the female genital tract. It has been previously shown that, in the mice model, thermotaxis may improve pregnancy rates following in vitro fertilization (IVF). However, thus far, there is little information to support these findings with human spermatozoa.

Study design, size, duration

A prospective single-center paired pilot analysis was performed between April 2021 and April 2022 including 21 male individuals, 12 of whom were sperm donors and 9 who were patients with asthenozoospermia (defined as < 32% progressive sperm motility).

Participants/materials, setting, methods

Only otherwise healthy men between 18 and 45 years old were included. All subjects performed a sperm collection at the clinic after a maximum of 3 days following the last ejaculation. Sperm concentration, motility, morphology (all using the WHO 2010 criteria) and DNA fragmentation (TUNEL) were assessed within the same sample at three time-points: fresh sample, after capacitation and following the extra thermotaxis procedure.

Main results and the role of chance

The average age of the participants was 34.9 ± 6.6 years old. The mean sperm concentration was 66.9 ± 39.1 million/mL (91.4 ± 26.1 in the donor subset (group A) versus 34.2 ± 28.0 in the asthenozoospermia patient (group B) subgroup). The median sperm motility was 62.0% (66.5% in group A versus 24.0% in group B). The mean sperm morphology was 7.2% (7.7% in the group A versus 6.7% in the group B). When compared to the sample in which only capacitation was performed, a statistically significant increase in spermatozoa motility (52.10% vs 82.14%, p < 0.05) and normal morphology (11% vs 16%, p < 0.05) was observed following capacitation plus thermotaxis. Conversely, DNA fragmentation did not vary significantly within the capacitated samples before and after thermotaxis (13% vs 14%).

Limitations, reasons for caution

The present pilot study is based on a limited number of participants and should be extended further.

Wider implications of the findings

The combination improvement in terms of morphology and progressive motility following thermotaxis may optimize selection of sperm cells and ultimately increase pregnancy rates after IVF. In the light of our experience, it is possible that this technique, which does not require high-end equipment, may increase the usable competent spermatozoa count.

Trial registration number

NCT04849156
P-083 Associations of sperm epigenetic aging with semen parameters among men from the U.S. general population
Authors: Pilsner R , Sawant S , Houle E , Oladele O
Published: June 2023

Study question

Is sperm epigenetic aging (SEA) associated with semen parameters among men in the general population?

Summary answer

While SEA was not associated with general semen parameters, advanced SEA was positively associated with sperm head defects such as length, perimeter, and pyriforms.

What is known already

We have previously shown that advanced SEA was strongly associated with longer time-to-pregnancy among couples in the general population.

Study design, size, duration

A population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009.

Participants/materials, setting, methods

Sperm DNA methylation from 379 semen samples were assessed via Illumina EPIC Array and SEA was estimated using Super Learner, an ensemble machine learning algorithm. Linear regression models were employed to examine the associations between semen parameters and SEA adjusting for male age and current smoking.

Main results and the role of chance

None of the general semen characteristics such as count, concentration, motility or morphology were associated with SEA. However, several sperm head parameters were positively associated with SEA including length (β = 3.6, 95% confidence internal (CI): 1.01 - 6.23; p = 0.007); perimeter (β = 4.04, 95% CI: 0.1 – 0.05; p = 0.045) and pyriforms (β = 0.29, 95% CI: 0.1-0.49; p = 0.003). SEA was also inversely related to sperm elongation factor (β = -2.9, 95% CI: -4.8 - -1.1; p = 0.002).

Limitations, reasons for caution

This prospective cohort study consisted primarily of Caucasian men and women and thus large diverse cohorts are necessary to confirm the associations between SEA and sperm head defects in other races/ethnicities.

Wider implications of the findings

These data suggest that advanced sperm epigenetic aging may be related to improper sperm head condensation during spermatogenesis.

Trial registration number

N/A
P-232 Beyond 12 months, blastocyst cryostorage duration in close system affects live birth rate: a monocentric retrospective study
Authors: Yahyaoui A , Barry F , Anav M , Loup V , Mullet T , Anahory T , Brouillet S , Hamamah S
Published: June 2023

Study question

In order to evaluate the effect of blastocyst cryopreservation duration on live birth rate (LBR).

Summary answer

Blastocyst cryopreservation duration negatively affects live birth rate when blastocysts are vitrified in complete close system for more than 12 months.

What is known already

With the development of embryo vitrification, frozen-thawed program embryo transfer has been widely used in the past decade. However, the association between cryopreservation duration and frozen blastocyst transfer outcomes are limited. So far, very few studies have provided evidence on the relationship between blastocyst storage duration and LBR.

Study design, size, duration

This monocentric retrospective study included 1267 women (n = 1462 cycles) who underwent single frozen blastocyst transfer. Duration of vitrification in close system was categorized into five groups included 2144 frozen blastocysts (Day 5/6) : <3 months (n = 417; mean female age = 32.6 ± 4.74y), 3-6 months (n = 596; mean female age = 33.2 ± 4.96y), 6-12 months (n = 440; mean female age = 33.4 ± 4.83y), 12-36 months (n = 512; mean female age = 32.6 ± 4.75y), and >36 months (n = 179; mean female age = 31.1 ± 3.90y).

Participants/materials, setting, methods

Clinical pregnancy and live birth outcomes were compared between the cohorts stratified according to blastocyst cryostorage duration. A binary multivariate logistic regression was performed, adjusting for confounders: female age at vitrification, male age, ART technique (IVF or ICSI) and endometrial preparation protocol (spontaneous, substituted and stimulated FET cycle).

Multivariable analysis was used to assess the association between crystorage duration of vitrified blastocyst and LBR. All frozen blastocyst transfers were realized in spontaneous, substituted or stimulated cycles.

Main results and the role of chance

After multivariable analysis, live birth rate was significantly different depending on blastocyst cryostorage duration (all groups combined) (p = 0.033): live birth rate was significantly lower when blastocyst cryostorage duration was between 12-36 months (OR 0.740 IC95%[0.558; 0.981] p = 0.036) and beyond 36 months (OR 0.674 IC95%[0.456; 0.986] p = 0.044) compared to less than 3 months of blastocyst cryostorage duration. However, no significant impact of blastocyst cryostorage duration was observed on clinical pregnancy rate (p = 0.52).

Limitations, reasons for caution

Our study was limited by its retrospective design with restricted samples.

Wider implications of the findings

This study provides new findings on the effect of blastocyst cryostorage duration with a significant impact on LBR beyond 12 months of vitrification in close system. However, it’s crucial to confirm that cryostorage duration doesn’t lead to adverse obstetric and perinatal outcomes after vitrified blastocyst transfer.

Trial registration number

not applicable
P-305 Detection of GSTM1 polymorphism in women undergoing IVF protocols
Authors: Petsavas A , Stavros S , Mavrogianni D , Drakaki E , Domali E , Drakakis P
Published: June 2023

Study question

Is GSTM1 polymorphism related to infertility and IVF parameters?

Summary answer

Possible correlation between the absence of GSTM1 gene and estradiol levels as well as the fertilized oocytes number, the number of COCs and their quality.

What is known already

Glutathione S-transferase (GST) M1 belongs to a family of detoxification enzymes. GSTM1 detoxifies reactive chemical species, by catalyzing their conjugation to glutathione. Deficiency in enzyme activity is caused by homozygous deletion of the GSTM1 gene. It is known that oxidative stress is a condition that leads to pathophysiological mechanisms related to female infertility Additionally several studies have addressed the possible correlation between female infertility and GSTM1 polymorphisms

Study design, size, duration

One hundred and seventy four samples were collected and divided into 2 groups. The study group was consisted of blood samples from 125 women classified as infertile according to WHO. Blood samples from 49 women classified as fertile with at least one successful pregnancy and nomiscarriages were used for the control group

Participants/materials, setting, methods

For all samples, genetic material(DNA) was extracted. Polymerase chain reaction with specific GSTM1 gene primers followed by agarose electrophoresis was applied to detect the presence of polymorphism.

Main results and the role of chance

Our study showed a significant difference between the presence of GSTM1 gene in the control group when compared with the study group. The results showed for a subgroup of the infertile women,(n = 54), that the estradiol levels were significantly higher, in women who had the GSTM1 gene compared to those who lacked the gene. The fertilized oocytes as well as the number of COCs were significantly higher in women in which the GSTM1 was detected, compared to the women in which the GSTM1 gene was not detected.

Limitations, reasons for caution

Detailed data from all infertile women could further confirm our results.

Wider implications of the findings

The results of the current study may be used for further research related to female infertility and oxidative stress and may clarify the possible interactions between the microenvironment of oocytes and the free radicals. Additionally GSTM1 may be a useful biomarker for predicting IVF results.

Trial registration number

not applicable
P-306 Generalizable AI model for microscopic and timelapse multifocal embryo images
Authors: Lee H J , Kim H M , Choi S , Jung J Y , Park J H , Koo J S K , Min S H , Chung M K , Kim J , Ko T
Published: June 2023

Study question

Can an AI model be applied to datasets with different characteristics?

Summary answer

The AI model predicting pregnancy developed on microscope images can be generally applied to multifocal images from time-lapse system.

What is known already

AI models require large datasets to be able to generalize and handle various scenarios, but it can be challenging to gather enough data for each case. Embryologists evaluate embryos using multiple focal planes and add color filters as needed, and timelapse images have varying features. AI models in past studies were trained using both microscopic and timelapse images, and embryologists question if images must be captured at a specific focal plane for AI to work effectively. In this study, the AI model trained on over 2,000 microscopic embryonic images was validated using timelapse images taken at multiple focal planes.

Study design, size, duration

We collected 2,555 microscopic images from 7 IVF clinics and 1299 timelapse images from 433 embryos from a single IVF clinic between July 2016 and December 2020. The timelapse images were divided into 3 groups, with Group 1 being the best visualized ICM images, Group 2 being 20 µm higher or lower than Group 1, and Group 3 being 20 µm higher or lower than Group 2.

Participants/materials, setting, methods

We built 2 CNN models. The “Microscopic model” and “Timelapse model” were trained and validated using 3-fold cross validation with 2,555 microscopic images, 433 timelapse Group 1 images, respectively. To examine whether the Timelapse model was able to infer well for images taken at different focal points, Group 1, 2, and 3 images were used to test the Microscopic model.

Main results and the role of chance

The AUROCs and accuracies in mean (SD) for the Microscopic model were 0.738 (0.003) and 0.705 (0.011) after 3-fold cross-validation. The AUROC and accuracy for the Timelapse model were 0.627 and 0.583. The AUROCs for Group 1,2, and 3 were 0.699 (0.014), 0.705 (0.001) and 0.701 (0.064), respectively. The accuracies for Group 1,2, and 3 were 0.655. (0.013), 0.647 (0.007), and 0.651 (0.007). The predictive power of the Microscopic model applied to the time-lapse images was better than that of the Timelapse model, although it was not as accurate as the Microscopic model applied to the microscope images.

Limitations, reasons for caution

The limitations of the study include its retrospective nature and a small dataset. Transfer learning of timelapse images to a microscopic model may be beneficial for analyzing timelapse images.

Wider implications of the findings

The study found that timelapse images with multifocal planes can be applied to an AI model built based on a large dataset of microscopic images collected from multiple centers. It may be prudent for a small IVF clinic to apply a generalizable model rather than building its own.

Trial registration number

not applicable
P-341 Endometrial compaction and its impact on reproductive outcome
Authors: Durugkar K , Balkawade N
Published: June 2023

Study question

Is there a relationship between endometrial compaction and clinical pregnancy rate in frozen embryo transfer (FET) cycles?

Summary answer

Clinical pregnancy rate (CPR) were similar in both patients that demonstrated endometrial compaction or no compaction in FETs cycles.

What is known already

There has been increasing interest in the correlation between endometrial compaction and clinical outcomes but there has been conflicting evidence from prior investigations.

Study design, size, duration

Retrospective Observational data Analysis of (n-350) patients undergoing Embryo Transfer during January 2022 to December 2022 at our clinic.

Participants/materials, setting, methods

This study was performed at a single, academically affiliated fertility center in which patients who had an FET using programmed/modified natural cycle protocol were included. Endometrial thickness at time start of progesterone(T1)(TVS) & at time of Embryo transfer (T2)(TAS)was measured, and percentage on ET compaction in both HRT cycle and modified natural cycle was studied. The primary outcome (CPR) was based on proportion of compaction (percentage difference in EMT between T1 and T2).

Main results and the role of chance

Of the 350 participants included, 64%, 38% and10%, of women exhibited >0%, >5% and >10% endometrial compaction, respectively. Endometrial compaction was not predictive of Clinical Pregnancy Rate (CPR) at any of the defined cutoffs .Primary outcomes included CPR (defined as the presence of at least one gestational sac with a fetal pole with cardiac activity on transvaginal ultrasound between 6 and 9 weeks gestation), biochemical pregnancy rate and spontaneous abortion rate. Patients were discharged to their obstetrician when a clinical pregnancy was confirmed between 6 and 9 weeks gestation.

Limitations, reasons for caution

There was the potential for measurement error in the recorded EMTs. The T2 measurement was performed transabdominally, which may cause potential measurement error, as it is generally accepted that transvaginal measurements of EMT are more accurate, though, any bias is expected to be non-differential

Wider implications of the findings

Assessing endometrial compaction may lead to unnecessary cycle cancellation. However, further studies are needed to determine if routine screening for endometrial compaction would improve clinical outcomes.

Trial registration number

not applicable
P-348 Correlation between cesarean scar defect and chronic endometritis and its effect on the pregnancy outcomes of in vitro fertilization
Authors: Xiang R , Li M , Huijun L , Zhi Z , Haitao Z , Jintao P
Published: June 2023

Study question

Do patients with symptomatic cesarean scar defect (CSD) have a higher risk of chronic endometritis (CE) and worse early pregnancy outcomes after hysteroscopic reconstruction for CSD?

Summary answer

Symptomatic CSD has a positive correlation with CE. Antibiotic administration is a promising option for patients with CE to obtain better early pregnancy outcomes.

What is known already

Cesarean scar defect (CSD), a niche-shaped myometrium defect, can be noticed after cesarean sections (CS). Studies about the impact of CSD on fertility are limited. The uterine isthmic region is a sperm reservoir, and CSD may negatively affect natural fertility. CE could reduce endometrial receptivity and thus leads to a lower clinical pregnancy rate. Secondary infertile patients with a history of CS are quite common in the department of reproductive medicine. However, there was still limited data to determine whether CSD correlates with CE, especially in cases suffering from symptomatic CSD with postmenstrual spotting.

Study design, size, duration

This is a retrospective study including 118 patients with a leading symptom of postmenstrual spotting and 224 asymptomatic patients from January 1, 2018 to May 31, 2021.

Participants/materials, setting, methods

Group A was with a leading symptom of postmenstrual spotting, and group B was asymptomatic. Office operative hysteroscopy was performed to correct the CSD for symptomatic patients in group A, and thermoablation of the endometrium in CSD was performed. Out-patient hysteroscopy was performed for asymptomatic patients in group B, and only the morphology of the endometrium was evaluated. Both groups have CD138 immunohistochemistry staining of their endometrium.

Main results and the role of chance

A higher incidence of CE was found in group A compared with group B (50/118 vs. 62/224, P=0.006, OR = 1.921, 95%CI=1.203-3.068). There were no significant differences in the comparisons of chemical pregnancy rate (26/86 vs. 75/216, P=0.455, OR = 0.815, 95%CI=0.475-1.396), ectopic pregnancy rate (1/86 vs. 1/216, P=0.489, OR = 2.529, 95%CI=0.156-40.901), miscarriage rate (6/86 vs. 22/216, P=0.368, OR = 0.661, 95%CI=0.258-1.692), preterm birth rate (2/86 vs. 4/216, P=1.000, OR = 1.262, 95%CI=0.227-7.020) or full-term pregnancy rate (12/86 vs. 35/216, P=0.626, OR = 0.839, 95%CI=0.413-1.704) between the two groups.

Limitations, reasons for caution

First, different doctors might have inconsistent judgments on the definition of postmenstrual spotting. Second, three different operators performed the hysteroscopy. It might contribute to the heterogeneity of the study findings.

Wider implications of the findings

Canalling and thermoablation during hysteroscopy are effective treatments for symptomatic CSD. CSD accompanied by CE should be given more attention before embryo transfer.

Trial registration number

No. 2020A1515110791
P-373 Low-Dose Vaginal Misoprostol Application Before Office Hysteroscopy
Authors: Sarikaya E , Guliyeva M , Kipel R
Published: June 2023

Study question

In gynecological interventional procedures what should be the minimum misoprostol dose for achieving cervical maturation?

Summary answer

50mcgr vaginal misoprostol before office hysteroscopy; decreases the VAS score, bleeding and the total procedure time.

What is known already

Misoprostol has been on the World Health Organization (WHO) essential drugs list since 2005 due to its uterotonic effect.FIGO (The International Federation of Gynecology and Obstetrics) published a posology table in 2017 that does not cause side effects in off-label use of misoprostol in the obstetric field.There are many publications that misoprostol facilitates interventional gynecologic procedures by allowing cervical maturation . However, no guidelines have yet been published on the dose and route of administration

Study design, size, duration

This Prospective Randomized Clinical Research was approved by Ankara City Hospital Clinical Research Ethics and Academic committee . Then, 100 women who underwent office hysteroscopy in Ankara City Hospital Gynecology and Obstetrics Clinic gynecology-infertility outpatient clinic between 01/12/2021-01/05/2022 were included in the study after their informed consent was obtained.

Participants/materials, setting, methods

50 women who self-administered 50 mcg vaginal misoprostol the night before the office hysteroscopy procedure and 50 women who did not administer the drug were compared. The primary outcome of the study was the duration of the procedure, with the pain score during the procedure used being the (VAS) score system. The secondary outcome was procedure and drug-related side effects Statistical evaluation of the data was performed using the SPSS for Windows version 20.0

Main results and the role of chance

In the medicated group the mean of VAS scores during and after the procedure, and the transition and the total time of the procedure were significantly lower than non-medicated group.

Limitations, reasons for caution

In Turkey, there is only one misoprostol product (CYTOTEC Ali Raif İlaç Sanayi A.Ş) with the 200 mcg posology Off label use of misoporostol in obstetrics is legal since 2021 but not for gynecological practice. We do not have country guidelines on misoprostol posology in obstetrics and gynecology usage also

Wider implications of the findings

In gynecological interventional procedures especially before office hysteroscopy, it is important to apply a minimum dose of misoprostol for cervical maturation due to its bleeding-increasing effect in patients whith endometrial polyps or hyperplasia .Because bleeding is the most important factor affecting image quality and procedure efficacy during hysteroscopy.

Trial registration number

E2-21-1068 dated 24.11.2021
P-381 "An Analysis of the Legal Gaps and Jurisprudential Paradigms Surrounding Supernumerary Embryos in Italy: A Comparative Law Approach to Propose Practical Solutions"
Authors: Dalla Costa S
Published: June 2023

Study question

What is the current state of resolving the issue of surplus embryos in Italy, in the absence of clear legislation?

Summary answer

This paper proposes organic reform of Italian law and European harmonization for informed and conscious patient decision-making on excess embryos.

What is known already

According to Italian law, embryos obtained through in-vitro fertilization for assisted reproduction that have not reached the transfer phase (including unsuitable ones) cannot be destroyed, resulting in significant resource allocation for indefinite preservation in biobanks. This stems from the legal and ethical recognition of the human embryo as a subject of rights that in turn prohibits destruction, donation to other couples, or use for scientific research.

Study design, size, duration

My study compares European legal systems and analyzes the evolution of Italian law on medically assisted fertilization (L. 40/2004) since its implementation, with a focus on legal and ethical issues that have been subject of ongoing debate.

It also examines the Italian Ministerial Guidelines, the only text where the legislator has dealt with the issue of surplus embryos.

Participants/materials, setting, methods

Not applicable.

Main results and the role of chance

The present study examines the various approaches taken by countries to address the issue of surplus embryos. Regulations in countries such as Spain, France were taken into consideration. The British legal system is also examined for its regulations on the donation of embryos and reproductive cells. The Spanish regulation of embryo-sharing (L. 14/2006) is the most organic approach. It grants three options to couples with respect to their remaining embryos: preservation for personal use, donation to other couples, or donation for research. In the United States, the increase in cryopreserved and abandoned blastocysts has led to the spread of conditional embryo adoption and Snowflakes adoption. The Italian provision, however, fails to adequately balance the constitutionally protected interests of couples' self-determination and scientific research for the protection of individual and collective health.

Role of chance not applicable here.

Limitations, reasons for caution

Not applicable.

Wider implications of the findings

Italian legislation neglecting to intervene has caused numerous issues, such as increased costs for fertility centers and poor practices. Clinics advertising embryo adoption, despite regulatory uncertainty, have created unfair competition leading to psychological distress for couples with cells in limbo and fears of financial obligations.

Trial registration number

NOT APPLICABLE
P-397 The effect of letrozole overlapped with gonadotropin on IVF outcomes in women with DOR or aged over 40 years old
Authors: Xiaomiao Z , Li X , Li L , He F , Zeng M , Chen X , Ji X , Qiu Q , Yang G , Huang J , Pan P , Guan G
Published: June 2023

Study question

Evaluating the efficacy of modified letrozole protocol (mLP) for diminished ovarian reserve (DOR) or advanced age women.

Summary answer

The modified letrozole protocol provides another option for women with DOR or advanced age, especially those who experienced ovarian stimulation previously.

What is known already

For years, numerous methods have been conducted to obtain better outcomes in women with advanced age or DOR. Increasing doses of gonadotropin (Gn), exogenous luteinizing hormone (LH) or growth factor (GH) supplementation, and various kinds of controlled ovarian stimulation (COS) protocols were reported. However, there is still no consensus due to the contradictory reports of comparable reproductive outcomes. During ovarian stimulation, estrogen and androgen are important in the recruitment of primordial follicles and promotion of follicular growth at the preantral and antral stages across different species.

Study design, size, duration

This is a paired-match study including 243 women with DOR and 249 women aged over 40 years old who received in vitro fertilization (IVF) treatment.

Participants/materials, setting, methods

123 women received stimulation with mLP. GnRH agonist (GnRH-a) long, GnRH antagonist (GnRH-anta), and mild stimulation protocol were used as controls with 123 women in each group. Clinical pregnancy rate (CPR) and cumulative clinical pregnancy rate (CCPR) were main outcomes.

Main results and the role of chance

CPR in the mLP group (38.46%) was significantly higher than mild stimulation (17.11%), but not significantly different from GnRH-a long (26.13%) and GnRH-anta (29.17%) group. CCPR showed an increasing trend in the mLP group (33.33%) although without significance when compared with controls. The CCRP of GnRH-a long, GnRH-anta, mild stimulation group were 21.68%, 29.03%, and 13.01%, respectively. In women with repeated cycles, mLP achieved higher available embryo rate and top-quality embryo rate. Further study showed positive correlation between testosterone and the number of oocytes retrieved in mLP group (r = 0.395, P< 0.01).

Limitations, reasons for caution

It is a retrospective study which resulted in minor bias among mLP and the other control protocols. Although we have already paired for age and AMH, the presence of biases cannot be totally excluded. Further prospective studies need to be done to validate the effect of mLP.

Wider implications of the findings

The modified letrozole protocol may be effective for women with DOR or advanced age, especially those who have experienced previous cycle failure. An increasing serum testosterone level may play a role and reflect follicular growth during ovarian stimulation.

Trial registration number

not applicable
P-508 The adverse effect of a previous late miscarriage on the subsequent pregnancy outcomes: a retrospective cohort study across more than ten years
Authors: Yang L
Published: June 2023

Study question

To explore whether a previous late miscarriage (LM) has a prognostic impact on the subsequent pregnancy outcomes in in-vitro fertilization (IVF) women.

Summary answer

Women who had a LM for unexplained factor or cervical factor following first embryo transfer had a significantly poor pregnancy prognosis after the subsequent transfer.

What is known already

It has been reported that a history of early miscarriages is significantly associated with poor pregnancy outcomes. However, whether and how previous LM might influence future pregnancy outcomes still remain unclear.

Study design, size, duration

A retrospective cohort study was performed among 1072 infertile women who had a LM following the first embryo transfer from January 2008 to December 2020 at Center for Reproductive Medicine, Shandong University.

Participants/materials, setting, methods

1072 infertile women who had a late miscarriage following first embryo transfer were grouped by the causes, 458 women with unexplained factor (unLM), 146 women with fetal factor (feLM), 412 women with cervical factor (ceLM), 56 women with trauma factor (trLM). Subgroup analysis and binary logistic regression were performed to evaluate the associations between late miscarriages with different causes and subsequent pregnancy outcomes.

Main results and the role of chance

Compared with general IVF population, the early miscarriage rate was significantly higher in the unLM group [8.28% vs 13.47%, adjusted OR (95%CI): 1.596(1.119-2.276), P=0.01]. Further, women with a unLM or ceLM had a dramatically elevated risk of recurrent late miscarriage [for unLM:4.24% vs 9.43%, adjusted OR (95%CI): 1.907(1.237-2.939), P=0.003; for ceLM: 4.24% vs 15.53%, adjusted OR (95%CI): 2.682(1.820-3.952), P=0.000] and a consequently reduced frequency of live birth [for unLM: 49.96% vs 43.01%, adjusted OR (95%CI): 0.746(0.612-0.908), P=0.004; for ceLM: 49.96% vs 38.59%, adjusted OR (95%CI): 0.611(0.494-0.756), P=0.000].

Limitations, reasons for caution

This study was limited by the retrospective design from a single center and the sample size in feLM and trLM group is small. Further studies are needed to verify our results and ascertain the mechanisms underlying the reported associations.

Wider implications of the findings

Only one previous late miscarriage resulted from unexplained factor or cervical factor was significantly associated with a higher risk of miscarriage and a lower live birth rate after subsequent embryo transfer. Women with only one late miscarriage should be informed the great risk and given intense surveillance during subsequent pregnancy.

Trial registration number

not applicable
P-519 Is oral dydrogesterone a good alternative to vaginal micronized progesterone for luteal phase support in women receiving oocyte donation?
Authors: Jonard S , Lorillon M , Robin G , Keller L
Published: June 2023

Study question

Does oral dydrogesterone (OD) in luteal phase support (LPS) provide equivalent clinical pregnancy and miscarriage rates as micronized vaginal progesterone (MVP) in oocyte donation recipients?

Summary answer

No significant difference in clinical pregnancy and miscarriage rates was observed when using OD instead of MVP for LPS in oocyte donation.

What is known already

Dydrogesterone has a higher bioavailability than MVP due to its high specificity for progesterone receptors allowing the use of lower doses limiting side effects. In addition, because of its route of administration, its tolerance is better. The use of OD for LPS in fresh IVF cycles is now well recognized. However, few data are available on its use in frozen-thawed embryo transfer especially in artificial cycles. In this situation, the lack of corpus luteum leads to a total dependence on exogenous progestogens for implantation and maintenance of the pregnancy.

Study design, size, duration

A retrospective observational study was performed from prospectively collected data in the ART Department of Lille University Hospital from July 2018 to July 2022.

Participants/materials, setting, methods

Our study analysed 372 oocyte donation cycles with embryo transfer. Recipients underwent endometrial preparation by hormone replacement treatment (artificial cycles). LPS was provided by weekly intramuscular progesterone (500 mg/2ml) and either OD 40 mg per day or MVP 800 mg per day for 12 weeks if the pregnancy test was positive. The primary endpoint was clinical pregnancy rate.

Main results and the role of chance

This study compared the outcome of 162 transfers with dydrogesterone + IM progesterone to the outcome of 210 transfers with the MVP + IM progesterone. No significant difference was found between the two groups except for the number of embryos transferred, embryo quality, donor BMI and fresh or frozen status of the embryo. After adjustment for these criteria, our two groups were comparable in clinical pregnancy rates with 36.67% in the MVP group versus 30.25% in the OD group (OR 0.868 [0.529 ; 1.423], p = 0.57), ongoing pregnancy rates (29.05% versus 25.31%, OR 0.993 [0.591; 1.669], p = 0.97), miscarriage rates (7.62% versus 4.94%, OR 0.640 [0.248; 1.650], p = 0.35) and live birth rates (26.67% versus 17.69%, OR 0.727 [0.412; 1.284], p = 0.27).

Limitations, reasons for caution

The main limitation of this study is the non-randomisation of data between the two treatment groups.

Wider implications of the findings

Our study suggests that dydrogesterone has a place in our LPS strategies in artificial cycle for frozen embryo transfers or in oocyte donation, especially as this route is often preferred by patients and very well tolerated. Further prospective cohorts or randomized trials could continue to inform clinical practice on LPS.

Trial registration number

DEC 16-25
P-520 Risk factors for early pregnancy loss in women undergoing in vitro fertilization-embryo transfer
Authors: He Q , Li X , Ouyang Y
Published: June 2023

Study question

What are the risk factors for early pregnancy loss (EPL) in infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles?

Summary answer

The risk factors for EPL were maternal age, 14-day β-human chorionic gonadotrophin(β-hcg) levels and cycle type.

What is known already

Pregnancy obtained through assisted reproductive technology still has a high risk of spontaneous early pregnancy abortion, and the cause of which is unclear. It not only affects the rate of ongoing pregnancy and live birth, but also increases the psychological and economic burden of patients. At present, there have been many studies on the risk factors of early pregnancy loss in IVF/ICSI-ET at domestic and overseas, but the results are different, which may be related to the selection of different research objects, sample size and statistical methods.

Study design, size, duration

A retrospective study of 6107 embryo transfer cycles collected from January 2018 to December 2018 was performed. The cycles were divided into the EPL group (n = 987) and the live birth group (n = 5120) according to the cycle outcomes.

Participants/materials, setting, methods

Baseline data and clinically relevant indicators were compared between the two groups, including maternal age, infertility years, infertility type, body mass index (BMI), tubal factor, ovulatory dysfunction, endometriosis, male factor, antral follicle count (AFC), single gene related genetic disease, follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), 14-day β-hcg levels, prolactin (PRL), progesterone (P), testosterone (T), anti-Müllerian hormone (AMH), cycle type and the number of transplanted embryos.

Main results and the role of chance

The EPL rate of the infertility patients undergoing fresh/frozen-thaw embryo transfer cycle was 16.16%. Univariate analysis showed that there were statistically significant differences between the two groups in maternal age, AFC, 14-day β-hcg levels, T, AMH, infertility years, cycle type, infertility types, chromosome disease and male factors (P < 0.05). The results of binary logistics regression analysis showed that maternal age, 14-day β-hcg levels and cycle type were related factors to EPL (P < 0.05).

Limitations, reasons for caution

This study lacked some baseline data, such as adverse pregnancy history, abortion history, and previous transplant failure history, and male factors such as BMI, age, semen results, smoking history. The information about fetal chromosomes was also missing.

Wider implications of the findings

Clinical prevention and treatment of risk factors can be targeted to improve pregnancy outcomes after transplantation.

Trial registration number

none