bluuebunny/crossref_metadata_2025_split huggingface dataset:
P–604 Effectiveness comparison of antral follicular count (AFC), follicular-output-rate (FORT), follicle-to-oocyte-index (FOI), oocyte-sensitivity-index (OSI), and follicular-sensitivity-idex (FSI) for predicting clinical pregnancy rates in IVF
Authors: Bayu P , Syam H H 
Published: August 2021

Abstract

Study question
Which is better for predicting clinical pregnancy rate : AFC, FORT, FOI, FSI, or OSI?

Summary answer
Both AFC and OSI can be used to predict clinical pregnancy better than FORT, FOI or FSI.

What is known already
AFC, FORT, FOI, OSI, FSI can be used to predict clinical pregnancy, but no study compared which one is better

Study design, size, duration
Retrospective study using data from medical record (2016–2018) Subjects were patients underwent IVF cycle at Aster Clinic in Hasan Sadikin Hospital Bandung. Subjects divided into 2 groups: clinically pregnant that is visible gestational sac on ultrasound (n = 83) and not pregnant (n = 148). Inclusion criteria : antagonist protocols, &lt;45 years, basal follicle stimulating hormone (FSH) ≤ 12 IU/L, ICSI fertilization method, and fresh transfer cycle.

Participants/materials, setting, methods
AFC categorized &lt; 5 and ≥ 5 (poseidon) FORT=pre-ovulatory follicles(16–20 mm) x 100 divided by AFC(2–10 mm). FOI=oocytes obtained x 100 divided by AFC. OSI=oocytes obtained x 1000 divided by total FSH dose. FSI=pre-ovulatory follicles x 100,000 divided by (AFC x total FSH dose). FORT and FSI divided using percentil 33 and 67. OSI divided into 3 groups by cut-off 1.697/IU for poor-response and 10.07/IU for hyperresponse. FOI divided into 2 groups, ≤ 50% or &gt; 50%

Main results and the role of chance
Group of AFC ≥ 5 had a significantly higher clinical pregnancy rate than the AFC &lt; 5 group (39.49% vs. 16.67% ; p = 0.009). High and moderate OSI had higher clinical pregnancy rate than low OSI (66.37% vs. 37.72% vs. 25.45% ; p = 0.038). There is a significant negative correlation between OSI and age (–0.454) or total FSH dose (–0.594). There is a significant positive correlation between OSI and AFC (0.625), the number of follicles at trigger (0.792), and oocytes (0.923). There were no significant differences in clinical pregnancy rates between the FORT, FOI, and FSI groups.

Limitations, reasons for caution Limitation
Retrospective study using medical record data Ultrasound measurement was done by many reproductive gynecology specialist (not 1 person) --- observer bias.
Wider implications of the findings: This study found no association between FORT, FOI, FSI on clinical pregnancy. Why?
FORT, FSI, FOI use measurement number of follicles at trigger and antral follicle. Differences among observers in interpreting antral follicles and number of follicles at trigger, or inaccurate measurement. No FORT, FOI, and FSI cut off values from previous study.

Trial registration number
Not applicable
P–644 Effect of a reduced dose of long-acting gonadotropin releasing hormone (GnRH) agonist versus short-acting GnRH agonist on pregnancy outcome in patients undergoing ICSI/ET cycles
Authors: Kabodmehri R , Mehrafza M 
Published: August 2021

Abstract

Study question
Are pregnancy outcome different between reduced dose of long-acting GnRH agonist and short-acting GnRH agonist in patients undergoing ICSI/ET cycles?

Summary answer
Clinical outcomes were not significantly different between the two group.

What is known already
There is no consensus on which of two GnRH agonist protocol is the most effective form and it has been challenging which one improves the clinical pregnancy rate.

Study design, size, duration
This is randomized clinical trial that 394 patients, who were candidates for ICSI/ET, were included in this study between April 2019 and January 2020.

Participants/materials, setting, methods
Patients were randomly divided into two groups using blocks of 8; hereby every 8 subjects were randomized, four were allocated to the long-acting GnRH agonist, and four were allocated to the short-acting GnRH agonist randomly.

Main results and the role of chance
No significant difference was noted between the two groups in progesterone and estradiol levels at hCG administration day. Despite no significant difference between the two groups in ART outcomes, interestingly rate of ovarian hyperstimulation syndrome (OHSS) occurrence was significantly higher in the short-acting group (P = 0.005).

Limitations, reasons for caution
We couldn’t evaluate the long-term consequence of pregnancy including live birth rate and effect of GnRH analogue on fetus.
Wider implications of the findings: A lower rate of OHSS occurrence in the long-acting group, and similar ART outcomes in both groups.

Trial registration number
IRCT20190609043845N1
P–649 Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis
Authors: Mizrachi Y , Horowitz E , Gane. Herman H , Farhi J , Raziel A , Weissman A 
Published: August 2021

Abstract

Study question
Should women receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET)?

Summary answer
Progesterone LPS following NC-FET increases the live birth rate. There is no evidence to support the administration of hCG for LPS in these cases.

What is known already
Whether or not women should receive LPS following NC-FET is highly controversial. Previous studies have shown conflicting results.

Study design, size, duration
We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of study-design. The search strategy included keywords related to natural cycle frozen embryo transfer and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded.

Participants/materials, setting, methods
Our systematic search generated 395 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG, and 6 studies (n = 1507) used progesterone for luteal support. Four studies were randomized controlled trials (RCTs), whereas the other four were historic cohort studies.

Main results and the role of chance
In a meta-analysis using random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (two studies, OR 0.85, 95% CI 0.64–1.14). On the other hand, progesterone LPS was associated with a higher clinical pregnancy rate (five studies, OR 1.48, 95% CI 1.14–1.94), and a higher live birth rate (three studies, OR 1.67, 95% CI 1.19–2.36).

Limitations, reasons for caution
There was large heterogeneity in progesterone dose and route of administration, as well as the methods used for ovulation detection and triggering. Moreover, only four studies were randomized. Finally, both studies examining the use of hCG for LPS were performed by the same group of researchers in a single center.
Wider implications of the findings: The available evidence indicates that progesterone administration for LPS is beneficial following natural cycle frozen embryo transfer. There is no evidence to support the administration of hCG for LPS in these cases. Additional Large RCTs are necessary in order to improve the quality of evidence and validate our findings.

Trial registration number
PROSPERO ID: CRD42020199045
P–664 Bone morphogenetic protein–7 (BMP–7) reduces E2 and P4 production of human luteinized granulosa cells by down-regulating the expression of the steroidogenic enzymes StAR and 3B-HSD
Authors: Yildiz C S , Oktem O 
Published: August 2021

Abstract

Study question
What is the biological role of BMP–7 on the granulosa cells after luteinization?

Summary answer
BMP–7 down regulates the steroidogenic enzymes and reduces E2 and P4 output of luteinized granulosa cells.

What is known already
BMP–7 is a member of TGF-B super family that is mainly produced by theca cells in the ovary. It promotes the transition of primordials into primary follicles, and the growth and preantral and antral follicles, and inhibits progesterone (P4) production during FSH-induced growth phase of Graafian follicles (luteinization inhibitor). However, limited data is available regarding the role of this hormone on the molecular luteal characteristics of granulosa cells after ovulation and luteinization processes. We therefore aimed to address this issue in the current study.

Study design, size, duration
A basic science study on the corpus luteum biology

Participants/materials, setting, methods
Human luteal granulosa cells were obtained from 10 normo-responder IVF patients undergoing ovarian stimulation with rec-FSH and GnRH antagonist protocol and cultured with recombinant forms of BMP–7, hCG and activin-A for 24h. The presence of cognate receptors for these hormones were validated using RT-PCR. The expression of the steroidogenic enzymes were analyzed with quantitative immunoblotting, real-time RT-PCR and confocal microscopy. E2 and P4 production of the cells were measured using ECLIA method.

Main results and the role of chance
BMP–7 significantly down-regulated the expression of StAR and 3b-HSD in immunoblotting and confocal images and caused a substantial decrease in P4 production in the luteal GCs in a dose dependent manner. It did not cause any notable change in aromatase expression, however E2 output declined in parallel with P4 due to the reduced expression of StAR, which is the rate limiting enzyme in steroidogenesis. hCG significantly up-regulated StAR and 3b-HSD expression and enhanced P4 output whereas activin-A did the opposite effect. Viability assay with Yo-PRO–1 uptake assay did not reveal any significant differences in the viability of the cells before and after treatment with these hormones.

Limitations, reasons for caution
In-vitro findings requires validation using in-vivo models.
Wider implications of the findings: Reversal of luteinization and down-regulation of steroidogenesis with BMP–7 and other hormones with similar actions warrant further investigation to test their in-vivo effects in order to develop new strategies against ovarian hyperstimulation syndrome (OHSS).

Trial registration number
Not applicable
P–670 Urine estrone–3-glucuronide (E3G) assay: is there any place during ovarian stimulation for IVF cycles?
Authors: Vladimirov I , Martin V , Desislava T 
Published: August 2021

Abstract

Study question
Could the urine estrone–3-glucuronide (E3G) assay be used efficiently to monitor a controlled ovarian hyperstimulation (COH) cycle, in comparison to a serum estradiol (E2) assay?

Summary answer
E3G testing provides an alternative to serum E2 assessment and a new “patient friendly” approach for COH monitoring.

What is known already
In many IVF clinics basic monitoring tools for controlled ovarian stimulation during IVF procedure are ultrasound measurements of follicle growth and hormone assessment of serum E2 levels. The monitoring can occur 4–6 times during stimulation, but repeated blood sampling causes patient stress. In contrast, E3G sampling, one of principal metabolites of estradiol in urine, is non-invasive and can be performed by the patients themselves and measured by fluorescent immunoassay. A correlation has been shown between concentrations of E2 present in plasma and concentrations of E3G in different phases of menstruation cycle.

Study design, size, duration
This is a pilot, prospective study, in a single IVF clinic. Twenty female participants were recruited November 2020 -January 2021, aged 25–43 years and BMI: 18–28kg/m2. Dynamic change of serum E2 and urine E3G at ovarian stimulation monitoring are being analyzed.

Participants/materials, setting, methods
Concurrent urine E3G and serum E2 values were collected from patients who provided between 2 and 4 samples on different days of their COH IVF cycle. Serum E2 values were assessed routinely, while E3G values were measured and validated using a fluorescent immunoassay Mira Fertility Plus® analyzer.Main results and the role of chance: The urine E3G of assay was validated for intra- and inter-assay variability with a coefficient of variation of &lt; 20%. It was also validated for analytical and functional sensitivity and sample stability. Linear regression of serum E2 and E3G values of 56 early morning urine samples who had evaluated between Days 4 and 13 of menstruation cycle provided an R = 0,81. Urine E3G values also correlated to follicle growth. Patient survey results showed that urine sampling was the preferred method of analysis.

Limitations, reasons for caution
We have provided proof of principle that urine E3G measurement can be accurately carried out using fluorescent immunoassay technology during routine COH for IVF cycles. The patients’ study group has to be expanded in order to enable us to find the appropriate place of urine E3G assay in COH protocol.
Wider implications of the findings: Urine E3G testing correlates well to serum E2 assessment in COH. Urine E3G assay provides an alternative to serum-based assessment. The ease of urine sampling allows a reduction in patient discomfort during venopuncture, costs, time, and infection risks in epidemics/pandemics, like COViD–19, and offers a patient-friendly approach to ovarian stimulation.

Trial registration number
NA
P–673 A visualized clinical model predicting cumulative pregnancy rate after IVF-ET: a real-world study
Authors: Zhang M 
Published: August 2021

Abstract

Study question
How is the cumulative pregnancy probability of individual patients after IVF-ET,could we develop a visualized clinical model to predict it based on patient’s characteristics?

Summary answer
The visualized clinical mode incorporates five items of female age, number of oocytes, antral follicle count, endometrium thickness and basal FSH level.

What is known already
Many factors can result in infertility, prognosis prediction is clinically relevant for making the right therapeutic strategy while avoiding overtreatment. It is also helpful in counselling, making the patient aware of possible treatment duration and estimated expense and managing patient’s expectation. Visualized clinical mode and accurate prediction would also be helpful in designing clinical trials to evaluate new treatments.

Study design, size, duration
We conducted a retrospective analysis of a single-center database using prospectively collected data from women who underwent IVF/ICSI treatment from January 2013 to December 2015, All the participants were followed up for at least 2 years, 3538 IVF-ET cycles were included in the study.A total of 3538 IVF/ICSI cycles were included in the study.

Participants/materials, setting, methods
Data from a total of 2312 IVF/ICSI cycles from January 2013 to December 2014 were randomly split into training dataset (1550, 67%) and internal validation dataset (762, 33%). A total of 1226 IVF/ICSI cycles in 2015 was applied to external validation dataset (temporal validation)

Main results and the role of chance
Multivariable logistic regression model combined with restricted cubic splines function was used to test independent prognostic factors and estimate their effects on treatment outcome for patients treated with IVF/ICSI. Female age, number of oocytes retrieved, AFC, endometrium thickness and basal FSH were included the final model. The above model was used to calculate prediction scores for all women in the training and validation datasets. The C-index was 0.693 (95% CI: 0.692∼0.695) in training sets, 0.689 in internal validation sets and 0.710 in external validation sets, which denotes a good performance. Calibration curves suggest excellent model calibration, with an ideal agreement between the prediction and actual observation . The DCA showed that if the threshold probability is between 0 and 0.7, using the nomogram derived in the present study to predict cumulative pregnancy provided a greater benefit than either thetreat-all or the treat-none strategy.

Limitations, reasons for caution
it was a retrospective, single-center study.In the future, prospective, randomized controlled, multicenter clinical studies will be designed.
Wider implications of the findings: The visualized nomogram model provides great predictive value for infertility patients in their first IVF/ICSI cycle, and predicts the pregnancy probability of individuals ,and could help clinicians improving clinical counselling.

Trial registration number
Not applicable
P–700 Increased progesterone to mature oocyte index is associated with lower top-quality embryo rate in GnRH antagonist protocols
Authors: Şükür Y E , Pouya K , Özmen B , Sönmezer M , Berker B , Atabekoğlu C S , Aytaç R 
Published: August 2021

Abstract

Study question
Do progesterone elevation (PE) on trigger day and progesterone to mature oocyte index (PMOI) affect embryo quality and the chance of live birth?

Summary answer
The top-quality embryo rate is decreased by increasing PMOI, but it has no association with absolute serum progesterone levels.

What is known already
Progesterone elevation have been reported to significantly decrease pregnancy and implantation rates. The main mechanism of this adverse effect is mainly related to an asynchrony between the endometrium and the embryo. Many of the previous studies have failed to show a significant impact of PE on embryo quality and the success of subsequent frozen-thawed embryo transfer (FET) cycle. However, PMOI was suggested to be more predictive than PE of ART outcome and might be associated with embryo quality.

Study design, size, duration
A single-centre retrospective cohort study was conducted. All FET cycles performed in a university hospital infertility centre between January 2016 and December 2019 were reviewed. A total of 44 patients who had PE (&gt;1.5 ng/ml) on trigger day and 134 patients who did not have PE were assessed.

Participants/materials, setting, methods
The study group consisted of patients who had PE (&gt;1.5 ng/mL) during fresh COS cycle and the control group consisted of patients who did not have PE. In addition to effect of PE on subsequent FET cycle outcome, an association between PMOI and embryo quality was assessed. The threshold level to define increased PMOI (&gt;0.12 ng/ml) was calculated as the median level of the whole study cohort.

Main results and the role of chance
The mean ages of the study and control groups were 30.4±5.4 years and 31.1±5.6 years, respectively (P = 0.413). Although the number of oocytes collected and MII oocytes were significantly higher in patients with PE, the total number of frozen embryos were similar between the groups. There were no significant differences concerning the outcome measures including live birth rate in the subsequent FET cycle between participants with and without PE (27.3% vs. 23.9%, respectively; P = 0.652). The rate of top-quality embryos was similar between participants with and without PE (43% vs. 52%, respectively; P = 0.370). However, the rate of top-quality embryos was significantly lower in cycles with PMOI&gt;0.12 ng/ml than in cycles PMOI&lt;0.12 ng/ml (42% vs. 56%, respectively; P = 0.027).

Limitations, reasons for caution
The retrospective design and the small sample size derived from a single institution.
Wider implications of the findings: Increased PMOI, which is associated to lower top-quality embryo rate, may in turn result in diminished cumulative live birth rate.

Trial registration number
Not applicable
P–709 Dual stimulation in-vitro-maturation (Duostim IVM) for overcoming oocyte maturation arrest, resulting in embryo transfer and livebirth
Authors: Hatirnaz S , Hatirnaz E , Dahan M , Ata B , Basbug A , Hatirnaz K , Tan S 
Published: August 2021

Abstract

Study question
Does luteal phase followed by follicular phase letrozole priming and dual oocyte retrieval for in-vitro maturation (IVM) overcome oocyte maturation arrest (OMA)?

Summary answer
Oocyte maturation, fertilization,embryo cryopreservation and livebirth can be achieved with letrozole priming IVM in rare cases of OMA.

What is known already
OMA is an intractable problem resulting in only immature oocytes being collected and to date no succesful treatment exists. Attempts to mature oocytes collected in stimulated IVF cycles with OMA have so far failed. Cases with OMA can be due to intrinsic oocyte defects, intrafollicular factors or resistance to stimulation.

Study design, size, duration
Six women with OMA in ≥ 2 prior stimulated IVF cycles were treated between March 2019 and December 2020.

Participants/materials, setting, methods
Participants had total of 18 (range 2 - 6) prior IVF cycles yielding only 166 immature oocytes. Letrozole 5mg was given days 15–18 of ovulatory cycle; SC decapeptyl 0.1mg trigger given at follicles 12 mm, 38 hours&lt;OPU. After menstruation, letrozole 5mg days 3–7; SChCG 250ug when follicles=12 mm 38 hours&lt;OPU. After in-vitro-maturation oocytes reaching MII were fertilized. Embryos from luteal collection were frozen and fresh embryo transfer was attempted after follicular phase collection.

Main results and the role of chance
Six women underwent DuoStim IVM, median (quartiles) 3.5 (0 - 9) GV and 0.5 (0 - 2) MI oocytes were collected from luteal phase OC and 0 (0 - 0) GV and 2(0 – 4.5) MI oocytes were collected from follicular phase OC. They had a total of 166 immature oocytes collected in prior IVF cycles. There were no MII oocytes at the time of collection in any cycles.0 (0 – 3.5) oocytes matured from luteal phase OC and 1 (0 – 4) from follicular phase OC. 0 (0 – 1.5) embryos were available from luteal phase and 0 (0 - 2) from follicular phase OC.Two subjects (29 and 33 years old) underwent fresh DET and the 29 year old with 2 previous failed IVF cycles achieved a livebirth (50% per ET and 16.7% per started cycle). None of the women who did not have an embryo for fresh transfer from the follicular phase collection had an embryo from the luteal phase collection. The same 29 year old has 2 luteal phase and 2 more follicular phase embryos vitrified.

Limitations, reasons for caution
OMA is a rare condition with a variety of etiologies. Different etiologies can require different managements.
Wider implications of the findings: It may be possible to overcome OMA with letrozole IVM in rare cases. This case is the first recorded live birth. The value of dual stimulation overcoming OMA remains uncertain.

Trial registration number
This study is approved by the local ethical commitee of Medicana Samsun International Hospital by a Grant number of 02/05.02.2020: registration is not required due to retrospective status