bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-207 Molecular mechanisms of melatonin action in human reproductive system – implications for assisted reproduction
Authors: Nikolov G , Konakchieva R , Nikolaev G , Marinova E 
Published: June 2022

Abstract

Study question
What is the potential role of melatonin and melatonin receptors activation on the reproductive function in humans?

Summary answer
The presence of membrane melatonin receptors in male gametes and female hGLCs suggests a role for melatonin on motility performance of mature spermatozoa and oogenesis.

What is known already
The interest in the influence of the external environment on the reproductive performance in humans facilitates reevaluation of its main mediators in the body. One of the most important among them is melatonin circadian secretion by the pineal gland, a major synchronizer of the diurnal rest-activity cycle. Activation of melatonin-linked GPCR receptors by melatonin is coupled to inhibition of cAMP accumulation in target cells, which makes research on membrane receptor-mediated signaling in human reproductive system very attractive.

Study design, size, duration
Pilot study on the presence of MT1 and MT2 receptors in human spermatozoa and human granulosa luteinized cells (hGLCs) and the presence and localization of α- and ß-tubulin, melatonin receptors (MT1, MT2) and P450 aromatase in hGLCs.

Participants/materials, setting, methods
Human donor samples (spermatozoa and granulosa lutein cells (hGLC) were collected after informed consent signed from patients recruited at IVF clinics in Sofia. Two-step quantitative real time RT-PCR (qRT-PCR) was used to compare individual variations between donors. Selected proteins in samples and derived cell cultures like α- and ß-tubulin, melatonin receptors (MT1, MT2) and P450 aromatase were studied by Western blotting and localization visualized by confocal immune fluorescence.

Main results and the role of chance
PCR amplification of cDNA in the samples resulted in products of the expected size of 516 bp corresponding to the MTNR1A gene. In purified spermatozoa, intense expression of a MT1 receptor was found in the post-acrosomal region and the neck. In hGLC cultures up-regulation of melatonin receptors after in-vitro melatonin treatment was observed both by protein expression and densitometry of immune fuorescence.
Our results demonstrate the presence in situ of membrane melatonin receptor in competent human male gametes and female hGLCs. The observed localization of the receptor protein suggests a role for melatonin on motility performance of mature spermatozoa, which may have several important implications to assisted reproductive techniques.

Limitations, reasons for caution
The discrete functional responses and the transduction pathways linked to specific receptor activation by melatonin in human reproductive system have further to be elucidated.

Wider implications of the findings
Future studies could reveal the potential therapeutic role of Melatonin in infertility patients.

Trial registration number
Not applicable
P-223 Women aged 40 or older and non-male factor have the same reproductive outcome using intracytoplasmic sperm injection (ICSI) or conventional in vitro fertilization (cIVF)
Authors: Filardi P , De Martino E , Chiarello Sosa J.M , Gomez Peña M , Papayannis M , Figueroa C , Magri L , Oubiña A , Horton M , De Zuñiga I , Kopcow L , Sobral F , Bisioli C 
Published: June 2022

Abstract

Study question
Do women aged 40 or older have the same reproductive outcome using ICSI or cIVF when male factor infertility is not present?

Summary answer
Women aged 40 or older with non-male factor partners achieved similar reproductive outcomes either with ICSI or cIVF.

What is known already
Although initially proposed to treat couples with severe male factor infertility, ICSI has become the preferred tool to treat patient populations others than initially intended. Many studies and international forums, however, have alerted that its overuse is not free due to its safety, cost and time-consuming concerns. Moreover, it was noted that it does not increase clinical outcomes even in cases of compromised oocyte factor such as poor responder patients or few oocytes retrieved. However, there is still no information regarding its use in the group of patients of advanced reproductive age.

Study design, size, duration
Retrospective cohort study including 412 women aged 40 or older with non-male factor infertility performing ICSI or cIVF between May 2015 and October 2017.

Participants/materials, setting, methods
Patients underwent ICSI (n = 109) or cIVF (n = 303) according to medical indication. The decision to use ICSI in non-male factor patients was merely operational, with the objective of evaluating oocyte maturity.Those cycles with own oocytes, non-male factor and fresh embryo transfers were included. Semen samples were considered normal following the World Health Organization fifth edition sperm parameters values, and prepared by density gradient selection.

Main results and the role of chance
The primary outcome was clinical pregnancy rate. Secondary outcomes included ongoing pregnancy, miscarriage and implantation rates. Statistical significance was denoted by P &lt; 0.05. The mean age of the women were 41.4 in the ICSI group and 41.6 years in the cIVF group, while the mean age for male couple was 43.6 and 41.6 respectively.
No differences between ICSI and cIVF groups were observed regarding clinical pregnancy [16.5% (18/109) vs. 20.8% (63/303)], ongoing pregnancy [9.2% (10/109) vs. 7.9% (24/303)], miscarriage [41.2% (7/17) vs. 46,5% (20/43)], and implantation rates [11.3% (17/151) vs. 9.9% (50/506)].

Limitations, reasons for caution
These results need confirmation with a bigger population size. As with any retrospective study, the potential for residual confounding exists.

Wider implications of the findings
These data suggest that ICSI offers no clinical benefit for women aged 40 and older with non-male factor infertility, beyond oocyte maturation classification.

Trial registration number
not applicable
P-284 Correlation between a new day 4 embryo scoring system and blastocyst development and pregnancy rate
Authors: Martello C , Andrade G , Frantz G , Pagnoncelli N , Dutra C , Rockenbach M , Donatti L , Frantz N 
Published: June 2022

Abstract

Study question
Does a new day 4 embryo scoring system predict blastocyst development and aneuploidies?

Summary answer
The new day 4 embryo scoring system correlates with blastocyst development, blastocyst morphology, day of blastulation, and pregnancy rate.

What is known already
A small number of studies propose different day 4 embryo grading systems. The majority of them report no differences in implantation and clinical pregnancy outcome between day 4 and blastocyst transfer. Moreover, only limited data exist on the association between day 4 grading systems, embryo development, and PGT-A results. In addition, none of the previous studies analyzed the totality of the different day 4 embryo morphology and their subsequent development.

Study design, size, duration
This is a single-center retrospective analysis from June 2019 to August 2021 including 762 embryos from 129 cycles. Day 4 embryos were graded A to J considering A the best morphology and were classified into 1, 2, 3, or 4 categories (1 being the more advanced development). Categories were compared among them to assess blastocyst development and aneuploidy rate.

Participants/materials, setting, methods
Data were obtained from medical records with a previously given consent. Patient characteristics such as age, body mass index (BMI), and anti-Mullerian hormone (AMH) were compared among the four categories using ANOVA with Multiple Comparisons. Blastocyst development, blastocyst morphology, day of blastulation, and pregnancy rate were compared among the categories using Chi-square contingency. All analyses considered a significant p-value of 0.05.

Main results and the role of chance
Younger women presented significantly more category 1 of day 4 embryos when compared with the other categories (p &lt; 0.0001). BMI and AMH were similar among the categories (p = 0.3063 and p = 0.2533, respectively). There was a high correlation between day 4 categories and PGT-A blastocyst development (p &lt; 0.0001), blastocyst morphology (p &lt; 0.0001), and day of blastulation (p &lt; 0.0001). Also, there was a significant correlation between pregnancy rates and the four categories (p = 0.0192). No correlation was observed when aneuploidy rate and level of aneuploidy were analyzed (p = 0.3614 and p = 0.1490, respectively).

Limitations, reasons for caution
The limited number of embryos analyzed is a limitation of the study, and additional data are being gathered. Multiple embryos of the same patients can be a cofounder of the study and more robust statistical analysis may overcome it.

Wider implications of the findings
The new day 4 embryo score may be useful for embryo selection to PGT-A biopsy. Moreover, the proposed score may help to add valuable information to select the best embryos for transfer.

Trial registration number
not applicable
P-353 Placenta previa in In Vitro Fertilization and unassisted pregnancies – is there a difference in perinatal outcomes and placental histology?
Authors: Barber E , Ganer Herman H , Kovo M , Tairy D , Schreiber L , Horowitz E , Weissman A , Weiner E , Raziel A 
Published: June 2022

Abstract

Study question
Why is In-vitro-fertilization (IVF) an independent risk factor for placenta previa (PP).

Summary answer
While PP in non-assisted pregnancies is probably associated with previous cesarean deliveries (CD), in IVF it is more “sporadic”, and may complicate any index pregnancy.

What is known already
PP is more prevalent following IVF pregnancies as compared with unassisted pregnancies, with an increased risk of three to six-fold according to some authors. The etiology for this increased risk in IVF pregnancies in unclear, and may be related to reproductive procedures performed or to subfertility characteristics which have led to IVF.

Study design, size, duration
A retrospective-cohort study of deliveries with PP between 2008 and 2021. A total of 182 pregnancies were included.

Participants/materials, setting, methods
Placental histopathology, obstetric and neonatal outcomes were compared between IVF and unassisted pregnancies. Included, were singleton deliveries complicated by PP at gestational weeks (GA)&gt; 24. Placental pathology was obtained utilizing the well-accepted Amsterdam criteria.

Main results and the role of chance
Out of 182 pregnancies which were included - 23 IVF pregnancies (IVF group) and 159 in the unassisted pregnancies (Control group). The control group was characterized by higher gravidity (p = 0.007) and parity (p &lt; 0.001), whereas the IVF group- by a higher rate of nulliparity (p &lt; 0.001) and diabetes mellitus (p = 0.04). A higher rate of patients with past CDs was noted in unassisted pregnancies, although not statistically significance (38.9% versus 21.7%, p = 0.10). There was a trend for a lower placental weight in the control group, and a higher incidence of placental weight below the 10thpercentile in this group (47.8% versus 13.9%, p = 0.001). No differences were noted in maternal and fetal vascular lesions. Nevertheless, IVF and unassisted pregnancies entail similar perinatal outcomes in cases of PP.

Limitations, reasons for caution
A major limitation was our small sample size in the IVF group. Despite a power calculation, larger study groups would have possibly allowed for the demonstration of additional differences in outcomes, including previous cesarean deliveries and placenta accreta. Moreover, this limitation prevented us from matching against possible cofounders.

Wider implications of the findings
While a growing proportion of pregnancies worldwide are conceived by IVF, possible iatrogenic side effects should be studied. As PP is of clinical importance, it is essential to diagnose it on time, as well as study the mechanisms and risk factors behind it, which could possibly help with its prevention.

Trial registration number
0282-20-WOMC
P-368 Serum progesterone on the day of embryo transfer in stimulated cycles does not correlate with pregnancy outcomes
Authors: Rozen G , Rogers P , Polyakov A 
Published: June 2022

Abstract

Study question
Is the chance of positive hCG, clinical pregnancy or live birth in a fresh embryo transfer (ET) IVF cycle, affected by day of transfer serum progesterone (P4) level?

Summary answer
There is no correlation between P4 level on the day of ET and pregnancy outcomes.

What is known already
Data from studies of frozen–thawed embryo transfer cycles suggest that low as well as high P4 levels during the mid-luteal phase may decrease the chance of pregnancy. The altered P4 pattern may disrupt the endometrial maturation leading to asynchrony between embryonic development and endometrial receptivity, thereby, compromising implantation and early development of pregnancy.

Study design, size, duration
A monocentric retrospective study of prospectively collected data, of women undergoing IVF or ICSI treatment July 2019-July 2020, and having a fresh day 5 single embryo transfer (SET). 825 first and second stimulation cycles were included. Patients underwent a GnRH-antagonist protocol and were triggered for final oocyte maturation with hCG (OvidrelR). All patients received vaginal luteal support. The study population was unselected, treated with the unit’s usual stimulation protocols, representing an everyday patient cohort.

Participants/materials, setting, methods
Serum P4 levels on the day of ET were correlated with positive hCG, clinical pregnancy (CP) and live birth (LB) rates. Based on previously defined P4 thresholds, patients were divided into four P4 groups based on serum levels (P4&lt;150 nmol/l, P4 150–250 nmol/l, P4 251–400 nmol/l and P4&gt;400 nmol/l). The data was further interrogated using additional P4 cut offs, to confirm that there were no discernible differences based on P4 levels.

Main results and the role of chance
There was no level of P4 below or above which the chance of pregnancy was consistently reduced. The chance of a positive hCG-test in the whole cohort was 51%, (95% CI: 47.1-54) following blastocyst transfer and was not different across the four groups (50, 48.2, 51.1, 52%, P = 0.88). Likewise, there was no difference in CP 41.8% (CI 38.4-45.3%) and LB 30.4% (27.3-33.7%), between the four groups. No negative association between P4 and chance of pregnancy when the other thresholds, described above, were applied. All estimates were adjusted for maternal age, maternal BMI, eggs retrieved and number of eggs fertilised, with the outcome remaining unchanged.

Limitations, reasons for caution
The finding of no difference in pregnancy outcomes across P4 ranges in this study, only applies to fresh blastocyst transfer IVF cycles, using hCG trigger and vaginal LPS, and should be corroborated in future clinical trials. Also, there is possible inaccuracy in P4 levels due to diurnal variability.

Wider implications of the findings
Future studies are necessary to explore the diurnal variability, and its possible contribution to these results.

Trial registration number
retrospective study, institutional ethics approval
P-445 Recovery of metabolic activity and VEGF secretion after thawing of cryopreserved, slow frozen ovarian tissue
Authors: Einenkel R , Schallmoser A , Saenger N 
Published: June 2022

Abstract

Study question
Is slow-frozen ovarian cortical tissue limited in its metabolical activity after thawing, especially with respect to VEGF secretion?

Summary answer
Slow-frozen ovarian cortical tissue showed decreased metabolic activity and VEGF directly after thawing, but recovered in the course of 48h in in vitro culture.

What is known already
Cryopreservation of ovarian cortical tissue has become an important method in fertility preservation. Freezing and thawing processes had been optimized to preserve tissue viability. However, the major obstacle of retransplantation is the rapid angiogenesis to accomplish sufficient blood supply. As freezing and thawing entails constraints in cellular metabolic activity, we aimed to assess the metabolic activity and the secretion of the angiogenic factor VEGF of frozen-thawed ovarian cortical tissue over time.

Study design, size, duration
Ex vivo gained ovarian tissue was cultured over 48h. Thereby, non-frozen fresh tissue was compared to slow-frozen-thawed ovarian tissue.

Participants/materials, setting, methods
Provided a signed consent, biopsies of ovarian tissue from patients undergoing fertility preservation were cultured without freezing (n = 13) or after slow-freezing and thawing (n = 12). VEGF secretion during 48h was measured by ELISA. Applying CellTiterBlue assay, metabolic activity was assessed in biopsies without freezing or after thawing from the same patients (n = 4-7) after 0, 24 and 48h. Similarly, VEGF secretion was measured after 0, 24 and 48h as well (n = 7) to capture temporarily changes.

Main results and the role of chance
Although VEGF secretion varies among patients and biopsies, there was a significant lower VEGF content in supernatant from frozen-thawed tissue compared to fresh ovarian cortical tissue after 48h of culture (p &lt; 0.01). Directly after thawing and 24h thereafter, metabolic activity was significantly reduced (p &lt; 0.05) compared to fresh ovarian cortex. In the course of 48h, the metabolic activity recovered (p &lt; 0.01). Similarly, VEGF secretion increased dramatically during 24h after thawing (p &lt; 0.05).

Limitations, reasons for caution
This in vitro study might not resemble the metabolic and secretory recovery after retransplantation.

Wider implications of the findings
We showed that ovarian tissue recovers metabolically over 48h. This recovery included an increase in VEGF secretion. As latter induces angiogenesis a culture step after thawing might support VEGF secretion and angiogenesis. However, the recovery period could also be useful as a temporal bridge until sufficient supplies are available.

Trial registration number
not applicable
P-659 Does Preconception thyroid-stimulating hormone (TSH) levels affect the clinical outcomes of Infertile Women Undergoing Fresh Embryo Transfer Cycle?
Authors: Song G.Y , Park E.A , Lee J.H , Ryu H.E , Park S.J , Hur Y.J , Yu E.J , Lee K.A , Yoon T.K 
Published: June 2022

Abstract

Study question
Does Preconception TSH levels affect the clinical outcomes of Infertile Women Undergoing Fresh Embryo Transfer Cycle?

Summary answer
Among euthyroid patients, preconceptional TSH values in the high-normal range (between 2.5 and 4.0 mIU/L) are associated with adverse clinical outcomes.

What is known already
Serum thyroid-stimulating hormone (TSH) levels are routinely screened in women with infertility given the negative impact of thyroid disease on ovarian function and pregnancy is associated with poor outcomes.In fact, an underlying thyroid abnormality was found in 46% for women experiencing IVF failure and TSH levels were inversely proportional to the fertilization rate at IVF. While it is clear that pregnancies complicated by subclinical hypothyroidism in the fertile population have poor outcomes, the relevance of preconception subclinical hypothyroidism in infertile patients undergoing ART has not been thoroughly examined.

Study design, size, duration
Outcomes of all fresh IVF patients with an embryo transfer from from January 2019 to August 2021 within 1 yr of TSH screening at a our center were studied. IVF cycles using donor oocyte, TESE sperm, PGT, or those lacking follow-up were excluded. For patients with more than one Preconception TSH measurement prior IVF, the most recent measurement before the IVF cycle was used.

Participants/materials, setting, methods
Cycles were categorized into two groups based on preconceptional TSH values: Euthyroid (0.4–2.5 μIU/mL), subclinical hypothyroidism (&gt;2.5-4.0 μIU/mL). All women underwent standard IVF protocols following usual individualized practice in our IVF clinic. Chi-square test was used to evaluate the differences between the patient cohorts.

Main results and the role of chance
A total of 2,669 fresh-ET cycles were reviewed retrospectively by dividing them into a euthyroid group (0.4-2.5 uIU/mL, n = 2397) and subclinical hypothyroidism group (2.5-4.0 uIU/mL, n=272). The overall biochemical pregnancy rate and clinical pregnancy rate was significantly lower in women with subclinical hypothyroidism (50.0% vs 43.4%, 40.0% vs 30.9%, p &lt; 0.05). However, biochemical preganacy loss rate and the miscarriage rate was higher in women with subclinical hypothyroidism. (19.6% vs. 28.8%, 17.3% vs. 25.0%, p = 0.079)

Limitations, reasons for caution
This is a retrospective study and results must be confirmed on a well-designed randomized controlled study. Correlations must be considered with caution since the role of TSH is under study, especially when considering LBR outcome.

Wider implications of the findings
Among euthyroid patients, preconceptional TSH values in the high-normal range (between 2.5 and 4.0 mIU/L) are associated with adverse clinical outcomes. Our findings suggest that subclinical hypothyroidism may affect clinical outcomes.

Trial registration number
not applicable