Pigment epithelium-derived factor expression and role in follicular development.

RESEARCH QUESTION: What is the involvement of pigment epithelium-derived factor (PEDF), expressed in granulosa cells, in folliculogenesis? DESIGN: mRNA expression of PEDF and other key factors [Cyp19, anti-Müllerian hormone receptor (AMHR) and vascular endothelial growth factor (VEGF)] in mice follicles was examined in order to typify the expression of PEDF in growing follicles and in human primary granulosa cells (hpGC), and to follow the interplay between PEDF and the other main players in folliculogenesis: FSH and AMH. RESULTS: mRNA expression of PEDF increased through folliculogenesis, although the pattern differed from that of the other examined genes, affecting the follicular angiogenic and oxidative balance. In hpGC, prolonged exposure to FSH stimulated the up-regulation of PEDF mRNA. Furthermore, a negative correlation between AMH and PEDF was observed: AMH stimulation reduced the expression of PEDF mRNA and PEDF stimulation reduced the expression of AMHR mRNA. CONCLUSIONS: Folliculogenesis, an intricate process that requires close dialogue between the oocyte and its supporting granulosa cells, is mediated by various endocrine and paracrine factors. The current findings suggest that PEDF, expressed in granulosa cells, is a pro-folliculogenesis player that interacts with FSH and AMH in the process of follicular growth. However, the mechanism of this process is yet to be determined.

PGT pregnancies have a similar risk for post-partum complications as naturally conceived pregnancies.

RESEARCH QUESTION: Do preimplantation genetic testing (PGT) pregnancies have higher post-partum complications compared with naturally conceived pregnancies? DESIGN: Retrospective cohort study conducted in 2008-2020 at the Shaare Zedek Medical Center (SZMC), including all patients aged 18-45 years old who conceived following PGT with a singleton live birth >24 weeks. Data were collected from computerized hospital databases and patient files. There were two control groups: (i) pregnancies following IVF-ICSI (intracytoplasmic sperm injection); (ii) four neighbourhood controls for each case delivery (two women delivered before and two after) of women with naturally conceived pregnancies. RESULTS: Overall, 120 PGT, 779 IVF-ICSI and 3507 naturally conceived deliveries were included. Demographic variables were similar apart from slightly higher age in the PGT (P = 0.003) and ICSI (P = 0.002) groups (31.07 ± 4.38 PGT, 31.66 ± 5.03 ICSI, 28.77 ± 5.72 naturally conceived). Composite post-partum placental-related complications (manual lysis of placenta, revision of uterine cavity, haemoglobin drop ≥3 g/dl, post-partum haemorrhage, need for blood transfusion) were more prevalent in both the PGT and IVF-ICSI groups as opposed to naturally conceived (20.0% versus 18.9% versus 10.3%, respectively, P < 0.001, P = 0.007). In a multivariate regression model PGT was not found to be independently associated with composite post-partum placental-related complications (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 0.83-2.15), while IVF-ICSI pregnancies had increased risk (aOR 1.52, 95% CI 1.20-1.97) compared with natural conception. No difference was found between fresh and frozen cycles or between day 3 and day 5 embryo transfer. CONCLUSIONS: PGT pregnancies have a comparable risk of post-partum placental-related complications to naturally conceived pregnancies, unlike IVF-ICSI pregnancies. It is possible that infertility itself is the main mediator for post-partum complications in IVF-ICSI pregnancies.

Comparison of pregnancy rates in antagonist cycles after luteal support with GnRH-agonist versus progesterone: prospective randomized study.

PURPOSE: To compare pregnancy rates in GnRH-antagonist cycles triggered with hCG after luteal phase support with intranasal GnRH-agonist as sole luteal phase support versus standard vaginal progesterone preparation. METHODS: Prospective randomized controlled study of patients who underwent antagonist-based IVF cycles triggered with hCG at university-affiliated tertiary medical center between 2020 and 2022. Patients meeting the inclusion criteria were randomly assigned to either intranasal GnRH-agonist or vaginal progesterone for luteal phase support. Pregnancy rates were the main outcome compared between the two study groups. RESULTS: A total of 150 patients underwent 164 cycles, 127 cycles of which were included in the study cohort. Of them, 64 (50.4%) and 63 (49.6%) cycles were treated with GnRH-agonist or progesterone, respectively, as sole luteal phase support. A significantly higher pregnancy rate was demonstrated in the GnRH-agonist group compared with the progesterone group. After adjustment of several potential confounders such as age, body mass index, past obstetric history, number of IVF cycles, oocyte retrieved and embryos transferred, GnRH-agonist was still associated with a higher pregnancy rate (odds ratio 3.4, 95% confidence interval 1.4-8.3). Ovarian hyperstimulation syndrome rates were similar between the groups. CONCLUSIONS: This prospective study suggests that nasal GnRH-agonist for luteal phase support is associated with higher pregnancy rates compared with standard progesterone support in an antagonist-based protocol triggered with hCG, while maintaining a similar safety profile. TRIAL REGISTRATION: Clinicaltrials.gov NCT05484193. Date of registration: August 02 2022. The trial was retrospectively registered.

Pigment epithelium-derived factor negates oxidative stress in mouse oocytes.

Molecular changes, caused by various environmental factors, affect the quality and developmental potential of oocytes. Oxidative stress (OS) is a major factor involved in various gynecologic disorders and/or in aging. Recent studies suggest that elevated reactive oxygen species (ROS) hamper oocyte quality and future embryonic development. Pigment epithelium-derived factor (PEDF) is a pleiotropic protein, known for its antiangiogenic, anti-inflammatory, and antioxidative properties. Our previous findings demonstrate the antioxidative role of rPEDF in maintaining granulosa cell viability. In the current study, we examined the ability of PEDF to negate the adverse impact of OS on oocytes. Maturation rate of oocytes exposed to OS was significantly lower than that of control oocytes. The number of mtDNA copies in OS-exposed oocytes was significantly higher than in control oocytes (>3 times), whereas ATP concentration was significantly lower. Oocytes exposed to OS demonstrated impaired chromosome arrangement at the metaphase plate. PEDF significantly improved maturation rate of untreated OS-exposed oocytes. Moreover, mtDNA copy number, ATP concentration, and chromosome arrangement at the metaphase plate in rPEDF-treated OS-exposed oocytes were restored to the level of control oocytes. Our findings demonstrate that OS hampers the ability of oocytes to undergo proper in vitro maturation. The energetic balance of OS-exposed oocyte is characterized by excessive mtDNA replication and reduced ATP concentration; it hampers the ability of oocytes to perform high fidelity chromosome segregation. PEDF alleviates this damage, improves the rate of oocyte maturation, and preserves mtDNA level and ATP content, thus enabling oocytes to form proper metaphase plate and improve oocyte competence.

GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch.

BACKGROUND: G protein-coupled receptors (GPCRs) usually regulate cellular processes via activation of intracellular signaling pathways. However, we have previously shown that in several cell lines, GqPCRs induce immediate inactivation of the AKT pathway, which leads to JNK-dependent apoptosis. This apoptosis-inducing AKT inactivation is essential for physiological functions of several GqPCRs, including those for PGF2α and GnRH. METHODS: Here we used kinase activity assays of PI3K and followed phosphorylation state of proteins using specific antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein-protein interactions. Apoptosis was detected by TUNEL assay and PARP1 cleavage. RESULTS: We identified the mechanism that allows the unique stimulated inactivation of AKT and show that the main regulator of this process is the phosphatase PP2A, operating with the non-canonical regulatory subunit IGBP1. In resting cells, an IGBP1-PP2Ac dimer binds to PI3K, dephosphorylates the inhibitory pSer608-p85 of PI3K and thus maintains its high basal activity. Upon GqPCR activation, the PP2Ac-IGBP1 dimer detaches from PI3K and thus allows the inhibitory dephosphorylation. At this stage, the free PP2Ac together with IGBP1 and PP2Aa binds to AKT, causing its dephosphorylation and inactivation. CONCLUSION: Our results show a stimulated shift of PP2Ac from PI3K to AKT termed "PP2A switch" that represses the PI3K/AKT pathway, providing a unique mechanism of GPCR-stimulated dephosphorylation. Video Abstract.

Clinical outcome of planned oocyte cryopreservation at advanced age.

PURPOSE: To report outcome of planned oocyte cryopreservation (POC) in the first 8 years of this treatment in our center. METHODS: A retrospective study in a university-affiliated medical center. RESULTS: A total of 446 women underwent POC during 2011-2018. Fifty-seven (13%) women presented to use these oocytes during the study period (until June 2021). POC was performed at a mean age of 37.9 ± 2.0 (range 33-41). Age at thawing was 43.3 ± 2.1 (range 38-49). A total of 34 (60%) women transferred their oocytes for thawing at other units. Oocyte survival after thawing was significantly higher at our center than following shipping to ancillary sites (78 vs. 63%, p = 0.047). Forty-nine women completed their treatment, either depleting their cryopreserved oocytes without conceiving (36) or attaining a live birth (13)-27% live birth rate per woman. Only one of eleven women who cryopreserved oocytes aged 40 and older had a live birth using thawed oocytes. CONCLUSION: Women should be advised to complete planned oocyte cryopreservation before age 40, given low success rates in women who underwent cryopreservation at advanced reproductive age. In this study, oocyte shipping was associated with lower survival rate. These findings may be relevant for women considering POC and utilization of cryopreserved oocytes.

The Role of PEDF in Reproductive Aging of the Ovary.

Reproductive aging is characterized by a decline in ovarian function and in oocytes' quantity and quality. Pigment epithelium-derived factor (PEDF), a pivotal player in ovarian angiogenic and oxidative balance, was evaluated for its involvement in reproductive aging. Our work examines the initial stage of reproductive aging in women and mice, and the involvement of PEDF in the process. Granulosa cells from reproductively-aged (RA) women and mice (36-44 years old and 9-10 months old, respectively) indicated an increase in the level of PEDF mRNA (qPCR), with yet unchanged levels of AMH and FSHR mRNAs. However, the PEDF protein level in individual women showed an intra-cellular decrease (ELISA), along with a decrease in the corresponding follicular fluid, which reflects the secreted fraction of the protein. The in vitro maturation (IVM) rate in the oocytes of RA mice was lower compared with the oocytes of young mice, demonstrated by a reduced polar body extrusion (PBE) rate. The supplementation of PEDF improved the hampered PBE rate, manifested by a higher number of energetically-competent oocytes (ATP concentration and mtDNA copy number of individual oocytes). Our findings propose PEDF as an early marker of reproductive aging, and a possible therapeutic in vitro agent that could enhance the number of good-quality oocytes in older IVF patients.

Expanded clinical validation of Haploseek for comprehensive preimplantation genetic testing.

PURPOSE: We previously developed Haploseek, a method for comprehensive preimplantation genetic testing (PGT). However, some key features were missing, and the method has not yet been systematically validated. METHODS: We extended Haploseek to incorporate DNA from embryo grandparents and to allow testing of variants on chromosome X or in regions where parents share common haplotypes. We then validated Haploseek on 151 embryo biopsies from 27 clinical PGT cases. We sequenced all biopsies to low coverage (0.2×), and performed single-nucleotide polymorphism (SNP) microarray genotyping on the embryos' parents and siblings/grandparents. We used the extended Haploseek to predict chromosome copy-number variants (CNVs) and relevant variant-flanking haplotypes in each embryo. We validated haplotype predictions for each clinical sample against polymerase chain reaction (PCR)-based PGT case results, and CNV predictions against established commercial kits. RESULTS: For each of the 151 embryo biopsies, all Haploseek-derived haplotypes and CNVs were concordant with clinical PGT results. The cases included 17 autosomal dominant, 5 autosomal recessive, and 3 X-linked monogenic disorders. In addition, we evaluated 1 Robertsonian and 2 reciprocal translocations, and 17 cases of chromosome copy-number counting were performed. CONCLUSION: Our results demonstrate that Haploseek is clinically accurate and fit for all standard clinical PGT applications.

Pigment epithelium derived factor as a novel multi-target treatment for uterine fibroids.

RESEARCH QUESTION: Does recombinant pigment epithelium derived factor (PEDF) have potential in treating uterine fibroids? DESIGN: In-vitro models that used human leiomyoma and Eker rat uterine leiomyoma (ELT-3) cell lines. The ELT-3 cell line was used to examine cellular targets after adding recombinant PEDF to the culture media. Athymic nude female mice were used as an in-vivo model. They were injected with ELT-3 cells to induce ectopic fibroid lesions, then treated with recombinant PEDF. RESULTS: RNA expression of PEDF and its receptors was found in both leiomyoma cell lines, as well as the expression of PEDF receptors. Addition of recombinant PEDF to the culture medium of leiomyoma cell lines activated ERK in a time-dependent manner, induced down-regulation of vascular endothelial growth factor mRNA and protein, as well as the mRNAs of oestrogen receptors alpha and beta and inhibited cellular proliferation. Treatment of mice-bearing fibroids with recombinant PEDF reduced fibroid growth rate and resulted in smaller tumours. CONCLUSIONS: This study suggests that recombinant PEDF is a putative novel potent physiological treatment for uterine fibroids. It targets several cornerstones of fibroid pathobiology in parallel, including vascular endothelial growth factor and oestrogen receptors, which are needed for vascularization, and restricts fibroid growth and final size in an animal model.

Gq-Induced Apoptosis is Mediated by AKT Inhibition That Leads to PKC-Induced JNK Activation.

BACKGROUND/AIMS: Gq protein-coupled receptors (GqPCRs) regulate various cellular processes including mainly proliferation and differentiation. In a previous study, we found that in prostate cancer cells, the GqPCR of GnRH induces apoptosis by reducing the PKC-dependent AKT activity and elevating JNK phosphorylation. Since it was thought that GqPCR induces mainly activation of AKT, we undertook to examine how general is this phenomenon and understand its signaling. METHODS: We used various cells to follow the phosphorylation of signaling components using western blotting. RESULTS: In a screen of 21 cell lines, we found that PKC activation results in the reduction of AKT activity, which correlates nicely to JNK activation and in some cases to apoptosis. To further understand the signaling pathways involved in this stimulation, we studied in detail the SVOG-4O and αT3-1 cells. We found that PGF2α and GnRH agonist (GnRH-a) indeed induce significant Gq- and PKC- dependent apoptosis in these cells. This is mediated by two signaling branches downstream of PKC, which converge at the level of MLK3 upstream of JNK. One branch consists on c-Src activation of the JNK cascade and the second involves reduction of AKT activity that alleviates its inhibitory effect on MLK3, to allow the flow of the c-Src signal to JNK. At the MAPKK level, we found that the signal is transmitted by MKK7 and not MKK4. CONCLUSION: Our results present a general mechanism that mediates a GqPCR-induced, death receptors-independent, apoptosis in physiological, as well as cancer-related systems.

Termination of pregnancy due to renal tract abnormalities: survey of 97 fetuses from a single medical center.

OBJECTIVE: The article aimed to assess the spectrum of fetal renal tract abnormalities as a major finding leading to termination of pregnancy (TOP). METHOD: The study population included all pregnant women with singleton pregnancy who underwent TOP in our institute because of fetal renal tract indications between 1998 and 2015. We specifically excluded TOPs performed because of multiple pregnancies, multisystem defects, abnormal karyotype and chromosomal or genetic defect not related to renal tract abnormalities. The patients were stratified into late TOP (≥24 weeks' gestation) and early TOP (<24 weeks' gestation). RESULTS: There were 97 (3.5%) cases of TOP because of fetal renal abnormalities and are the subjects of this study. Of these cases, 19 (19.6%) were at ≥24 weeks' gestation. Renal cystic disease was the leading indication for late TOP compared with early TOP group (31.8% vs 21.8%, respectively, p = 0.001). Routine prenatal care raised suspicion of abnormalities in 11 (50.9%) cases, and diagnosis was established by additional tests. Abnormal findings were either missed in one (5.3%) case or developed later in two (10.5%) cases. No routine prenatal screening was performed in the remaining five (26.3%) cases. CONCLUSIONS: We found a different distribution for fetal renal tract abnormalities leading to late versus early TOP. As many of renal tract malformations could have been diagnosed earlier (~32%), timely scanning may reduce the need for late TOPs in some cases. © 2016 John Wiley & Sons, Ltd.

Pigment epithelium-derived factor regulation by human chorionic gonadotropin in granulosa cells.

Human chorionic gonadotropin (hCG) is a known trigger of ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication of assisted reproduction. Administration of hCG results in the release of vascular endothelial growth factor (VEGF) from the ovary. We have previously shown that expression of pigment epithelium-derived factor (PEDF) in granulosa cell line is regulated by hCG, reciprocally to VEGF, and that the PEDF-VEGF balance is impaired in OHSS. Our aim was to explore the signaling network by which hCG downregulates the expression of PEDF mRNA and protein in granulosa cells. We applied specific chemical inhibitors and stimuli to human primary granulosa cells and rat granulosa cell line. We found that PKA and protein kinase C, as well as EGFR, ERK1/2 and PI3K, participate in the signaling network. The finding that hCG-induced PEDF downregulation and VEGF upregulation are mediated by similar signaling cascades emphasizes the delicate regulation of ovarian angiogenesis.

Infertility Following Retained Products of Conception: Does the Timing of Surgical Intervention Matter?

BACKGROUND: Despite the large volume of evidence on the management of retained products of conception (RPOC), there are virtually no data regarding the optimal time frame of surgical intervention in case of RPOC. OBJECTIVES: To examine whether the time interval between spontaneous vaginal delivery or pregnancy termination and the uterine evacuation due to pathologically confirmed RPOC influences the reproductive outcome. METHODS: We retrospectively reviewed all the records of women who were admitted to our department due to pathologically confirmed RPOC following either spontaneous vaginal delivery or pregnancy termination between January 2000 and December 2010. Based on the median time from delivery or pregnancy termination until the operative intervention in the study group, patients were stratified into two groups: early intervention (< 3 weeks) and late intervention (> 3 weeks). Reproductive outcomes were compared between the two study groups. RESULTS: Reproductive outcomes were analyzed in 172 patients with pathologically confirmed RPOC. Of them, 95 (55.2%) were included in the early intervention group and 77 (44.8%) in the late intervention group. There were no significant differences in the conception rate, mean time to conception, and the occurrence rate of a new infertility problem in women with early surgical intervention compared to those with late surgical intervention (P > 0.05). Furthermore, there was no significant difference between the groups in the pregnancy outcomes following RPOC. CONCLUSIONS: Early surgical intervention in women with pathologically confirmed RPOC following spontaneous vaginal delivery or pregnancy termination yields the same reproductive outcomes as late surgical intervention.

The association of crown-rump length discrepancy with birthweight discordance in spontaneous versus IVF monochorionic twins: a multicenter study.

OBJECTIVE: The objective of this study was to compare the associations of crown-rump length (CRL) discrepancy with birthweight discordance in spontaneous versus in vitro fertilization (IVF) monochorionic (MC) twin pregnancies. METHOD: This is a multicenter retrospective study on women with twin pregnancies assessed for nuchal translucency between January 1997 and July 2013. The study group was subdivided into MC twins conceived spontaneously and after IVF. Pregnancies with later fetal death or twin transfusion syndrome were excluded. A large-weight discordance was defined as a difference of birthweights of >15%. RESULTS: The study group included 171 pregnancies; of them, 142 (83%) were spontaneous and 29 (17%) were IVF conceived. In the entire cohort, we found a significant correlation between birthweight discordance and CRL discrepancy (r = 0.173, P < 0.05). While a significant correlation was found between CRL discrepancy and birthweight discordance in spontaneous-conceived pregnancies (n = 142, r = 0.24, P = 0.005), such correlation was not present in IVF pregnancies (n = 29, r = -0.7, P = 0.724). A logistic regression analysis found significant odds of larger-weight discordance for each increase of 1% in CRL discrepancy among spontaneously conceived pregnancies (odds ratio = 1.1, confidence interval = 1.03-1.2, P = 0.005). A receiver operating characteristic (ROC) for large-weight discordance in the spontaneously conceived pregnancies demonstrated an area under the ROC curve of 0.613 (P = 0.039). CONCLUSION: The significant correlation between CRL discrepancy and birthweight discordance in spontaneous versus IVF MC twin pregnancies might suggest differential monozygotic twinning process.

Comparison of Reproductive Outcomes following Retained Products of Conception after Vaginal Delivery versus First-Trimester Abortion.

OBJECTIVE: To compare the reproductive outcomes of women with pathologically confirmed retained products of conception (RPOC) following spontaneous vaginal delivery versus first-trimester pregnancy termination. METHODS: We retrospectively reviewed all cases of women who underwent uterine re-evacuation due to pathologically confirmed RPOC between January 1, 2000 and December 31, 2010. Reproductive outcomes were compared between women with RPOC following spontaneous vaginal delivery and those who underwent dilatation and curettage (D&C) due to first-trimester abortion. RESULTS: The study group consisted of 176 patients with pathologically confirmed RPOC. Of those, 83 (47.1%) were admitted after spontaneous vaginal delivery and 93 (52.9%) following D&C due to first-trimester abortion. There were no significant differences in the conception rate, the mean time to conception and the rate of a new infertility problem between women with RPOC after vaginal delivery compared to those following pregnancy termination (p > 0.05). Furthermore, there were no significant differences between the groups in pregnancy outcomes following RPOC. CONCLUSION: Pathologically confirmed RPOC harbors the same reproductive outcomes following spontaneous vaginal delivery and first-trimester pregnancy termination.

Ploidy of spermatogenic cells of men with non-mosaic Klinefelter's syndrome as measured by a computerized cell scanning system.

PURPOSE: This study aims to characterize the origin of testicular post-meiotic cells in non-mosaic Klinefelter's syndrome (KS). METHODS: The study included testicular tissue specimens from 11 non-mosaic KS patients, with (6 positive) and without (5 negative) spermatozoa presence. The obtained testicular cells were affixed and stained for morphology followed by fluorescence in situ hybridization (FISH) for centromeric probes X, Y, and 18. We used a computerized automated cell scanning system that enables simultaneous viewing of morphology and FISH in the same cell. RESULTS: A total of 12,387 cells from the positive cases, 11,991 cells from the negative cases, and 1,711 cells from the controls were analyzed. The majority of spermatogonia were 47, XXY in both the positive and negative KS cases (88.9 ± 4.76 % and 90.6 ± 4.58 %) as were primary spermatocytes (76.8 ± 8.14 % and 79.6 ± 7.30 %). The respective rates of secondary spermatocytes and post-meiotic cells (round, elongating spermatids and sperm cells) were 1.1 ± 1.39 % in the positive cases, 2.9 ± 3.33 % in the negative cases, compared to 67.6 ± 6.22 % in the controls (P < 0.02). Pairing of both 18 and XY homologous chromosomes in 46,XY primary spermatocytes was 2.5 ± 2.31 % and 3.4 ± 2.39 %, respectively, compared to 19.8 ± 8.95 % in the control group (P < 0.02) and in 47,XXY primary spermatocytes in 2.4 ± 3.8 % in the positive group and 3.2 ± 2.26 % in the negative group. CONCLUSIONS: This study presents data to indicate that the majority of primary spermatocytes in the testes of non-mosaic KS patients are 47,XXY and could possibly develop into post-meiotic cells.

Role of pigment epithelium-derived factor in the reproductive system.

The physiological function of the female reproductive organs is hormonally controlled. In each cycle, the reproductive organs undergo tissue modifications that are accompanied by formation and destruction of blood vessels. Proper angiogenesis requires an accurate balance between stimulatory and inhibitory signals, provided by pro- and anti-angiogenic factors. As with many other tissues, vascular endothelial growth factor (VEGF) appears to be one of the major pro-angiogenic factors in the female reproductive organs. Pigment epithelium-derived factor (PEDF) is a non-inhibitory member of the serine protease inhibitors (serpin) superfamily, possessing potent physiologic anti-angiogenic activity that negates VEGF activity. The role of PEDF in decreasing abnormal neovascularization by exerting its anti-angiogenic effect that inhibits pro-angiogenic factors, including VEGF, has been investigated mainly in the eye and in cancer. This review summarizes the function of PEDF in the reproductive system, showing its hormonal regulation and its anti-angiogenic activity. Furthermore, some pathologies of the female reproductive organs, including endometriosis, ovarian hyperstimulation syndrome, polycystic ovary syndrome, and others, are associated with a faulty angiogenic process. This review illuminates the role of PEDF in their pathogenesis and treatment. Collectively, we can conclude that although PEDF seems to play an essential role in the physiology and pathophysiology of the reproductive system, its full role and mechanism of action still need to be elucidated.

The association of crown-rump length discrepancy with birthweight discordance in spontaneous versus assisted conception dichorionic twins.

OBJECTIVE: This study aimed to compare the associations of crown-rump length (CRL) discrepancy with birthweight discordance in spontaneous versus vitro fertilization (IVF) conceived dichorionic twin pregnancies. METHOD: A computerized retrospective study of women referred to our ultrasonographic unit for nuchal translucency examination between January 1997 and December 2011. The study group was subdivided into twins conceived after IVF, non-IVF fertility treatment and spontaneously conceived twins. Birthweight discordance was defined as a difference of birthweights of >20%. RESULTS: A total of 688 dichorionic twin pregnancies were included, all of them ending in live birth of both twins. IVF-conceived pregnancies were associated with a significant increased risk of extreme birthweight discordance compared with spontaneous-conceived twin pregnancies (OR = 2.3; CI = 1.4-3.8, P < 0.001). A significant correlation was found between CRL discrepancy and birthweight discordance in spontaneous-conceived pregnancies (r = 0.15, P < 0.05). In contrast, there was no significant correlation between CRL discrepancy and birthweight discordance in both IVF and fertility treatment-conceived pregnancies. CONCLUSION: Because birthweight discordance in IVF-conceived twins did not correlate with CRL discrepancy, we assume that it emerges later in pregnancy, maybe related to maternal underplaying complications, for which IVF was indicated in the first place.

Intercoat (Oxiplex/AP gel) for preventing intrauterine adhesions after operative hysteroscopy for suspected retained products of conception: double-blind, prospective, randomized pilot study.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of Oxiplex/AP gel (Intercoat) in reducing intrauterine adhesion formation after hysteroscopic treatment because of retained products of conception (RPOC). DESIGN: Prospective double-blind, randomized, controlled pilot study (Canadian Task Force classification I). SETTING: Tertiary medical center. PATIENTS: All women who underwent hysteroscopic treatment because of RPOC at our institution between September 2009 and June 2012 were invited to participate. After operative hysteroscopy, participants were randomized to either have their uterine cavity filled with Oxiplex/AP gel (study group, n = 26) or not (control group, n = 26). INTERVENTIONS: Diagnostic office hysteroscopy to assess for adhesion formation was performed after 6 to 8 weeks. Findings were graded according to the American Fertility Society classification. Rates of subsequent pregnancy in the 2 groups were assessed. MEASUREMENTS AND MAIN RESULTS: Intraoperative complication rates were similar between the 2 groups. There were no postoperative complications after Oxiplex/AP gel application. Moderate to severe adhesions developed in 1 woman (4%) in the study group and 3 (14%) in the control group (p = .80). During follow-up of 20 months (range, 2-33 months), 7 women (27%) in the treatment group conceived, compared with 3 (14%) in the control group (p = .50). CONCLUSION: Intrauterine application of Oxiplex/AP gel after hysteroscopic removal of RPOC is safe. In this small sample, the difference in the rate of intrauterine adhesions was not statistically significant. A larger study would enable further establishment of the safety and efficacy of use of this gel.

IVF outcomes pre- and post-anti-COVID-19 vaccination - Are there any differences?

Since the beginning of the SARS-CoV-2 pandemic, there have been rising concerns about the virus's possible ability to affect male and female fertility. Although effective vaccines were introduced and the vaccination rate of the general population is high, some reproductive-age individuals are still hesitant to receive the vaccine, because of an unestablished belief that the vaccine might impair fertility. In this single-center retrospective study, encompassing data from 387 medical files of in-vitro fertilization (IVF) patients we compared IVF cycle outcomes and sperm characteristics in vaccinated couples before and after vaccination, as well as between vaccinated patients and a control group of individuals who were neither vaccinated nor infected with COVID-19 before or during the cycles. We found no significant differences between vaccinated and non-vaccinated patients concerning the number of retrieved oocytes and the total motile sperm count (TMC). The mean number of retrieved oocytes showed a slight increase in the vaccinated group compared to the non-vaccinated control group (10.8 vs. 9.18, p = 0.14). Additionally, within the vaccinated group, no significant difference was observed in the mean number of oocytes before and after vaccination (9.7 and 10.8, p = 0.14). Other similar cycle outcomes between the groups were the rates of implantation, pregnancy, and ovarian hyperstimulation syndrome. This study emphasized that the mRNA anti-COVID-19 vaccination doesn't adversely affect ovarian response or sperm quality in IVF patients. These findings contribute valuable insights to the safety profile of anti-COVID-19 vaccines in the context of reproductive-aged populations, aiding decision-making during ongoing virus outbreaks and potential future scenarios.