PABPN1 functions as a hub in the assembly of nuclear poly(A) domains that are essential for mouse oocyte development.

Growing oocytes store a large amount of maternal mRNA to support the subsequent "maternal-zygotic transition" process. At present, it is not clear how the growing oocytes store and process the newly transcribed mRNA under physiological conditions. In this study, we report non-membrane-bound compartments, nuclear poly(A) domains (NPADs), as the hub for newly transcribed mRNA, in developing mouse oocytes. The RNA binding protein PABPN1 promotes the formation of NPAD through its N-terminal disordered domain and RNA-recognized motif by means of liquid phase separation. Pabpn1-null growing oocytes cannot form NPAD normally in vivo and have defects in stability of oocyte growing-related transcripts and formation of long 3' untranslated region isoform transcripts. Ultimately, Pabpn1fl/fl;Gdf9-Cre mice are completely sterile with primary ovarian insufficiency. These results demonstrate that NPAD formed by the phase separation properties of PABPN1-mRNA are the hub of the newly transcribed mRNA and essential for the development of oocytes and female reproduction.

A novel solution for freezing individual spermatozoa using a right angular cryopiece embedded in a grooved petri dish.

Herein, we introduced a novel individual sperm freezing device named SpermCD, which consists of a right angular cryopiece (RA-Cryopiece, or "C") and a grooved petri dish ("D"). SpermCD allows embryologists to transfer sperm and perform ICSI on the same focal plane. Thirty-five patients underwent single sperm cryopreservation using SpermCD, including four patients with non-obstructive azoospermia (NOA), 14 patients with virtual azoospermia and 17 patients with cryptozoospermia. One hundred and twenty-five cryopreserved spermatozoa from nine patients were thawed on the day of the oocyte retrieval and 121 spermatozoa were found, with a sperm recovery rate of 97.1 ± 4.6%. Sixty-five MII oocytes from their spouse were injected with thawed sperm. Normal fertilization and high-quality embryo rates were 68.0% ± 33.2% and 24.4% ± 22.2%. Nineteen transplantable embryos were formed after fertilization with frozen sperm, eight of which were transplanted in five couples, resulting in four successful deliveries. SpermCD is a simple and practical individual sperm freezing device.

NAT10-mediated N4-acetylcytidine modification is required for meiosis entry and progression in male germ cells.

Post-transcriptional RNA modifications critically regulate various biological processes. N4-acetylcytidine (ac4C) is an epi-transcriptome, which is highly conserved in all species. However, the in vivo physiological functions and regulatory mechanisms of ac4C remain poorly understood, particularly in mammals. In this study, we demonstrate that the only known ac4C writer, N-acetyltransferase 10 (NAT10), plays an essential role in male reproduction. We identified the occurrence of ac4C in the mRNAs of mouse tissues and showed that ac4C undergoes dynamic changes during spermatogenesis. Germ cell-specific ablation of Nat10 severely inhibits meiotic entry and leads to defects in homologous chromosome synapsis, meiotic recombination and repair of DNA double-strand breaks during meiosis. Transcriptomic profiling revealed dysregulation of functional genes in meiotic prophase I after Nat10 deletion. These findings highlight the crucial physiological functions of ac4C modifications in male spermatogenesis and expand our understanding of its role in the regulation of specific physiological processes in vivo.

Preimplantation genetic testing for aneuploidy in severe male factor infertility: protocol for a multicenter randomised controlled trial.

INTRODUCTION: Conventional intracytoplasmic sperm injection (ICSI) is a widely used treatment for couples with severe male infertility. However, there are controversies regarding the selection and the damage to gametes during the ICSI procedure. Although preimplantation genetic testing for aneuploidies (PGT-A) can give genetic information about embryos for transfer and improve fertility rate, and it is widely used in women with recurrent spontaneous abortion or advanced age, PGT-A is not only more expensive but also has unclear effectiveness with respect to the improvement of fertility rate among couples with severe male infertility. High-quality, well-powered randomised clinical trials (RCTs) comparing ICSI+PGT-A and ICSI are lacking. METHODS AND ANALYSIS: This is a protocol for a multicenter, open-label RCT in four reproductive medical centers qualified for PGT technique in China. We will study couples with severe male infertility scheduled for their fertility treatment. After the blastocyst culture, eligible participants are randomised to the ICSI+PGT-A group or the conventional ICSI group in a 1:1 ratio. Other assisted reproductive procedures are similar and parallel between the two groups. The primary outcome will be live birth rate and cumulative live-birth rate . Secondary outcomes will be embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, spontaneous abortion rate, ongoing pregnancy rate, preterm birth rate, fetal chromosomal abnormality rate, birth defect rate and treatment complications. To demonstrate or refute a difference between the two groups, we plan to include 188 participants in each group; taking consideration of 20% of dropout, the total target sample size is 450. ETHICS AND DISSEMINATION: Ethical approval was obtained from International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University Medical Science Research Ethics Committee (GKLW2016-16). Informed consent will be obtained from each participant. The findings will be disseminated to the public through conference presentations and publication in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT02941965.

Are testicular sperms superior to ejaculated sperms in couples with previous ART failure due to high rate of fragmented embryos? A retrospective cohort study.

Objective: The aim was to clarify whether using testicular sperm reduces embryo fragmentation and improves cycle outcomes. Methods: Fragmented embryo was defined as an embryo in which fragments account for more than one third of the embryonic surface area. High rate of fragmented embryos was defined by a proportion of fragmented embryos higher than 50%. We recruited infertile couples who had undergone at least one ovarian stimulation cycle using ejaculated sperm but failed to conceive due to high rate of fragmented embryos in each previous cycle. After fully informed consent, the couples agreed to obtain testicular sperm by testicular puncture and use testicular sperm for intracytoplasmic sperm injection (ICSI). The normal fertilization rate, transferable embryo rate, fragmented embryo rate and cycle outcomes were compared between ejaculated sperm group (EJA-sperm group) and testicular sperm group (TESTI-sperm group). Results: Twenty-two couples who agreed to participate in our study underwent 32 ICSI cycles with ejaculated spermatozoa and 23 ICSI cycles with testicular spermatozoa. Embryo transfers were cancelled in 8 ejaculated cycles and 4 testicular cycles because of no transferable embryos. There were no significant differences in age, normal fertilization rate and high-quality embryo rate between ejaculated and testicular groups. The transferable embryo rate and implantation rate in TESTI-sperm group were significantly higher than those in EJA-sperm group (36.9% vs. 22.0%, p < 0.01; 34.2% vs. 0%, p < 0.001). The fragmented embryo rate in TESTI-sperm group was significantly lower than that in EJA-sperm group (61.2% vs. 75.7%, p < 0.05). Conclusion: Our small retrospective cohort study suggests that using testicular sperm may be a recommended option for couples with previous ART failure because of high rate of fragmented embryos. Large samples, multicenter studies or randomized controlled trial (RCT) are needed to further confirm the superiority of testicular sperm.

Factors associated with the incidence of ectopic pregnancy in women undergoing assisted reproductive treatment.

BACKGROUND: Ectopic pregnancy (EP) is a common complication in women undergoing assisted reproductive treatment, but the underlying causes for this remain unclear. This study aimed to explore factors affecting the incidence of EP in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: This was a retrospective study on the incidence of EP in IVF/ICSI cycles between January 1, 2013 and December 31, 2017. Patient age, infertility diagnosis (tubal factor or not), primary or secondary infertility, type of cycle (frozen-thawed or fresh), type of embryo(s) transferred (cleavage embryo or blastocyst), number of embryos transferred (one, two, or three), previous history of EP, and endometrial combined thickness were analyzed to explore their relationships with the incidence of EP. Based on clinical typing results, the patients were divided into an EP group or a non-EP group. Categorical variables were analyzed using Chi-squared test or Fisher exact test. Logistic regression analysis was performed to explore their associations with the incidence of EP. RESULTS: The percentage of patients with primary infertility in EP group was significantly lower than that in non-EP group (31.3% vs. 46.7%, χ = 26.032, P < 0.001). The percentage of patients with tubal infertility in EP group was also significantly higher than that in non-EP group (89.2% vs. 63.6%, χ = 77.410, P < 0.001). The percentages of patients with transfer of cleavage-stage embryo or blastocyst (91.4% vs. 84.4%, χ = 10.132, P = 0.001) and different endometrial combined thickness (ECT) (χ = 18.373, P < 0.001) differed significantly between EP and non-EP groups. For patients who had a previous history of one to four EPs, the percentage of patients undergoing transfer of a cleavage-stage embryo was significantly higher in EP group than that in non-EP group (92.2% vs. 77.6%, χ = 13.737, P < 0.001). In multivariate logistic regression analysis, tubal infertility was strongly associated with EP (adjusted odds ratio: 3.995, 95% confidence interval: 2.706-5.897, P < 0.001). CONCLUSIONS: In IVF/ICSI cycles, transfer of a blastocyst-stage embryo, especially for patients with a previous history of EP, reduced the rate of EP. Tubal infertility was strongly associated with EP.

NLRP3 inflammasome: a new therapeutic target for high-risk reproductive disorders?

ABSTRACT: The NOD-like receptor protein 3 (NLRP3) inflammasome is a key regulator of the host's immune response, and many immune and metabolic disorders are linked to its activation. This review aimed to investigate and clarify the relationship between this inflammasome and high-risk reproductive disorders. Papers cited here were retrieved from PubMed up to August 2020 using the keywords "NLRP3" or "NALP3", "caspase-1", "endometriosis", "gestational diabetes", "interleukin (IL)-18", "IL-1ß", "pre-eclampsia (PE)", "preterm birth", "polycystic ovarian syndrome (PCOS)", "recurrent spontaneous abortion (RSA)", and combinations of these terms. The results show that NLRP3 inflammasome is associated with various high-risk reproductive disorders and many inflammatory factors are secreted during its activation, such as IL-1ß induced during the development of endometriosis. PCOS is also associated with activation of the NLRP3 inflammasome, especially in overweight patients. It also participates in the pathogenesis of RSA and is activated in fetal membranes before preterm birth. The placentas of pregnant women with PE show higher expression of the NLRP3 inflammasome, and gestational diabetes mellitus occurs simultaneously with its activation. Current evidence suggest that the NLRP3 inflammasome plays an important role in female reproductive disorders. New treatment and management methods targeting it might help reduce the incidence of such disorders and improve neonatal outcomes.

The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation.

Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of oocyte survival and meiotic cell cycle progression. DCAF13, a novel CRL4 adaptor, is essential for oocyte development. But the mechanisms by which CRL4-DCAF13 supports meiotic maturation remained unclear. In this study, we demonstrated that DCAF13 stimulates the meiotic resumption-coupled activation of protein synthesis in oocytes, partially by maintaining the activity of PI3K signaling pathway. CRL4-DCAF13 targets the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation. Dcaf13 knockout in oocytes caused decreased CDK1 activity and impaired meiotic cell cycle progression and chromosome condensation defects. As a result, chromosomes fail to be aligned at the spindle equatorial plate, the spindle assembly checkpoint is activated, and most Dcaf13 null oocytes are arrested at the prometaphase I. The DCAF13-dependent PTEN degradation mechanism fits in as a missing link between CRL4 ubiquitin E3 ligase and PI3K pathway, both of which are crucial for translational activation during oocyte GV-MII transition.

Mammalian nucleolar protein DCAF13 is essential for ovarian follicle maintenance and oocyte growth by mediating rRNA processing.

During mammalian oocyte growth, chromatin configuration transition from the nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) type plays a key role in the regulation of gene expression and acquisition of meiotic and developmental competence by the oocyte. Nonetheless, the mechanism underlying chromatin configuration maturation in oocytes is poorly understood. Here we show that nucleolar protein DCAF13 is an important component of the ribosomal RNA (rRNA)-processing complex and is essential for oocyte NSN-SN transition in mice. A conditional knockout of Dcaf13 in oocytes led to the arrest of oocyte development in the NSN configuration, follicular atresia, premature ovarian failure, and female sterility. The DCAF13 deficiency resulted in pre-rRNA accumulation in oocytes, whereas the total mRNA level was not altered. Further exploration showed that DCAF13 participated in the 18S rRNA processing in growing oocytes. The lack of 18S rRNA because of DCAF13 deletion caused a ribosome assembly disorder and then reduced global protein synthesis. DCAF13 interacted with a protein of the core box C/D ribonucleoprotein, fibrillarin, i.e., a factor of early pre-rRNA processing. When fibrillarin was knocked down in the oocytes from primary follicles, follicle development was inhibited as well, indicating that an rRNA processing defect in the oocyte indeed stunts chromatin configuration transition and follicle development. Taken together, these results elucidated the in vivo function of novel nucleolar protein DCAF13 in maintaining mammalian oogenesis.

CNOT6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte.

Meiotic resumption-coupled degradation of maternal transcripts occurs during oocyte maturation in the absence of mRNA transcription. The CCR4-NOT complex has been identified as the main eukaryotic mRNA deadenylase. In vivo functional and mechanistic information regarding its multiple subunits remains insufficient. Cnot6l, one of four genes encoding CCR4-NOT catalytic subunits, is preferentially expressed in mouse oocytes. Genetic deletion of Cnot6l impaired deadenylation and degradation of a subset of maternal mRNAs during oocyte maturation. Overtranslation of these undegraded mRNAs caused microtubule-chromosome organization defects, which led to activation of spindle assembly checkpoint and meiotic cell cycle arrest at prometaphase. Consequently, Cnot6l-/- female mice were severely subfertile. The function of CNOT6L in maturing oocytes is mediated by RNA-binding protein ZFP36L2, not maternal-to-zygotic transition licensing factor BTG4, which interacts with catalytic subunits CNOT7 and CNOT8 of CCR4-NOT Thus, recruitment of different adaptors by different catalytic subunits ensures stage-specific degradation of maternal mRNAs by CCR4-NOT This study provides the first direct genetic evidence that CCR4-NOT-dependent and particularly CNOT6L-dependent decay of selective maternal mRNAs is a prerequisite for meiotic maturation of oocytes.

CFP1 coordinates histone H3 lysine-4 trimethylation and meiotic cell cycle progression in mouse oocytes.

Trimethylation of histone H3 on lysine-4 (H3K4me3) is associated with gene-regulatory elements, but its transcription-independent function in cell division is unclear. CxxC-finger protein-1 (CFP1) is a major mediator of H3K4 trimethylation in mouse oocytes. Here we report that oocyte-specific knockout of Cxxc1, inhibition of CFP1 function, or abrogation of H3K4 methylation in oocytes each causes a delay of meiotic resumption as well as metaphase I arrest owing to defective spindle assembly and chromosome misalignment. These phenomena are partially attributed to insufficient phosphorylation of histone H3 at threonine-3. CDK1 triggers cell division-coupled degradation and inhibitory phosphorylation of CFP1. Preventing CFP1 degradation and phosphorylation causes CFP1 accumulation on chromosomes and impairs meiotic maturation and preimplantation embryo development. Therefore, CFP1-mediated H3K4 trimethylation provides 3a permission signal for the G2-M transition. Dual inhibition of CFP1 removes the SETD1-CFP1 complex from chromatin and ensures appropriate chromosome configuration changes during meiosis and mitosis.

Transforming growth factor beta1 from endometriomas promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling.

To elucidate whether the endometriotic cells of endometriomas synthesize transforming growth factor beta1 (TGF-beta1) and understand how it affects surrounding ovarian tissue. We collected biopsies of the cystic walls from 42 endometriomas and 29 mature teratomas and compared mRNA and protein expression of fibrosis-related factors between the cystic walls. Then we detected TGFB1 mRNA synthesis in endometriomas, and tested TGF-beta1 fibrotic effect in vitro. Moreover, we verified the expression of Smad2/3 signaling components in the endometriotic cystic wall in order to understand whether TGF-beta1/Smad signaling is involved in fibrosis formation of the tissue surrounding endometriomas. The cystic walls from endometriomas demonstrated severe adhesion to ovarian tissue and obvious fibrosis compared with the mature teratomas, which was proven by the increased mRNA expression of fibrotic markers. Additionally, TGFB1 was obviously expressed in the endometriotic cystic wall, and total TGFB1 protein was significantly higher in the cystic walls of endometriomas than mature teratomas. Interestingly, TGFB1 mRNA was confirmed to be specifically synthesized in the endometriotic loci through fluorescence in situ hybridization. Cultured endometriomas derived stromal cells showed obvious fibrosis after exposed to TGF-beta1. Furthermore, components of the TGF-beta1/Smad pathway such as Smad2, Smad3, Smad4, and their phosphorylated forms were also expressed in the same location as TGF-beta1, TGF-beta receptor1, and fibrotic factors expressed in the endometriotic cystic walls. In summary, endometriotic cells of endometriomas synthesize TGF-beta1 leading to fibrosis and adhesion to ovarian tissues, and TGF-beta1/Smad signaling pathway is involved in this pathological process.

Advanced Role of Hippo Signaling in Endometrial Fibrosis: Implications for Intrauterine Adhesion.

OBJECTIVE: Intrauterine adhesion (IUA) is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-ß (TGF-ß) signaling pathways to form an intricate network governing the development of fibrosis. DATA SOURCES: Original research articles in English that were published until July 2017 were collected from the PubMed database. STUDY SELECTION: Literature search was conducted using the search terms "endometrial fibrosis OR fibrosis AND or OR intrauterine adhesion OR Asherman syndrome OR IUA," "Hippo AND or OR Hippo/TAZ," "TGF-ß," and "Wnt." Related original research articles were included in the comprehensive analysis. RESULTS: Endometrial fibrosis is recognized as a key pathological event in the development of IUA, which is characterized by epithelial/fibroblast-myofibroblast transition. Myofibroblasts play crucial roles in the pathogenesis of fibrous scarring, and myofibroblast differentiation can be triggered by multiple signaling pathways. Hippo signaling is a critical regulator of the epithelial/fibroblast-myofibroblast transition and α-smooth muscle actin, which exhibits a specific spatiotemporal expression in the endometrium. CONCLUSIONS: Hippo signaling plays a critical role in fibrous diseases and participates in cross talks with Wnt and TGF-ß signaling. Our findings not only contributed to knowledge on the pathogenesis of endometrial fibrosis, but can also serve as a useful resource for developing specific molecular inhibitors for IUA treatment and prevention.

Ovarian Fibrosis: A Phenomenon of Concern.

OBJECTIVE: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. DATA SOURCES: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-ß1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms. STUDY SELECTION: Articles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases. RESULTS: Many cytokines, such as MMPs, TIMPs, TGF-ß1, CTGF, PPAR-γ, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide. CONCLUSIONS: Patients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.

Slow freezing should not be totally substituted by vitrification when applied to day 3 embryo cryopreservation: an analysis of 5613 frozen cycles.

PURPOSE: This study aimed to compare slow freezing (SF) and vitrification (VT) techniques for day 3 embryo cryopreservation in infertile couples. METHODS: This retrospective cohort study enrolled 5613 infertile patients, with 7862 frozen-thawed day 3 embryos and 3845 vitrified-warmed day 3 embryos, from 2010 to 2014, at a single center. The rates of embryo survival, pregnancy, implantation, miscarriage, live birth, and live birth weight were compared between the two groups. RESULTS: A total of 5613 cycles with 5520 transfers were analyzed. Using SF, the rates of overall embryo survival and fully intact blastomeres were lower than those in VT (91.5 vs. 97.4 % and 68.7 vs. 92.3 %, respectively). The rate of good quality embryos after thawing/warming was lower in SF than in VT. In single frozen embryo transfer cycles (FETs), the pregnancy and implantation rates were similar between the two groups (35.0 vs. 40.8 % and 34.6 vs. 35.9 %, respectively). In double FETs, the pregnancy rate per cycle was also similar between the groups (58.8 vs. 58.4 %). The implantation rate per embryo transfer was significantly higher with SF than with VT (38.8 vs. 34.6 %). With adjustment for maternal age and the number of good quality embryos, differences in implantation rate remained significant (adjusted P value, SF vs. VT P < 0.05). No independent effect was found for the method of cryopreservation on the pregnancy rate. No significant differences in the rates of miscarriage, live birth, and live birth weight were observed between the two techniques. CONCLUSIONS: Despite the significantly low embryo survival rate, fully intact blastomere rate, and good quality embryo rate in SF, the pregnancy and implantation rates were not adversely affected in single and double FETs. SF yielded an equivalent miscarriage rate, live birth rate, and live birth weight compared with VT. The SF protocol to cryopreserve day 3 embryos still should be considered.

S100P regulates trophoblast-like cell proliferation via P38 MAPK pathway.

S100P was originally isolated from the placenta, and is expressed in very high levels in trophoblast cells, but its role on trophoblast cells proliferation has not yet been studied. In this study, we aimed to investigate the potential role of S100P in human placental development, and the impact of its expression regulation on cellular function as well as molecular mechanisms involved in trophoblast-like cells. We found that the expression of S100P in first trimester placenta was significantly reduced in spontaneous abortion patients with respect to normal pregnant women. Up-regulation of S100P in JAR cells promoted JAR cells proliferation, and increased the expression of phosphorylated P38 (p-P38) mitogen-activated protein kinase (MAPK) and p-ERK MAPK. However, the effects of S100P on JAR cells proliferation were prevented by P38 inhibitor-SB203580, but not by ERK inhibitor-PD98059. These results showed that S100P may have a physiological role in normal pregnant development, and regulate trophoblast-like cell proliferation via modulating the P38 MAPK pathway.

Intracytoplasmic Sperm Injection Fertilization Rate Does Not Depend on the Proportion of Round-headed Sperm, Small-acrosomal Sperm, or Morphologically Normal Sperm in Patients with Partial Globozoospermia.

BACKGROUND: Generally, intracytoplasmic sperm injection (ICSI) may be the preferable method to treat partial globozoospermia, but whether there exist some correlations between ICSI fertilization rate and the proportion of round-headed sperm or morphologically normal sperm remains open. This study was to explore the correlation between ICSI fertilization rate and the sperm morphology in patients with partial globozoospermia. METHODS: Thirty-four patients diagnosed with partial globozoospermia accepted the following assisted fertilization treatments - 2 cases accepted in-vitro fertilization (IVF) alone, 26 cases accepted ICSI alone, and 6 accepted split IVF/ICSI. Detailed morphological characteristics were described using Diff-Quik rapid staining. Sixty cases accepting IVF or ICSI treatment in our reproductive center were considered as the control group after being matched by relevant criteria. Fertilization rate, embryo quality, embryo implantation rate and clinical pregnancy rate were calculated. RESULTS: Besides very high proportion of round-headed sperm, partial globozoospermia also showed very high proportion of small-acrosomal sperm and very low proportion of morphologically normal sperm. Fertilization rate of IVF (IVF alone plus split IVF) was very low in partial globozoospermia (25.4% ± 17.4%), but ICSI (ICSI alone plus split ICSI) achieved satisfying fertilization rate compared with the control group (66.2% ± 22.5% vs. 68.8% ± 29.4%, P > 0.05). In patients with partial globozoospermia, there were no correlations between ICSI fertilization rate and the proportion of round-headed sperm, small-acrosomal sperm, or morphologically normal sperm. CONCLUSIONS: There was high proportion of small-acrosomal sperm in partial globozoospermia. For patients with partial globozoospermia, ICSI is more preferable than IVF. ICSI fertilization rate does not depend on the proportion of round-headed sperm, small-acrosomal sperm, or morphologically normal sperm.

Randomized, controlled trial comparing the efficacy of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis.

OBJECTIVE: To compare the efficacy of heart-shaped intrauterine balloon and intrauterine contraceptive device (IUD) in the prevention of adhesion reformation after hysteroscopic adhesiolysis. DESIGN: Prospective, randomized, controlled trial. SETTING: University hospital. PATIENT(S): A total of 201 women with Asherman syndrome. INTERVENTION(S): Women were randomized to having either a heart-shaped intrauterine balloon or an IUD fitted after hysteroscopic adhesiolysis. The devices were removed after 7 days. A second-look hysteroscopy was carried out 1 to 2 months after the surgery. MAIN OUTCOME MEASURE(S): Incidence of adhesion reformation and reduction of adhesion score before and after surgery. RESULT(S): Initially 201 cases were recruited; 39 cases dropped out, resulting in 82 cases in the balloon group and 80 cases in IUD group. The age, menstrual characteristics, pregnancy history, and American Fertility Society score before surgery were comparable between the two groups. The median adhesion score reduction (balloon group, 7; IUD group, 7) and the adhesion reformation rate (balloon group, 30%; IUD group, 35%) were not significantly different between the two groups. CONCLUSION(S): The heart-shaped intrauterine balloon and IUD are of similar efficacy in the prevention of adhesion reformation after hysteroscopic adhesiolysis for Asherman syndrome. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN 69690272.

Expression and Distribution of Calcium-Binding Protein S100P in Human Placenta during Pregnancy.

BACKGROUND: S100P is a member of the S100 family of calcium-binding proteins, and it participates in pathophysiological events, such as tumor growth and invasion. Based on the striking similarities between trophoblast cells and tumor cells with regard to proliferative and invasive properties, we raised the question of whether and how S100P expresses in trophoblast cells during development. This study aimed to investigate the expression pattern of S100P in the human placenta during pregnancy development. MATERIALS AND METHODS: In this experimental study, we collected 16 first-trimester placental tissues, 10 second-trimester placental tissues, and 12 term placentas. The mRNA expression levels of S100P were detected by reverse-transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR, the protein expression levels were detected by western blot, and the localization of S100P was measured by immunohistochemical staining. The values obtained from PCR and western blot analysis were expressed as the mean ± SD. Levene's test was used to test equal variances, and one-way analysis of variance (ANOVA) was used to evaluate differences between groups. RESULTS: Protein and mRNA expression of S100P could be detected in placenta during pregnancy, with minor higher levels in first-trimester (p>0.05). Immunohistochemical staining revealed that S100P protein was strongly expressed in syncytiotrophoblasts, and moderate expression was detected in villous cytotrophoblasts and cytotrophoblast columns. The S100P protein was localized to both cytoplasm and nuclei in syncytiotrophoblasts, while it only existed in the cytoplasm of cytotrophoblasts. CONCLUSION: S100P was strongly detected in human placenta during pregnancy. The specific expression and distribution of S100P in human placenta throughout gestation suggested that S100P function might vary with its location in the placenta.