Pregnancy Rates after Hysteroscopic Endometrial Polypectomy versus Endometrial Curettage Polypectomy: A Retrospective Study.

Background and Objectives: A relationship between endometrial polypectomy and in vitro fertilization (IVF) pregnancy outcomes has been reported; however, only a few studies have compared polyp removal techniques and pregnancy rates. We investigated whether different polypectomy techniques with endometrial curettage and hysteroscopic polypectomy for endometrial polyps affect subsequent pregnancy outcomes. Materials and Methods: Data from 434 patients who had undergone polypectomy for suspected endometrial polyps using transvaginal ultrasonography before embryo transfer in IVF at four institutions between January 2017 and December 2020 were retrospectively analyzed. Overall, there were 157 and 277 patients in the hysteroscopic (mean age: 35.0 years) and curettage (mean age: 37.3 years) groups, respectively. Single-blastocyst transfer cases were selected from both groups and age-matched to unify background factors. Results: In the single-blastocyst transfer cases, 148 (mean age: 35.0 years) and 196 (mean age: 35.9 years) were in the hysteroscopic and curettage groups, respectively, with the 148 cases matched by age. In these cases, the pregnancy rates for the first embryo transfer were 68.2% (odds ratio (OR): 2.14) and 51.4% (OR: 1.06) in the hysteroscopic and curettage groups, respectively; the resulting OR was 2.03. The pregnancy rates after up to the second transfer were 80.4% (OR: 4.10) and 68.2% (OR: 2.14) in the hysteroscopic and curettage groups, respectively, in which the OR was 1.91. The live birth rates were 66.2% (OR: 1.956) and 53.4% (OR: 1.15) in the hysteroscopic and curettage groups, respectively, in which the odds ratio was 1.71. These results show the effectiveness of hysteroscopic endometrial polypectomy compared to polypectomy with endometrial curettage. No significant difference was found regarding the miscarriage rates between the two groups. Conclusions: Hysteroscopic endometrial polypectomy resulted in a higher pregnancy rate in subsequent embryo transfer than polypectomy with endometrial curettage. Therefore, establishing a facility where polypectomy can be performed hysteroscopically is crucial.

Usefulness of expanding the indications of early rescue intracytoplasmic sperm injection.

Purpose: Early rescue intracytoplasmic sperm injection (ICSI) is often performed in cases in which not even a single oocyte has extruded a second polar body 6 h after insemination. We evaluated the usefulness of expanding the indications of early rescue ICSI to cases in which <80% of oocytes have extruded second polar bodies 6 h after insemination. Methods: Early rescue ICSI was performed on oocytes that were denuded 2.5 h post-insemination and whose extrusion of the second polar bodies had been examined 6 h post-insemination with a PolScope. Results: In vitro fertilization was performed on 24 496 oocytes of 4944 cycles, and 1438 cycles had <80% rate of the second polar body extrusion. Rescue ICSI was performed on 3933 oocytes. Three pronuclei (3PN) incidence of rescue ICSI was 3.0% in oocytes with ≥50% rate of the second polar body extrusion. With respect to the second polar body extrusion rate, no differences were observed in normal fertilization, blastocyst development, implantation, miscarriage, or live birth rates for rescue ICSI. Conclusion: By expanding the indications of early rescue ICSI using the PolScope to cases in which <80% of oocytes have extruded the second polar bodies, many fertilized oocytes can be obtained without considerably increasing the 3PN rate.

[A Case of Stage â £ Pancreatic Head Cancer with Aortic Lymph Node Metastasis Treated with 40 Courses of mFOLFIRINOX Therapy after Surgery and Maintaining PR].

The patient was a male in his 60s who presented with obstructive jaundice and was diagnosed with pancreatic head cancer. He was referred to the Department of Surgery 2 months later due to prolonged jaundice and immediately underwent pylorus-preserving pancreatoduodenectomy with the diagnosis of resectable pancreatic cancer. Pathology showed pN1b (14/37), but 16b1 interaorticocaval was 0/1. The patient was then diagnosed with Stage ⅡB, R0. After completion of adjuvant chemotherapy with S-1, 1 year after surgery, CA19-9 was reelevated and PET/CT-positive enlarged lateroaortic lymph nodes and multiple nodules in both lungs were observed. The lymph nodes were also seen on preoperative CT, and the preoperative diagnosis was Stage Ⅳ. After insertion of an implantable central venous port, mFOLFIRINOX therapy was initiated. The patient had an anaphylactic reaction after 7 courses of L-OHP, and the treatment was continued without L-OHP. After 40 courses of mFOLFIRINOX therapy, the aortic lymph nodes reduced in size, PET results were negative, and the pulmonary nodules partially resolved. We report a case of a patient with Stage Ⅳ pancreatic head cancer who maintained PR for more than 1 year and 7 months after the initiation of mFOLFIRINOX therapy and survived for more than 2 years and 10 months since the initial diagnosis.

Early rescue oocyte activation for activation-impaired oocytes with no second polar body extrusion after intracytoplasmic sperm injection.

PURPOSE: When rescue artificial oocyte activation (ROA) is performed on the day after intracytoplasmic sperm injection (ICSI) or later, embryonic development is poor and seldom results in live births. The efficacy of an early ROA after ICSI is unclear. Is early ROA effective in rescuing unfertilized oocytes that have not undergone second polar body extrusion several hours after ICSI? METHODS: We performed retrospective cohort study between October 2016 and September 2019, targeting 2891 oocytes in 843 cycles when ICSI was performed. We performed ROA with calcium ionophore on 395 of the 475 oocytes with no second polar extrusion 2.5-6 h after ICSI. RESULTS: The normal fertilization rate of ROA oocytes was significantly higher than non-ROA oocytes (65.8% vs 6.7%, P < 0.001). The blastocyst development rate in ROA oocytes was significantly lower than spontaneously activated oocytes (48.9% vs 67.2%, P < 0.001). The ROA oocyte implantation rate did not significantly differ from the spontaneously activated oocytes (36.0% vs 41.2%). We observed no differences in the implantation rates and blastocyst development rates over the 2.5-6 h from ICSI until ROA. CONCLUSION: Early ROA is effective, and the optimal timing appears to be 2.5-6 h after ICSI.

Factor XII gene expression in endometrial stromal cells during decidualisation.

Decidualisation of endometrial stromal cells (ESC) is a prerequisite for the implantation of human embryos. Identification of genes that are upregulated or downregulated during decidualisation could lead to a better understanding of the molecular mechanisms involved in this process. In the present study, we examined differences in gene expression between decidualised and non-decidualised cells using microarray analysis and found that Factor XII (FXII) gene expression was upregulated during decidualisation. Furthermore, we also examined the expression of FXII by human ESC before and during pregnancy, as well as its expression by cells that had undergone decidualisation in vitro. Weak expression of FXII mRNA was detected in the non-pregnant endometrium that increased gradually from the proliferative to the secretory endometrium. During pregnancy, FXII mRNA expression was markedly increased in decidualised endometrium. When sex steroids (200 pg mL(-1) of 17beta-oestradiol and 100 ng mL(-1) of progesterone) were used to induce in vitro decidualisation of ESC, the expression of FXII mRNA increased by approximately 25.3-fold compared with that in non-decidualised ESC. Using western blotting, we confirmed the presence of FXII protein (80 kDa) in ESC after in vitro decidualisation. Increased expression of FXII in ESC during decidualisation suggests that the kallikrein-kininogen-kinin system may be activated during the implantation of human embryos.

Ghrelin is involved in the decidualization of human endometrial stromal cells.

Successful implantation involves a complex interaction between the endometrium and the embryo. It is well known that several neuropeptides are expressed in the endometrium and placenta during embryonal implantation, suggesting an important role as chemical mediators of the feto-maternal relationship. Ghrelin has recently been identified as the endogenous ligand for the GH secretagogue receptor. Ghrelin is a peptide hormone with many physiological functions, and its expression in the human placenta has been reported. To investigate the involvement of ghrelin in embryonal implantation, we assessed the spatio-temporal expression pattern of ghrelin and its receptor in the human endometrium and placenta through the normal menstrual cycle and in early pregnancy. We also examined the effect of ghrelin on the decidualization of endometrial stromal cells (ESC). Weak expression of ghrelin mRNA was detected in the nonpregnant endometrium, and it was dramatically increased in the decidualized endometrium. A GH secretagogue receptor mRNA was detected in the endometrium throughout the normal menstrual cycle and in early pregnancy, but not in the first trimester placenta. Immunohistochemical analysis using an antighrelin antibody revealed strong signals in decidual cells and extravillous trophoblast cells. Coculture with first trimester placenta up-regulated ghrelin mRNA expression by primary cultured ESC, although sex steroids and 8-bromo-cAMP had no effect. In addition, ghrelin enhanced the decidualization of ESC induced by 8-bromo-cAMP (8-Br-cAMP) in vitro. Thus, ghrelin is a novel paracrine/autocrine factor that is involved in cross-talk between the endometrium and embryo during embryonal implantation.

Expression of neuropeptide Y is increased in murine endometrial epithelium during the peri-implantation period under regulation by sex steroids.

Oligopeptide hormones are involved in cell-cell interaction during embryonal implantation and neuropeptide Y (NPY) is expressed in the human placenta and decidual cells in the third trimester of pregnancy. However, there is no report regarding the intrauterine localisation and the functions of NPY during the peri-implantation period. In the present study, the spatiotemporal changes in NPY expression in the murine uterus during the peri-implantation period were investigated using reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and immunohistochemical techniques, as were the effects of sex steroids on NPY mRNA expression in primary cultured murine uterine epithelial cells. Neuropeptide Y mRNA was increased in the pregnant murine uterus, as well as in the pseudopregnant murine uterus, during the peri-implantation period. Immunohistochemical analysis revealed increases in NPY expression in luminal and glandular epithelial cells and decidualised stromal cells. Neuropeptide Y mRNA expression was strongly induced in cultured epithelial cells in response to sex steroids. The data suggest that NPY is involved in cell-cell interactions during embryonic implantation.

Polycystic ovary syndrome treated with laparoscopic ovarian drilling with a harmonic scalpel. A prospective, randomized study.

OBJECTIVE: To evaluate the endocrinologic profile and reproductive outcome after laparoscopic drilling using a harmonic scalpel for polycystic ovarian syndrome (PCOS) in clomiphene-resistant infertile women. STUDY DESIGN: We performed a prospective, randomized study of 34 infertile women with PCOS. Group A (17 women) underwent laparoscopic ovarian drilling using a harmonic scalpel laser. Group B (control group, 17 women) underwent laparoscopic ovarian drilling using a neodymium-yttrium-aluminum-garnet laser. Change in the hormonal profile after surgery, ovulation rate and pregnancy rate were compared between groups A and B. RESULTS: LH and testosterone serum levels and the LH-FSH ratio showed a statistically significant reduction after surgery, and the spontaneous ovulation rate was 94% in both groups. The cumulative pregnancy rates within two years of follow-up were 77% in group A and 60% in group B. CONCLUSION: Laparoscopic ovarian drilling using a harmonic scalpel is an effective treatment for PCOS in clomiphene-resistant, anovulatory women: it results in ovulation and conception without major complications.

Validity of trans-rectal ultrasound-guided embryo transfer against retroflexed uterus.

Background: Embryo transfer is one of the most critical steps affecting the success of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer. It has been reported that uterine contraction caused by touching the uterine fundus at the time of embryo transfer decreased the pregnancy rate. It was demonstrated that there is a significant rise in the pregnancy rate by adequate positioning of embryos. Transabdominal ultrasound-guided embryo transfer has been reported to improve the pregnancy rate compared with the clinical touch method. The improvement of the pregnancy rate under ultrasound guidance can be attributed to the accurate positioning of the embryos aided by good visualization without touching the uterine fundus. However, sometimes difficulties are encountered when visualizing the tip of the catheter in cases where the patient has a retroflexed uterus. Methods: In the present study, we investigated the difference in the pregnancy rates and in the implantation rates between transabdominal ultrasound-guided group and trans-rectal ultrasound-guided group in retroflexed cases. Results and Conclusion: We found that the pregnancy rate and the implantation rate were higher among the trans-rectal group compared with the transabdominal group in retroflexed cases. The difference between the two groups was statistically significant. (Reprod Med Biol 2003; 2: 159-163).

Analysis on the promoter region of human decidual prolactin gene in the progesterone-induced decidualization and cAMP-induced decidualization of human endometrial stromal cells.

PURPOSE: To elucidate the promoter region of human decidual prolactin (dPRL) gene in the human endometrial stromal cells (ESC). METHODS: Various segments of the human dPRL promoter that direct the expression of the secreted alkaline phosphatase (SEAP) reporter gene were transfected into human ESC decidualized by estrogen (E) + progesterone (P) or cyclic AMP (cAMP) to identify E + P or cAMP responsive elements. RESULTS: The region between nucleotides -2038 and -1605 relative to the transcriptional initiation site includes two activator protein-1 (AP-1) sites, which both provided maximal response to E + P or cAMP in decidualized cells. When either AP-1 site was mutated, response in the promoter activity to both E + P or cAMP response showed a decrease compared with control. The region between -310 and -285 that contains consensus-binding sequences for transcription factors of CCAAT/Enhancer-binding proteins (C/EBP) contributed to E + P and cAMP response in decidualized cells. Also, the 5'-flanking region that extends 79 base pairs upstream, including an imperfect cAMP response element (CRE), contributed to E + P and cAMP response. In cells treated with E + P or cAMP for 10 days, mutant of C/EBP-binding site showed an increase in promoter activity comparing to dPRL-2038. In contrast, treatment with PKI showed a decrease in promoter activity in cells treated with E + P or cAMP alone. CONCLUSIONS: These results suggest that cAMP-induced region of the human dPRL promoter resides between -1862 and -1856, -1703 and -1697, -310 and -285, and that the sequences between -1862 and -1856, -1703 and -1697 of the promoter display E + P-induced promoter activity. Furthermore, the current study indicates that E + P or cAMP cooperatively regulate the dPRL gene transcription through some transcriptional factors such as C/EBP, CREB, and other cofactor(s), and that some repressor(s) or corepressor(s) may be involved in the C/EBP-binding site of the human dPRL promoter.

Expression of matrix metalloproteinase-3 in mouse endometrial stromal cells during early pregnancy: regulation by interleukin-1alpha and tenascin-C.

During the peri-implantation period, the endometrium undergoes tissue remodeling and cellular rearrangement. To clarify the involvement of matrix metalloproteinases (MMPs) in endometrial remodeling, we isolated total RNAs from the endometrium of non-pregnant and pregnant mice on days 3 to 5 and evaluated mRNA expression of MMP-2, -3, -9, -11 and -13 using reverse transcription-polymerase chain reaction (PCR). Prompt increases in MMP-3 and -13 mRNA were found on day 4 of pregnancy. Quantitative real-time PCR showed that expression of MMP-3 and -13 increased significantly on day 4, up to 8.4 +/- 2.7 times and 3.4 +/- 1.5 times, respectively, the level in non-pregnant endometrium (p < 0.05). On day 4, immunohistochemistry demonstrated MMP-3-positive endometrial stromal cells. At the same time, tenascin-C (TN-C) mRNA increased 11.1 +/- 4.0 times from the level in non-pregnant endometrium (p < 0.004). To clarify regulation of MMP-3 expression, we examined the effects of interleukin-1alpha (IL-1alpha) and TN-C on MMP-3 mRNA in cultured mouse endometrial stromal cells. Both substances resulted in a dose-dependent increase in MMP-3 mRNA (6.1 +/- 1.8-fold at 1 ng/ml of IL-1alpha and 3.9 +/- 1.8-fold at 10 mug/ml of TN-C). This study shows that MMP-3 expression is upregulated in endometrial stromal cells of the peri-implantation period and may be controlled by IL-1alpha and TN-C.

The effect of RANTES on human sperm chemotaxis.

BACKGROUND: Follicular fluid (FF) is a powerful stimulator of human sperm hyperactivation and the acrosome reaction. FF causes sperm accumulation by way of chemotaxis. The chemoattractant in FF has not yet been identified in the human. It is well known that some types of chemokine such as RANTES (Regulated on Activation Normal T Expressed and Secreted Chemokine) exist in genital tract fluids (for example, FF, seminal plasma and uterine fluid). Few reports appear to exist concerning the direct effect of chemokines on the function of human sperm. METHODS: The chemotactic effect of RANTES on human sperm were investigated by capillary and double-chamber assays, while the chemokinetic effect was investigated using computer-assisted sperm analysis. RESULTS: Both the capillary and double-chamber assays demonstrated a significant chemotactic effect of RANTES on human sperm. Anti-RANTES rabbit IgG partially neutralized the chemotactic effect of FF. In contrast, no statistically significant chemokinetic effect was observed in any motility parameter. CONCLUSIONS: Here, it was demonstrated that mRNA for the RANTES receptors CCR-1 and CCR-5 are present in human sperm. Furthermore, RANTES is involved in the chemotactic effect of FF in vitro.

Specific and transient up-regulation of proprotein convertase 6 at the site of embryo implantation and identification of a unique transcript in mouse uterus during early pregnancy.

The present investigation was conducted to identify and characterize an mRNA that was found by RNA differential display to be uniquely regulated at the sites of embryo implantation in mouse uterus. This mRNA was upregulated at the sites of blastocyst attachment at implantation and was identified as proprotein convertase 6 (PC6). PC6 mRNA level was low in the nonpregnant and early pregnant uterus before embryo implantation commenced (before Day 4.5, vaginal plug = Day 0). During the initiation and progression of blastocyst attachment (around Day 4.5), the mRNA was dramatically upregulated only at the implantation sites. The increased transcription was maintained on Day 5.5; the mRNA level declined slightly on Day 6.5 and then fell sharply to reach the nonpregnant level around Days 8.5-10.5. Thus, the upregulation is transient and coincides with the period of embryo attachment and implantation; it is also very specific to implantation sites. In situ hybridization analysis localized the mRNA expression predominantly in the decidual cells immediately surrounding the implanting embryo at the antimesometrial pole. Additionally, multiple mRNA species resulting from alternative splicing were observed in the uterus, as previously reported in the intestine and brain, and further analysis of these transcripts identified a uterine-specific PC6 mRNA. These data lead us to suggest that PC6 plays an important role in the processes of stromal cell decidualization and embryo implantation.

A novel serine protease of the mammalian HtrA family is up-regulated in mouse uterus coinciding with placentation.

This paper characterizes a novel gene, previously identified as uniquely regulated at implantation in mouse uterus. We cloned its full mRNA sequence encoding a serine protease possessing an IGF-binding domain and named it pregnancy-related serine protease (PRSP). PRSP is structurally similar to mammalian HtrA1 (56% amino acid similarity). Northern analysis revealed that the expression of PRSP mRNA was low before pregnancy, but it was increased at implantation and markedly up-regulated post-implantation. In-situ hybridization localized low levels of mRNA expression to the epithelium and stroma during very early pregnancy, but high expression to the decidual cells on day 8.5, primarily at the mesometrial pole where the placenta was forming. By day 10.5, PRSP mRNA was detected in the placenta. We also cloned an alternatively spliced PRSP mRNA that is expressed at a very low level. We located PRSP gene on chromosome 5 and established its intron/exon structure, which unambiguously explains how the two mRNA variants are produced through alternative splicing. Based on PRSP protein domain structure and its unique expression during pregnancy, we propose that PRSP plays an important role in the formation/function of the placenta.