Vascularized Toe Proximal Interphalangeal Joint Transfer in Posttraumatic Fingers: Analysis of Prognostic Factors for Suboptimal Outcomes.

Background: Posttraumatic finger osteoarthritis of the proximal interphalangeal joint (PIPJ) is a difficult problem. Over the past decade, we have reported several methods for improving the outcomes of vascularized toe joint transfer (VJT). In this study, we focused on determining poor prognostic factors which lead to a suboptimal outcome. Methods: A consecutive series of patients with posttraumatic osteoarthritis of the PIPJ who received VJT between January 2008 and January 2021 were enrolled in this study. The senior surgeon (Y.-T.L.) performed the surgery in all cases. In this retrospective study, we reexamine the initial trauma-related soft tissue and bony structure injuries of the recipient finger, to assess the baseline tissue quality before VJT. The injuries were classified into five major categories according to their anatomic region. The functional outcome parameters (including range of motion, percentage of use, and extensor lag of the transferred PIPJ) were collected. Univariate and multivariate linear regression analyses were performed using the generalized estimated equation model to identify the correlation between the injury category involved and functional outcome. Results: A total of 59 digits were enrolled. Our results revealed that the fingers with previous vascular injury that received revascularization procedures had relatively suboptimal functional outcomes. These fingers had a significantly lower percentage of use both before (ß = -0.222, P = 0.006) and after (ß = -0.177, P = 0.006) receiving secondary procedures to improve functional outcome. Conclusions: Patients with prior revascularization surgery were associated with a poor functional outcome after VJT.

The live birth rate of vitrified oocyte accumulation for managing diminished ovarian reserve: a retrospective cohort study.

BACKGROUND: Vitrified M-II oocyte accumulation for later simultaneous insemination has been used for managing POR. Our study aimed to determine whether vitrified oocyte accumulation strategy improves live birth rate (LBR) for managing diminished ovarian reserve (DOR). METHODS: A retrospective study included 440 women with DOR fulfilling Poseidon classification groups 3 and 4, defined as the presence of serum anti-Müllerian hormone (AMH) hormone level < 1.2 ng/ml or antral follicle count (AFC) < 5, from January 1, 2014, to December 31, 2019, in a single department. Patients underwent accumulation of vitrified oocytes (DOR-Accu) and embryo transfer (ET) or controlled ovarian stimulation (COS) using fresh oocytes (DOR-fresh) and ET. Primary outcomes were LBR per ET and cumulative LBR (CLBR) per intention to treat (ITT). Secondary outcomes were clinical pregnancy rate (CPR) and miscarriage rate (MR). RESULTS: Two hundred eleven patients underwent simultaneous insemination of vitrified oocyte accumulation and ET in the DOR-Accu group (maternal age: 39.29 ± 4.23 y, AMH: 0.54 ± 0.35 ng/ml), and 229 patients underwent COS and ET in the DOR-fresh group (maternal age: 38.07 ± 3.77 y, AMH: 0.72 ± 0.32 ng/ml). CPR in the DOR-Accu group was similar in the DOR-fresh group (27.5% vs. 31.0%, p = 0.418). However, MR was statistically higher (41.4% vs. 14.1%, p = 0.001), while LBR per ET was statistically lower (15.2% vs. 26.2%, p < 0.001) in the DOR-Accu group. There is no difference in CLBR per ITT between groups (20.4% vs. 27.5%, p = 0.081). The secondary analysis categorized clinical outcomes into four groups regarding patients' age. CPR, LBR per ET, and CLBR did not improve in the DOR-Accu group. In the group of 31 patients, accumulated vitrified metaphase II (M-II) oocytes reached a total number of ≥ 15, and CPR improved among the DOR-Accu group (48.4% vs. 31.0%, p = 0.054); however, higher MR (40.0% vs. 14.1%, p = 0.03) resulted in similar LBR per ET (29.0% vs. 26.2%, p = 0.738). CONCLUSIONS: Vitrified oocyte accumulation for managing DOR did not improve LBR. Higher MR resulted in lower LBR in the DOR-Accu group. Therefore, the vitrified oocyte accumulation strategy for managing DOR is not clinically practical. TRIAL REGISTRATION: The study protocol was retrospectively registered and was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e) on August 26, 2021.

Comparison of clinical outcomes between conventional in vitro fertilization and intracytoplasmic sperm injection in poor responders with only single oocyte retrieved.

OBJECTIVE: To compare the clinical outcomes between conventional insemination (IVF) and intracytoplasmic sperm injection (ICSI) in poor responders with only a single oocyte retrieved. MATERIALS AND METHODS: This is a retrospective case-control study. Couples who were treated with assisted reproductive technology (ART) with a single oocyte retrieved in Mackay Memorial Hospital from 1996 to 2016 were recruited. All data were categorized into three groups, according to their fertilization method and semen quality: group A, conventional insemination with non-male factor (IVF-NMF, n = 115), group B, ICSI with male factor (ICSI-MF, n = 30), and group C, ICSI with non-male factor (ICSI-NMF, n = 49). RESULTS: No statistically significant difference was observed between IVF and ICSI groups in pregnancy outcomes, including the chemical or clinical pregnancy rate, miscarriage rate, and live birth rate. Similar fertilization rates per oocyte obtained were observed in IVF and ICSI patients, but significantly lower per mature oocyte in the ICSI group (IVF: 91.5%, ICSI-MF: 75.0%, ICSI-NMF: 77.8%). Although there is no statistical significance, the lower live birth rate is observed in group C than others (A:11.5%, B:25%, C:5%, p = 0.187). CONCLUSION: In this study, pregnancy outcomes of conventional in vitro fertilization and ICSI in poor responders with only a single oocyte retrieved were similar. However, the fertilization rate of matured oocytes in ICSI groups is significantly lower than that in the IVF group, indicating that ICSI procedures might cause oocyte damage. Therefore, the choice of fertilization method should be based on semen quality. A randomized controlled trial should be performed to confirm our findings.

Correlation between Sperm Micro Ribonucleic Acid-34b and -34c Levels and Clinical Outcomes of Intracytoplasmic Sperm Injection in Men with Male Factor Infertility.

Few studies have examined the correlation between sperm miRNA levels and clinical outcomes of intracytoplasmic sperm injection (ICSI). In this study, we aimed to assess the correlation of sperm miR-34b, miR-34c, miR-122, and miR-429 levels with ICSI outcomes in men with teratozoospermia and asthenozoospermia. TaqMan microRNA quantitative polymerase chain reaction was used to evaluate the relative expression of miRNAs in sperm. The relative miRNA levels quantified using a comparative method found that the four miRNAs were not associated with fertilization rate and early embryo development. However, revels of miR-34b and miR-34c in teratozoospermia sperm of the live birth group were significantly higher than those in the non-live birth group. Receiver operating characteristic curve analysis revealed that the optimal cut-off delta cycle threshold values of miR-34b and miR-34c were 8.630 and 7.883, respectively. Statistical analysis found that the levels of miR-34b and the miR-34c in teratozoospermic and asthenozoospermic sperm above the thresholds were not associated with the fertilization rate and the high-quality embryo rate above 50%; however, they were more likely to exhibit higher implantation, pregnancy, and live birth rates. miR-34b and miR-34c were significantly associated with ICSI clinical outcomes in male factor infertility, especially teratozoospermia. Further validation is required before it becomes a clinically valid reference indicator.

Metaphase II (MII) human oocytes with smooth endoplasmic reticulum clusters do not affect blastocyst euploid rate.

OBJECTIVE: To investigate whether the rate of euploidy and pregnancy outcomes are affected by smooth endoplasmic reticulum clusters (SERc) and other metaphase II human oocyte dysmorphisms. MATERIALS AND METHODS: Retrospective analysis of the morphologies of metaphase II (MII) human oocytes, which had developed into 590 biopsied blastocysts derived from 109 patients that received preimplantation genetic testing for aneuploidies (PGT-A) cycles between March 2013 and December 2017. The euploid rate of blastocysts that originated from morphologically abnormal or normal oocytes were analyzed. The chromosome status of the blastocysts was determined and analyzed by array comparative genomic hybridization (aCGH) or next generation sequencing (NGS) following trophectoderm biopsy. RESULTS: According to the odds ratios obtained for each oocyte morphotype, no statistically significant relationship was found between oocyte dysmorphisms and euploid rate. Specifically, although SERc-positive oocytes had a higher rate of arrest at two pronuclei, or 2 PN (26.7% vs. 19.4%, p > 0.05), the blastocyst formation rate was not affected as compared with SERc-negative oocytes (40.0% vs. 38.6%, p > 0.05). Among nine euploid embryos derived from oocytes with SERc, three single euploid embryo transfers were performed, of which one resulted in blighted ovum, and two resulted in the births of two healthy, singleton term babies. CONCLUSION: The results presented here suggest that oocyte dysmorphisms do not affect the euploidy rate of the blastocyst. The occurrence of SERc in the oocyte does not seem to impair the developing blastocyst nor does it interfere with good embryo formation rate and euploid rate. Thus, the embryos derived from SERc-positive oocytes could still be considered for embryo transfer if there are no other embryos available.

Is there an optimal timing interval between hCG trigger and oocyte vitrification?

OBJECTIVE: Oocyte vitrification has been developed as a promising alternative to slow freezing; however, the clinical outcome is highly operator dependent. From the past study, we know the timing of cryoprotectant exposure and understand that the intervals between the application of liquid nitrogen and thawing solution are crucial factors in the vitrification process. However, the optimal time intervals between hCG trigger and oocyte vitrification and equilibration remain unknown. This study aimed to evaluate the optimal intervals before and during modified vitrification. MATERIALS AND METHODS: This retrospective study included 66 patients undergoing vitrified-thawed oocyte cycles from June 2018 to May 2019. Oocyte in vitro maturation (IVM) is defined as the maturation in vitro of an immature oocyte collected using a standard pick up procedure. Oocytes were grouped into the following intervals: (1) human chorionic gonadotropin (hCG) trigger to oocyte vitrification (<38 h; 38-39 h; >39 h; IVM) (2) oocyte equilibration time (<10 min; 10-12 min; 12-15 min). The vitrification and warming procedures were performed following the steps as shown in the Cryotec method. RESULTS: A total of 390 mature oocytes were vitrified with the Cryotec method. The survival rates were not significantly different among the various intervals after the hCG trigger (97.59%; 95.54%; 100%); however, there was a trend of decreased survival rate in IVM group (66.67%). The oocyte survival rates were not significantly different among the various times of oocyte equilibration (96.77%; 97.33%; 95.42%). CONCLUSIONS: This was the first study to demonstrate no correlation between oocyte survival rate and the time intervals between hCG trigger and oocyte vitrification. Nor did the oocyte survival rate correlate with the various equilibration times during vitrification, as long as the oocyte was mature. In the future, large, prospective, randomized controlled studies will be required to confirm the clinical outcomes.

Prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency, mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter and Prader-Willi syndrome.

OBJECTIVE: We present prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency (NT), mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter, and Prader-Willi syndrome (PWS). CASE REPORT: A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased NT thickness of 5.6 mm and abnormal maternal serum screening results in the first trimester. The pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15 [16]/45,XX,-15,der(17)t(15;17)(q14;p13)[3]/45,XX,der(15)t(15;15)(q35;q14),-15[2]. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 15q11.2q14 (22,765,628-38,651,755) × 1.0 [GRCh37 (hg19)] with a 15.886-Mb 15q11.2-q14 deletion encompassing TUBGCP5, CYFIP1, NIPA2, NIPA1, SNRPN, SNURF, SNORD116-1, IPW, UBE3A, ACTC1 and MEIS2. The pregnancy was subsequently terminated, and a malformed fetus with facial dysmorphism was delivered. The cord blood had a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15[46]/45,XX,der(3)t(3;15) (q29;q14),-15[2]/45,XX,-15,der(17)t(15;17)(q14;p13)[2]. The placenta had a karyotype of 45,XX,der(5) t(5;15)(q35;q14),-15. Polymorphic DNA marker analysis confirmed a paternal origin of the proximal 15q deletion. CONCLUSION: Increased NT and abnormal maternal serum screening results may prenatally be associated with PWS. Chromosome 15 rearrangements in PWS include mosaicism for de novo multiple unbalanced translocations.

A mouse seminal vesicle-secreted lysozyme c-like protein modulates sperm capacitation.

Lysozyme (LYZ) c-like proteins are primarily present in the testis and epididymis of male reproductive tissues. Here, we report a novel member of the c-type LYZ family, the seminal vesicle-secreted LYZ c-like protein (SVLLP). Three forms of SVLLP were purified from mouse seminal vesicle secretions and characterized as glycoproteins with the same protein core but different N-linked glycans. SVLLP is structurally similar to c-type LYZ proteins. Only one of the 20 invariant residues was altered in the consensus sequence of c-type LYZs; however, the changed residue (N53S) is one of two essential catalytic residues. LYZ activity assays demonstrated that the three glycoforms of SVLLP lacked enzyme activity. SVLLP is primarily expressed in seminal vesicles. Immunohistochemistry revealed that it occurs in the luminal fluid and mucosal epithelium of the seminal vesicles. Testosterone is not the primary regulator for its expression in the seminal vesicle. SVLLP binds to sperm and suppresses bovine serum albumin-induced sperm capacitation, inhibits the acrosome reaction, and blocks sperm-oocyte interactions in vitro, suggesting that SVLLP is a sperm capacitation inhibitor.

Intrauterine adhesion prevention with Malecot catheter after hysteroscopic myomectomy: A novel approach.

OBJECTIVE: Intrauterine adhesion after hysteroscopic myomectomy contributes to infertility, recurrent miscarriages, menstrual irregularities, and hinders pregnancy outcomes. The aim of this study was to apply the indwelling Malecot catheter in prevention of intrauterine adhesion after hysteroscopic myomectomy and to further evaluate the effectiveness of this approach with reported live birth rates in infertile patients who underwent subsequent infertility treatment. MATERIALS AND METHODS: Seventeen patients with FIGO Classification System PALM-COIEN Type 0 or 1 submucous myoma that received hysteroscopic myomectomy were recruited in this retrospective analysis. Post-operative insertion of the Malecot catheter via the aid of the uterine sound was performed and the catheter was left in place for seven days. RESULTS: The mean duration of TTP (time to pregnancy) was 15.6 months after hysteroscopy. Within three years after the operation, 10 out of 17 infertility patients achieved ongoing pregnancy over 12 weeks. Ongoing pregnancy rate was 58.8% (10/17). Eight patients achieved live birth (seven singletons, one twin pregnancy) with mean gestational age of 38 weeks. Live birth rate was 47.1% (8/17). CONCLUSION: The Malecot catheter is an inexpensive, easy-to-operate, and effective physical barrier method for preventing IUA in infertile patients undergoing hysteroscopic myomectomy with high live birth rate and no obvious visible post-operative adhesions.

Dietary Supplementation with Hazelnut Oil Reduces Serum Hyperlipidemia and Ameliorates the Progression of Nonalcoholic Fatty Liver Disease in Hamsters Fed a High-Cholesterol Diet.

Objective: Hazelnut oil (HO) is rich in monounsaturated fatty acids and polyunsaturated fatty acids. This study intended to analyze the effects of hazelnut oil supplementation on the serum lipid profile and nonalcoholic fatty liver disease in hamsters fed a high-cholesterol (HC) diet. Methods: Hamsters were fed a basic diet (control group) and an HC diet (HC group) for 16 weeks (n = 10 in each group). Hamsters were fed an HC diet for four weeks to induce hyperlipidemia and were then fed an HC diet enriched with 5% (low-dose HC + HO group; n = 10) and 10% HO (high-dose HC + HO group; n = 10) for 12 weeks. Serum lipid levels, hepatic changes (including steatosis, inflammation, and fibrosis), and hepatic prooxidant-antioxidant status (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST)) were evaluated after the treatment period. Results: Hamsters in the control group showed normal serum lipid profiles, normal liver function, and moderate glycogen storage without hepatic steatosis. Hamsters in the HC group showed severe hyperlipidemia, severe hepatic steatosis, and moderate steatohepatitis (mononuclear cell and neutrophil infiltration, oval cell hyperplasia, and fibrosis). Compared to the HC group, both the low-dose and the high-dose HC + HO groups showed a significant reduction of hyperlipidemia (serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C levels)) and improved liver function (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)). Additionally, compared to the HC group, intrahepatic triglyceride accumulation (IHTC) was significantly higher in the HC + HO group, while the incidence of steatohepatitis was significantly lower. The intake of the HC diet was associated with a higher level of lipid peroxidation (malondialdehyde, MDA) and a lower concentration of hepatic antioxidant enzymes (SOD, GPx, and GST), and all these factors were partially improved in the low-dose and high-dose HC + HO groups. Conclusions: Our findings indicate that the intake of HO reduced serum hyperlipidemia and oxidative stress and ameliorated the progression of nonalcoholic fatty liver disease in hamsters fed a high-cholesterol diet.

Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR) remains one of the greatest obstacles affecting the chance of a successful live birth after fertility treatment. The present study was set to investigate whether using a "dual trigger" consisted of human chorionic gonadotropin (hCG) plus gonadotropin releasing hormone agonist (GnRH-a) for final oocyte maturation could improve the IVF cycle outcomes for patients with diminished ovarian reserve. METHODS: A total of 427 completed GnRH-antagonist downregulated IVF cycles with fresh embryo transfer (ET) were included in this retrospective analysis. DOR was defined as antral follicle count ≤5 and serum anti-Müllerian hormone level ≤ 1.1 ng/mL. The control group (n = 130) used a 6500 IU of recombinant hCG for trigger, and the study group (n = 297) used 0.2 mg of triptorelin plus 6500 IU of recombinant hCG for trigger. RESULTS: The dual-trigger group had significantly higher oocyte fertilization rate (73.1% vs. 58.6%), clinical pregnancy rate (33.0% vs. 20.7%) and live birth rate (26.9% vs. 14.5%) when compared to the hCG trigger group. In addition, the abortion rate (17.4% vs. 37.0%) and embryo transfer cancellation rate (6.1% vs. 15.4%) were both significantly lower in the dual trigger group. The primary outcome measure was the live birth rate per oocyte retrieval cycle. Secondary outcome measures were embryo transfer cancellation rate, clinical pregnancy rate, implantation rate, chemical pregnancy rate and abortion rate per oocyte retrieval cycle. CONCLUSIONS: Dual triggering the final oocyte maturation with GnRH-a and standard dose of hCG can significantly improve the live birth rate, clinical pregnancy rate, and fertilization rate in women with diminished ovarian reserve undergoing GnRH antagonist down-regulated IVF-ICSI cycles.

Early blastulation of day 4 embryo correlates with the increased euploid rate of preimplantation genetic screening cycles.

OBJECTIVE: It is known that embryos with faster growing potential, especially in blastocyst development, correlate with the increased euploid rate. Our study investigated the preimplantation genetic screening cycle to analyze the correlation between early blastulation (EB) on day 4 embryo and the euploid rate. MATERIALS AND METHODS: This is a retrospective study examining 273 biopsied blastocysts after preimplantation genetic screening obtained from 54 patients from March 2013 to March 2017. Of the 273 biopsied embryos, 81 had early blastulation on day 4 and were classified as the EB (+) group, while the other 192 had no early blastulation and were classified as the EB (-) group. Euploid rates were compared between the two groups. A total of 34 single euploid embryos were transferred, with 14 from the EB (+) group and 20 from the EB (-) group. Clinical pregnancy was compared between the groups. RESULTS: There is a statistically significant increase in the euploid rate in the EB (+) group (49.4% vs. 34.4%, p = 0.02). The clinical pregnancy rate was also increased in the single euploid embryo transfer group with early blastulation, but did not reach statistical significance (71.4% vs. 50.0%, p = 0.211). CONCLUSIONS: Early blastulation of day 4 embryo correlates significantly with the euploid rate. Early blastulation of day 4 embryo may serve as a potential aid for embryo selection for transfer in preimplantation genetic screening cycles.

Digynic triploidy in a fetus presenting with semilobar holoprosencephaly.

OBJECTIVE: We present digynic triploidy in a fetus with semilobar holoprosencephaly (HPE). CASE REPORT: A 32-year-old, gravid 1, para 0, woman underwent prenatal ultrasound examination at 12 weeks of gestation, and the ultrasound showed relative macrocephaly, a small non-cystic placenta, and a fetus with absent nasal bone and semilobar HPE. The pregnancy was terminated subsequently, and a 50-g fetus was delivered with a relatively enlarged head and premaxillary agenesis. The placenta was small and non-cystic. Postnatal cytogenetic analysis of the umbilical cord revealed a karyotype of 69, XXX. Postnatal DNA marker analysis using quantitative fluorescent polymerase chain reaction assays and the polymorphic short tandem repeat markers for chromosome 18 and 20 on the placental tissues showed a diallelic pattern with a dosage of 1:2 (paternal allele to maternal allele ratio), indicating a maternal origin of the triploidy. CONCLUSION: Fetuses with digynic triploidy may present relative macrocephaly, semilobar HPE and a small placenta on prenatal ultrasound.

Early blastulation (EB) of day 4 embryo is predictive of outcomes in single embryo transfer (SET) cycles.

OBJECTIVE: The aim of this study was to assess whether the early blastulation (EB) of day 4 embryo is a useful predictor for outcomes in fresh elective single embryo transfer (eSET) cycles. MATERIALS AND METHODS: We retrospectively enrolled patients undergoing fresh SET cycles in our hospital from April 2014 to September 2016 and met with the following criteria: 1) age <38 years, 2) first IVF/ICSI cycle, 3) at least two blastocysts with morphological grading better than or equal to 4BB. RESULTS: A total of 81 patients were included. Of whom, 55 patients (68%) had undergone eSET with embryos that had early blastulation on day 4 while the other 26 patients had had no EB. Early blastulation has shown a higher rate of good blastocyst (84.3% vs. 60.5%, p < 0.0001). The clinical pregnancy rate of EB group was significantly higher than that of non-EB group (56.4% vs. 27.0%, p = 0.013). There is also a tendency in EB group to have a lower abortion rate (3.23% vs. 28.6%, p = 0.081). CONCLUSIONS: EB on day 4 is a useful predictor of the quality of the following embryos (i.e. day 5 embryo). It is a simple tool in selecting the best embryo to get a higher pregnancy rate in fresh eSET cycles. TRIAL REGISTRATION: This study was supplementally registered by the MacKay Memorial Hospital Institutional Review Board on April 18, 2017 (registration No. 17MMHIS039e).

Serine Protease Inhibitor SERPINE2 Reversibly Modulates Murine Sperm Capacitation.

SERPINE2 (serpin peptidase inhibitor, clade E, member 2), predominantly expressed in the seminal vesicle, can inhibit murine sperm capacitation, suggesting its role as a sperm decapacitation factor (DF). A characteristic of DF is its ability to reverse the capacitation process. Here, we investigated whether SERPINE2 can reversibly modulate sperm capacitation. Immunocytochemical staining revealed that SERPINE2 was bound onto both capacitated and uncapacitated sperm. It reversed the increase in BSA-induced sperm protein tyrosine phosphorylation levels. The effective dose and incubation time were found to be >0.1 mg/mL and >60 min, respectively. Calcium ion levels in the capacitated sperm were reduced to a level similar to that in uncapacitated sperm after 90 min of incubation with SERPINE2. In addition, the acrosome reaction of capacitated sperm was inhibited after 90 min of incubation with SERPINE2. Oviductal sperm was readily induced to undergo the acrosome reaction using the A23187 ionophore; however, the acrosome reaction was significantly reduced after incubation with SERPINE2 for 60 and 120 min. These findings suggested that SERPINE2 prevented as well as reversed sperm capacitation in vitro. It also prevented the acrosome reaction in in vivo-capacitated sperm isolated from the oviduct. Thus, SERPINE2 could reversibly modulate murine sperm capacitation.

Day 4 good morula embryo transfer provided compatible live birth rate with day 5 blastocyst embryo in fresh IVF/ET cycles.

OBJECTIVE: Embryo transfers during cleavage stage (day 2 or day 3) and blastocyst stages (day 5 or day 6) are common in current daily practice in fresh IVF/ET cycles. Data regarding transferring day 4 embryos, morula/compact stage, is still restricted and the grading system is also inconsistent, as between IVF clinics. This study provided a new detailed classification system for morula/compact stage embryos and compared successes rates between day 4 and day 5 ET. MATERIALS AND METHODS: This was a retrospective study. A review of medical records from January 1st, 2013, to December 31st 2015, performed for all conventional insemination and ICSI cycles with a GnRH-antagonist protocol at the Infertility Division of MacKay Memorial Hospital in Taipei City, Taiwan. RESULTS: There were 427 cycles included in our study, 107 in study group (day 4 MET) and 320 in control group (day 5 BET). Pregnancy rates and live birth rate were compatible, as between morula embryo transfer (MET) and blastocyst embryo transfer (BET). The implantation rate (36.3% vs. 39.6%, respectively, p = 0.500), clinical pregnancy rate (49.5% vs. 51.9%, respectively, p = 0.737), and live birth rate (42.1% vs. 45.6%, respectively, p = 0.574) were statistically insignificant between groups. The term birth rate was statistically higher in the MET group than in the BET group (95.7% vs. 79.5%, respectively, p = 0.006). When the clinical outcomes between day 4 good MET and day 5 good BET were compared, the results were compatible. The implantation rate (48.8% vs. 41.1%, respectively, p = 0.335), clinical pregnancy rate (55.0% vs. 53.2%, respectively, p = 0.867), and live birth rate (47.5% vs. 47.1%, respectively, p = 1.000) showed no significant difference. The term birth rate was also higher in day 4 good MET group than in day 5 good BET group (100% vs. 78.3%, respectively, p = 0.025). CONCLUSION: In this study, we performed day 4 MET avoid BET on Sunday. The grading system we provided was more detailed for embryo selection and it was easier to remember. Our data showed that morula embryo transfer might be a flexible, easier and applicable method for embryo transfer in daily routine.

Expression of cystatin C in the female reproductive tract and its effect on human sperm capacitation.

BACKGROUND: Cystatin C (CST3), a cysteine protease inhibitor in seminal plasma, is expressed in animal uteri. However, its expression in the human female reproductive tract and its effect on human sperm capacitation are unclear. METHODS: The cellular localization of CST3 was observed using immunohistochemistry. The binding of CST3 to sperm was examined using immunocytochemistry. Sperm motility parameters were analyzed using computer-assisted sperm analysis. Sperm capacitation was evaluated by analyzing cholesterol content, protein tyrosine phosphorylation levels, and the acrosome reaction. RESULTS: Immunohistochemical staining demonstrated that CST3 is prominently expressed in the female reproductive tract, including the epithelial lining and cervix and endometrium fluids, particularly at times near ovulation. It can bind to human sperm on the post-acrosomal head region and the mid and principal piece of the tail. CST3 enhances sperm motility and inhibits the signal initiating sperm capacitation, i.e., efflux of cholesterol from the sperm plasma membrane and a late sperm capacitation event, i.e., the increase in the sperm protein tyrosine phosphorylation. The suppressive trend on sperm acrosome reaction further supports CST3's ability to inhibit sperm capacitation. CONCLUSIONS: These findings suggest that cervical CST3 may prevent precocious capacitation and acrosome reaction, thus preserving sperm fertilizing ability before it reaches the fallopian tube. Additionally, CST3 may help sperm enter the upper reproductive tract by enhancing sperm motility.

Application of non-invasive prenatal testing in late gestation in a pregnancy associated with intrauterine growth restriction and trisomy 22 confined placental mosaicism.

OBJECTIVE: We present the application of non-invasive prenatal testing (NIPT) in late gestation in a pregnancy associated with intrauterine growth restriction (IUGR) and trisomy 22 confined placental mosaicism (CPM). CASE REPORT: A 35-year-old pregnant woman underwent chorionic villus sampling (CVS) at 12 weeks of gestation. The pregnancy was conceived by in vitro fertilization and intracytoplasmic sperm injection. CVS revealed a karyotype of 47,XY,+22 in all of 15 cultured chorionic villi cells. Array comparative genomic hybridization analysis on uncultured chorionic villi revealed a result consistent with trisomy 22. The woman underwent amniocentesis at 17 weeks of gestation. Amniocentesis revealed a karyotype of 46,XY in all 20 colonies of cultured amniocytes. Additional polymorphic DNA marker analysis excluded uniparental disomy 22. The parental karyotypes were normal. Prenatal ultrasound at 23 weeks of gestation revealed fetal retrognathia, IUGR and a calcified placenta. NIPT at 27 weeks of gestation using maternal plasma cell-free DNA analysis showed a chromosome Z-score of 5.74 for chromosome 22 (the Z-score for each pair of chromosomes is defined as "increased" if >3), indicating an abnormal placenta with trisomy 22 CPM leading to IUGR in the fetus. At 36 weeks of gestation, a 1754-g male fetus was delivered with cleft palate and imperforate anus but no other phenotypic abnormalities. The cord blood had a karyotype of 46,XY (40/40 cells), the umbilical cord had a karyotype of 47,XY,+22[9]/46,XY[31], and the placental tissues had a karyotype of 47,XY,+22[15]/46,XY[25]. CONCLUSION: NIPT in late gestation is useful in detection of placental abnormality associated with CPM and IUGR but a normal karyotype at amniocentesis.

Outcomes of anti-Müllerian hormone-tailored ovarian stimulation protocols in in vitro fertilization/intracytoplasmic sperm injection cycles in women of advanced age.

OBJECTIVE: We aimed to compare the outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in women of advanced age (>40 years) using anti-Müllerian hormone (AMH)-tailored ovarian stimulation protocols versus conventional protocols based on antral follicle count (AFC). MATERIALS AND METHODS: We retrospectively reviewed 210 women who underwent IVF/ICSI cycles: 116 women underwent stimulation protocols that were tailored to their AMH levels, whereas 94 women received treatment using conventional stimulation protocols based on AFC as the ovarian reserve marker. RESULTS: The following parameters were significantly higher in the AMH-tailored group than in the conventional group: initial and total doses (IU) of recombinant follicle-stimulating hormone (rFSH) used for stimulation (514.2 ± 137.9 vs. 452.3 ± 135.3, p = 0.001; 4713.8 ± 1618.8 vs. 4047.2 ± 1366.0, p = 0.007, respectively), ovum pick-up rate (OPU; 88.8% vs. 75.5%, p = 0.016), serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) administration (1818.5 ± 1422.4 vs. 1394.0 ± 929.0 pg/mL, p = 0.028), number of oocytes retrieved (7.4 ± 5.1 vs. 5.5 ± 3.4, p = 0.007), number of embryos per case (4.2 ± 3.2 vs. 3.3 ± 2.5, p = 0.048), clinical pregnancy rates (22.4% vs. 8.5%, p = 0.008), implantation rates (13.1% vs. 3.9%, p = 0.001), and live birth rates per cycle (15.5% vs. 6.4%, p = 0.049). CONCLUSION: Individualized controlled ovarian stimulation (COS) protocols tailored to patients' AMH levels may improve the pregnancy rate, implantation rate, and live birth rate in women of advanced age undergoing IVF/ICSI compared with those receiving conventional stimulation protocols.

Prenatal diagnosis and array comparative genomic hybridization characterization of interstitial deletions of 8q23.3-q24.11 and 8q24.13 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and haploinsufficiency of TRPS1, RAD21 and EXT1.

OBJECTIVE: The aim of this research was to present prenatal diagnosis of Langer-Giedion syndrome (LGS/TRPS type II) and Cornelia de Lange syndrome-4 (CDLS4). MATERIALS AND METHODS: A 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis of amniocentesis revealed an interstitial deletion of chromosome 8q or del(8)(q23.3q24.13). Level II prenatal ultrasound examination revealed craniofacial dysmorphism. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial dysmorphism of LGS/TRPS type II and CDLS4. Whole-genome array comparative genomic hybridization (aCGH) on the DNA extracted from cultured amniocytes was performed. RESULTS: The analysis by aCGH revealed a result of arr 8q23.3q24.11 (116,087,006-118,969,399)×1, 8q24.13 (123,086,851-124,470,847)×1 (NCBI build 37) with a 2.88-Mb deletion of 8q23.3-q24.11 encompassing six OMIM genes, TRPS1, EIF3H, RAD21, SLC30A8, MED30, and EXT1, and a 1.383-Mb deletion of 8q24.13 encompassing four OMIM genes, ZHX2, DERL1, ZHX1, and ATAD2. CONCLUSION: In the present case, the conventional cytogenetic analysis of cultured amniocytes revealed del(8)(q23.3q24.13), whereas aCGH analysis of cultured amniocytes showed the deletions of 8q23.3-q24.11 and 8q24.13 with the presence of the segment 8q24.12. Therefore, aCGH provides the advantage of better understanding of the nature of interstitial deletion and genotype-phenotype correlation in this case.