The impact of serum estradiol and progesterone levels during implantation on obstetrical complications and perinatal outcomes in frozen embryo transfer.

BACKGROUND: This study sought to evaluate obstetric complications and perinatal outcomes in frozen embryo transfer (FET) using either a natural cycle (NC-FET) or a hormone therapy cycle (HT-FET). Furthermore, we investigated how serum levels of estradiol (E2) and progesterone (P4) on the day of and 3 days after embryo transfer (ET) correlated with clinical outcomes in the two groups. METHODS: We conducted a retrospective, single-center study from January 1, 2015, to December 31, 2019. The study included couples who underwent NC-FET or HT-FET resulting in a singleton live birth. Serum levels of E2 and P4 were measured on the day of and 3 days after ET. The primary outcomes assessed were preterm birth rate, low birth weight, macrosomia, hypertensive disorders in pregnancy, gestational diabetes mellitus, postpartum hemorrhage, and placenta-related complications. RESULTS: A total of 229 singletons were included, with 49 in the NC-FET group and 180 in the HT-FET group. There were no significant differences in obstetric complications and perinatal outcomes between the two groups. The NC-FET group had significantly higher serum levels of P4 (17.2 ng/mL vs 8.85 ng/mL; p < 0.0001) but not E2 (144 pg/mL vs 147 pg/mL; p = 0.69) on the day of ET. Additionally, 3 days after ET, the NC-FET group had significantly higher levels of both E2 (171 pg/mL vs 140.5 pg/mL; p = 0.0037) and P4 (27.3 ng/mL vs 11.7 ng/mL; p < 0.0001) compared with the HT-FET group. CONCLUSION: Our study revealed that although there were significant differences in E2 and P4 levels around implantation between the two groups, there were no significant differences in obstetric complications and perinatal outcomes. Therefore, the hormonal environment around implantation did not appear to be the primary cause of differences in obstetric and perinatal outcomes between the two EM preparation methods used in FET.

Effect of extra-low dose levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: This study was undertaken to test the therapeutic effect of extra-low dose of levothyroxine (LT4; 25 mcg/day) to preconception and pregnant women with subclinical hypothyroidism (SCH). MATERIALS AND METHODS: This is a retrospective study, SCH women who succeeded in their first in vitro fertilization (IVF) cycle between January 1, 2018, to December 31, 2020 were included. SCH is defined as normal serum free thyroxine (T4) level and an elevated serum thyroid stimulating hormone (TSH) level >4 mIU/L. Extra-low dose of levothyroxine (LT4; 25 mcg/day) was prescribed to the SCH women from the establish of diagnosis of SCH to the end of pregnancy. The pregnancy outcomes (miscarriage, live birth, preterm birth, and small for gestational age baby) were compared to the euthyroid pregnant women. RESULTS: Totally, 589 women were screened, and 317 cases received their first time IVF treatment. 167 women were clinically pregnant after IVF treatment, 155 of them were euthyroid and 12 of these women were diagnosed to have SCH. The average age of the participants was 35 years old. There were no significant differences in age, body mass index (BMI), anti-müllerian hormone (AMH), types of embryo transfer, number of embryos to transfer, or embryo stage during transfer between two groups. The live birth rate, miscarriage rate, and preterm birth rate in women with SCH supplemented with extra-low dose of LT4 were non-inferior to euthyroid patients (miscarriage rate: P = 0.7112; live birth rate: P = 0.7028; preterm delivery: P = 0.2419; small for gestational age: P = 0.2419). CONCLUSION: Our result demonstrated that supplementation with extra-low dose of levothyroxine at 25 mcg/day to SCH women can produce the comparable obstetrical and neonatal outcome as that in euthyroid pregnant women. Accordingly, we suggest extra-low-dose of levothyroxine may be considered as a safe and effective alternative for those SCH pregnant women who were not tolerated to the standard dose of levothyroxine.

Localization Patterns of RAB3C Are Associated with Murine and Human Sperm Formation.

Background and Objectives: Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the cytoskeleton. Polymerization of SEPTs contributes to several critical cellular processes such as cytokinesis, cytoskeletal remodeling, and vesicle transportation. In our previous study, we found that SEPT14 mutations resulted in teratozoospermia with >87% sperm morphological defects. SEPT14 interactors were also identified through proteomic assays, and one of the peptides was mapped to RAB3B and RAB3C. Most studies on the RAB3 family have focused on RAB3A, which regulates the exocytosis of neurotransmitters and acrosome reactions. However, the general expression and patterns of the RAB3 family members during human spermatogenesis, and the association between RAB3 and teratozoospermia owing to a SEPT14 mutation, are largely unknown. Materials and Methods: Human sperm and murine male germ cells were collected in this study and immunofluorescence analysis was applied on the collected sperm. Results: In this study, we observed that the RAB3C transcripts were more abundant than those of RAB3A, 3B, and 3D in human testicular tissues. During human spermatogenesis, the RAB3C protein is mainly enriched in elongated spermatids, and RAB3B is undetectable. In mature human spermatozoa, RAB3C is concentrated in the postacrosomal region, neck, and midpiece. The RAB3C signals were delocalized within human spermatozoa harboring the SEPT14 mutation, and the decreased signals were accompanied by a defective head and tail, compared with the healthy controls. To determine whether RAB3C is involved in the morphological formation of the head and tail of the sperm, we separated murine testicular tissue and isolated elongated spermatids for further study. We found that RAB3C is particularly expressed in the manchette structure, which assists sperm head shaping at the spermatid head, and is also localized at the sperm tail. Conclusions: Based on these results, we suggest that the localization of RAB3C proteins in murine and human sperm is associated with SEPT14 mutation-induced morphological defects in sperm.

Artificial intelligence model to predict pregnancy and multiple pregnancy risk following in vitro fertilization-embryo transfer (IVF-ET).

OBJECTIVE: To decrease multiple pregnancy risk and sustain optimal pregnancy chance by choosing suitable number of embryos during transfer, this study aims to construct artificial intelligence models to predict the pregnancy outcome and multiple pregnancy risk after IVF-ET. MATERIALS AND METHODS: From Jan 2010 to Dec 2019, 1507 fresh embryo transfer cycles contained 20 features were obtained. After eliminating incomplete records, 949 treatment cycles were included in the pregnancy model dataset and 380 cycles in the twin pregnancy model dataset. Six machine learning algorithms were used for model building based on the dataset which 70% of the dataset were randomly selected for training and 30% for validation. Model performances were quantified with the area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. RESULTS: Models built with XGBoost performed best. The pregnancy prediction model produced accuracy of 0.716, sensitivity of 0.711, specificity of 0.719, and AUC of 0.787. The multiple pregnancy prediction model produced accuracy of 0.711, sensitivity of 0.649, specificity of 0.740, and AUC of 0.732. CONCLUSIONS: The AI models provide reliable outcome prediction and could be a promising method to decrease multiple pregnancy risk after IVF-ET.

HLA sharing and maternal HLA expression in couples with recurrent pregnancy loss in Taiwan.

OBJECTIVE: The aim of this study is to investigate the frequency and distribution of human HLA sharing and maternal HLA allele expression in couples with recurrent pregnancy loss in Taiwan. MATERIALS AND METHODS: We retrospectively reviewed couples experienced two or more pregnancy loss before 20th weeks of gestation from March 2014 to November 2020 having HLA determination. Fertile individuals with one or more live-birth offspring receiving HLA allele determination during the same period were included as the control group. The distribution and frequency of HLA sharing were analyzed and presented by descriptive statistics. Fisher Exact Test were used to analyze specific maternal and paternal HLA allele comparing individuals with RPL to fertile group. P-value < 0.05 was thought to be statistically significant. RESULTS: 72 couples were enrolled from March 2014 to November 2020. Regarding the distribution of HLA sharing, HLA sharing between females and their male partners less and equal to 2 pairs were found in 40.3% of the couples. HLA sharing greater and equal to 3 pairs are found in 59.8% couples. HLA sharing was most frequently found in alleles HLA-A02, A11, DQ07, C07 and B60 in descending order. There was a significant lower expression of HLA-B13 in women with RPL compared to women who had successful pregnancy (p = 0.0234). Compared infertile men with fertile men cohort, the frequency of HLA-DR04 (p = 0.0438, OR 2.444, 95% CI 1.0251-5.8287), HLA-DR12 (p = 0.001, OR 30.85, 95% CI 4.0296-236.19) and HLA-15 (p = 0.0357, OR 9.354, 95% CI 1.1610-75.37) were found to be significantly higher in men with RPL. On the contrary, HLA-DR07 (p = 0.0085, OR 0.124, 95% CI 0.0264-0.587) and HLA-DR10 (p = 0.0395, OR 0.048, 95% CI 0.0027-0.8641) were found to be significantly lower in men with RPL. CONCLUSION: We found a tendency to recurrent pregnancy loss in couples with more than 2 pairs of HLA sharing. The similarity of HLA sharing, the expression of maternal HLA-B13 allele and paternal HLA-DR alleles in Taiwanese couples might play a role in recurrent pregnancy loss.

Severe Postpartum Hemorrhage Complicated with Liver Infarction Resulting in Hepatic Failure Necessitating Liver Transplantation.

Postpartum hemorrhage remains a major threat to maternal health. Intervention after critical blood loss or development of disseminated intravascular coagulation may lead to disastrous organ failure and poor outcomes. A 30-year-old woman was transferred to our emergency department due to massive postpartum hemorrhage. Shock and disseminated intravascular coagulation ensued, and the patient's condition quickly deteriorated. We performed an emergency hysterectomy, but blood loss had been massive. Moreover, there was another episode of internal bleeding that led to further blood loss. Ischemic injury to the liver was tremendous, with resulting progressive jaundice and hepatic encephalopathy. The patient required liver transplantation. Imaging studies and operative findings showed a large area of hepatic infarction. Unfortunately, the patient died of intractable sepsis shortly after liver transplantation. Disseminated intravascular coagulation and resultant hepatic infarction combined with ischemic hepatitis were the direct cause of death in our case.

Acute abdomen in early pregnancy due to ovarian torsion following successful in vitro fertilization treatment.

OBJECTIVE: Ovarian torsion is an acute abdomen requiring prompt intervention. Ovarian torsion seldom occurs during pregnancy. However, with in vitro fertilization (IVF) treatments, ovarian hyperstimulation may increase the size of the ovaries and result in the occurrence of adnexal torsion. Here, we report two cases of ovarian torsion after IVF and discuss the optimal management of this emergency medical condition. CASE REPORT: The first case was a 23-year-old woman who received IVF-embryo transfer due to tubal factor infertility. Sudden-onset, lower abdominal pain developed at the 6th week of pregnancy. Conservative treatment with antibiotics was the initial approach, but a right oophorectomy had to be performed due to right ovarian torsion with hemorrhagic and gangrenous changes. The second case was a 38-year-old woman diagnosed with bilateral ovarian torsion at 8 weeks' gestation due to the sudden onset of low abdominal pain. Laparoscopy was arranged immediately after the diagnosis was confirmed. The left ovary was successfully preserved due to prompt intervention. Both pregnancies continued without problems after surgery. CONCLUSION: Ovarian hyperstimulation during IVF-embryo transfer treatment is a risk factor for developing adnexal torsion. Early diagnosis and prompt surgical intervention is the only way to protect the ovary and preserve the pregnancy. Laparoscopic surgery in early pregnancy causes no harm to the fetus and should be encouraged once the diagnosis is confirmed. Delaying surgery may induce serious infection and jeopardize the lives of both the fetus and mother.

Alpha-lipoic acid prevents endotoxic shock and multiple organ dysfunction syndrome induced by endotoxemia in rats.

Alpha-lipoic acid (ALA), a naturally occurring disulfide derivative of octanoic acid, serves as a strong antioxidant and has been reported to possess anti-inflammatory effects. The aim of the present study is to investigate the preventive and therapeutic effects of ALA on multiple organ dysfunction syndrome (MODS) caused by endotoxemia in rats. Male Wistar rats were intravenously infused with lipopolysaccharide (LPS) (10 mg/kg) to induce endotoxemia. Alpha-lipoic acid 10, 20, or 40 mg/kg was administered intravenously 60 min before (pretreatment) LPS challenge, and ALA 40 mg/kg was administered intravenously 30 min after (posttreatment) LPS challenge. Pretreatment and posttreatment with ALA significantly improved the deleterious hemodynamic changes 8 h after LPS challenge, including hypotension and bradycardia. Alpha-lipoic acid reduced the plasma levels of glutamic pyruvic transaminase, blood urea nitrogen, lactate dehydrogenase, tumor necrosis factor-α, nitric oxide metabolites, and thrombin-antithrombin complex, which increased markedly after LPS challenge. The induction of inducible nitric oxide synthase both in the liver and the lung and vascular superoxide anion production were also significantly suppressed by ALA. Moreover, ALA significantly attenuated LPS-induced caspase-3 activation in cardiomyocytes and improved survival rate. In conclusion, ALA effectively attenuated LPS-induced acute inflammatory response and improved MODS. The antioxidant and anti-inflammatory effects of ALA may contribute to these beneficial effects. Alpha-lipoic acid might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS and inflammatory vascular diseases.

The cardioprotective effect of hypertonic saline is associated with inhibitory effect on macrophage migration inhibitory factor in sepsis.

Sepsis can cause myocardial dysfunction, which contributes to the high mortality of sepsis. Hypertonic saline (HS) has been reported to increase myocardial contractility in sepsis. In the present study, mechanisms of action of HS resuscitation (4 mL of 7.5% NaCl per kilogram) on cardiac function have been evaluated in septic rats. HS was administered 1 h after LPS (10 mg/kg, i.v.) challenge. The mean arterial blood pressure significantly decreased 4 h after LPS challenge, and septic shock was observed at the end of experiment (6 h). Posttreatment with HS prevented hypotension caused by LPS and significantly improved cardiac function, evidenced by increases in left ventricular developed pressure, mean +dP/dt and -dP/dt. The amplitude of electrical-stimulated intracellular Ca(2+) transient in isolated single cardiomyocytes was significantly reduced after 6 h LPS insult, which was recovered by HS. In addition, LPS resulted in significant increases in neutrophil myeloperoxidase activity, macrophage migration inhibitory factor (MIF), and NF-κB phospho-p65 protein levels in myocardium at 6 h, which were significantly attenuated by HS. In conclusion, HS improved myocardial contractility and prevented circulatory failure induced by endotoxemia, which may attribute to improvement of intracellular calcium handling process and inhibitory effects on neutrophil infiltration and MIF production in hearts.

Comparison of the effect of two different doses of recombinant gonadotropin for ovarian stimulation on the outcome of intrauterine insemination.

OBJECTIVE: The aim of this study was to identify an optimal stimulation protocol for intrauterine insemination (IUI) to obtain an acceptable pregnancy rate and low frequency of multiple pregnancies. MATERIALS AND METHODS: In total, 340 patients, who received intrauterine insemination because of ovulation dysfunction, were enrolled in this study. Group I consisted of 203 patients who received recombinant FSH (r-FSH) 150U every other day as an ovulation induction agent. Group II consisted of 137 patients who received r-FSH 100U every other day as an ovulation induction agent. All patients in both groups also received clomiphene citrate 100 mg/day for consecutive five days from the fifth day of the cycle. Only patients with at least two follicles >18 mm on the human chorionic gonadotropin injection days were included in this study. RESULTS: The clinical pregnancy rate was 14.8% (30/203) in Group I compared with 20.4% (28/137) in Group II, p > 0.05. The incidence of multiple pregnancy was 41.7% (10/24) in Group I compared with 12.5% (3/24) in Group II, p < 0.05. CONCLUSIONS: The concurrent use of low-dose r-FSH and clomiphene citrate would seem not only to be cost-effective but also highly satisfactory in that it prevents high-order multiple pregnancies.

Cardioprotective effects of long-term treatment with raloxifene, a selective estrogen receptor modulator, on myocardial ischemia/reperfusion injury in ovariectomized rats.

OBJECTIVE: The aim of this study was to investigate the beneficial effect of long-term treatment with raloxifene (RAL), a selective estrogen receptor modulator, on myocardial ischemia/reperfusion (MI/R) injury in ovariectomized (Ovx) rats. METHODS: Ovariectomy was performed in female Sprague-Dawley rats 8 weeks old. Ovx rats were treated with RAL 1 or 5 mg/kg (gavage, once daily) or 17beta-estradiol (E2; 50 microg/kg SC, three times a week) for 8 weeks. The cardioprotective effect of RAL was evaluated in an open-chest anesthetized rat model of MI/R, which was induced by 40-minute left coronary artery occlusion and 100-minute reperfusion. RESULTS: Long-term treatment with RAL 1 mg/kg significantly suppressed the duration of ventricular tachycardia elicited by MI. After MI/R, the levels of plasma creatine kinase-MB fraction and lactate dehydrogenase in Ovx rats were significantly higher than those in the sham group, which were significantly reduced by long-term treatment with RAL 1 mg/kg or E2. Neutrophil myeloperoxidase activity in ischemic myocardium markedly increased in the Ovx group, whereas long-term treatment with RAL 1 or 5 mg/kg or E2 significantly suppressed the elevation of myeloperoxidase activity. After MI/R, the protein expression of phosphorylated inhibitory kappaBalpha and caspase-3 in ischemic myocardium pronouncedly increased in the Ovx group and was attenuated by long-term treatment with RAL 1 mg/kg or E2. CONCLUSIONS: Long-term treatment with RAL can reduce the severity of MI-induced arrhythmias and attenuate MI/R-induced damages and apoptosis in Ovx rats. This cardioprotective effect of RAL may be associated with inhibition of neutrophil infiltration and suppression of nuclear factor-kappaB activation.

Major complications of operative gynecologic laparoscopy in southern Taiwan: a follow-up study.

STUDY OBJECTIVES: This follow-up study examined the major complications among 4307 operative gynecologic laparoscopies. The overall complication rate and each individual category were compared with those of our previous study period. The clinical outcome and salvage procedures were correlated with the time of recognition and the severity of initial procedures in the individual injury type. DESIGN: Retrospective, comparative study based on medical record reviewing (Canadian Task Force classification II-3). SETTING: Tertiary teaching hospital, Chi Mei Foundation Hospital in southern Taiwan. PATIENTS: Records of women (n = 4307) aged 40.5 +/- 11.7 years (mean +/- SD [95% CI 40.1-40.5]) who underwent operative gynecologic laparoscopies from January 2000 through February 2006 were reviewed in this study. The complications were compared with those of our previous study based on 1507 laparoscopies performed between December 1992 and November 1999 for follow-up comparison. INTERVENTIONS: Gynecologic laparoscopic surgeries. MEASUREMENTS AND MAIN RESULTS: Thirty-four complications occurred in 31 patients requiring repair procedures, 3 of whom had multiple complications, with an overall complication rate of 0.72% (31/4307). There were 13 bladder injuries (0.30%), 7 bowel injuries (0.16%), 3 cases of internal bleeding (0.07%), 4 vaginal stump hematomas or abscesses (0.09%), 3 ureteral injuries (0.07%), 3 major vessel injuries (0.07%), and 1 trocar site hematoma (0.02%). In addition, there were 125 (2.88%) postoperative blood transfusions without additional operative intervention. The major complication rate decreased compared with that of the previous study (0.72% [95% CI 0.51%-1.02%] vs 1.59% [95% CI 1.07%-2.36%]; p = .005). The overall complication rates were not significantly different between laparoscopic hysterectomy (LH) group and non-LH group. However, bladder injury happened more frequently in the LH group, whereas bowel injury was more common in the non-LH group. In addition, the severity of the original injury, timing of recognition, and accompanying salvage procedures correlated with the clinical outcomes. CONCLUSION: The significantly decreased major complication rate, as compared with that of our previous study period, confirms the importance of experience accumulation and use of preventive maneuvers in reducing the complication rate. There were no significant differences among the individual injury category during these 2 study periods. The manifestations of bowel injury were highly variable and individualized. The accumulation of surgical experience with the aid of preventive maneuvers is helpful to reduce the complication rate significantly.

Influence of pituitary suppression with triphasic or monophasic oral contraceptives on the outcome of in vitro fertilization and embryo transfer.

PURPOSE: To compare the clinical outcome of IVF treatment after pituitary suppression with two different oral contraceptives (OCs). METHODS: 65 patients who received IVF treatment was classified into 2 groups based on the difference of OCs they used for pituitary suppression before ovarian hyperstimulation. Group 1 included 36 patients who received monophasic OCs. Group 2 included 29 patients who received triphastic OCs. Both groups received the OCs from the 5th day of the cycle for consecutive 21 days. The hormone profiles after OCs and clinical outcome of IVF treatment were compared between two groups. Two-sample t-tests and X2 tests were used for statistical analyses. P < 0.05 was considered statistically significant. RESULTS: The mean age and basal hormone profiles were comparable between two groups. After ovulation suppression with different OCs, the day 2 FSH and LH value revealed statistically significant difference between two groups(4.2+/-1.8 vs 6.0+/-2.6; 2.7+/-2.0 vs 4.2+/-3.3 respectively). The numbers of oocyte per retrieval and fertilization rate were comparable between two groups, but higher quality embryos as revealed by the cleavage speed were noted in the triphastic OCs group. Although statistically not significant, higher implantation rate and pregnancy rate were also noted in the triphastic OCs group. CONCLUSIONS: Different OCs for pituitary suppression can result in different hormone profiles. Ovulation induction in IVF treatment should be individualized according to these hormone changes to achieve the optimal clinical outcome. Triphastic OCs exceeds monophastic OCs in producing good quality embryo in IVF-ET treatment.

Endometrioma undergoing laparoscopic ovarian cystectomy: its influence on the outcome of in vitro fertilization and embryo transfer (IVF-ET).

PURPOSE: To evaluate the effect of laparoscopic ovarian cystectomy for endometrioma on the clinical outcome of IVF treatment. METHODS: Patients who received IVF treatment were retrospectively classified into two groups. Group 1 included 95 patients who received IVF due to tubal occlusion. Group 2 included 127 patients who had received laparoscopic ovarian cystectomy for endometrioma(s) followed by IVF treatment. Clinical outcomes of IVF treatment were compared between two groups. RESULTS: More oocytes were harvested per retrieval in Group 1 than Group 2 (p < 0.05). The fertilization rate was higher in Group 1 than Group 2 (p < 0.05). Although the implantation rate was higher in Group 2 (p < 0.05), the clinical pregnancy rate revealed no statistically significant difference between the two groups. CONCLUSIONS: Women who received ovarian cystectomy for endometriomas have fewer oocytes harvested during IVF treatment. However, their chance of pregnancy was comparable to patients with tubal problems who underwent IVF treatment.

Vaginal disinfection with povidone iodine immediately before oocyte retrieval is effective in preventing pelvic abscess formation without compromising the outcome of IVF-ET.

PURPOSE: In this study, the method of employing preretrieval vaginal douching with aqueous povidone iodine is examined to see if it can decrease the incidence of pelvic abscess without compromising the clinical outcome of IVF-ET. METHODS: Patients with ovarian endometrioma and received IVF-ET treatment were retrospectively classified into two groups according to the difference of vaginal douching solution immediately before oocyte retrieval. RESULTS: There was no difference in the fertilization rate (81.2% versus 79.8%, P > 0.05), implantation rate (19.2% versus 23.3%, P > 0.05), clinical pregnancy rate (39.3% versus 46.2%, P > 0.05) between the two groups. There was no infection in patients of group two but two cases in group one developed pelvic abscess and needed surgical intervention. CONCLUSIONS: Vaginal douching with aqueous povidone iodine followed by normal saline irrigation immediately before oocyte retrieval is effective in preventing the pelvic infection without compromising the outcome of IVF treatment.

Laparoscopic surgery for omental pregnancy.

A 16-year-old girl underwent emergency laparoscopic surgery for what was thought to be hematoperitoneum secondary to extrauterine pregnancy. During the operation, omental pregnancy was diagnosed and treated by laparoscopy. According to Studiford's criterion, this case can be classified as a primary omental pregnancy. When performing laparoscopy for suspected tubal pregnancy with no visible pathologic changes on either tube, careful evaluation of the whole abdominal cavity is necessary so as not to overlook an abdominal pregnancy.