Impact of COVID-19 Pandemic on Clinical and Embryological Outcomes of Assisted Reproductive Techniques.

Background: The emergence of the COVID pandemic unfolded a series of precautions and dilemmas and the complete suspension of health services. With the gradual emergence of data showing near minimal effects of the virus on pregnancy, Assisted Reproductive Techniques (ART) services were gradually resumed following guidelines and advisories. Aim: The purpose of this study was to detect the COVID positivity rate in women undergoing ART treatment during the COVID pandemic and compare clinical and embryological outcomes to the ART cycles performed in the pre-COVID era. Study Setting and Design: This was a retrospective cohort study of all women undergoing controlled ovarian stimulation, followed by a fresh or frozen embryo transfer (ET) between 1st October 2019 and 31st March 2020 (control group) and between 1st April 2020 and 31st September 2020 (study group) at Nova IVF Fertility Clinic, Ahmedabad. Material and Methods: The study group underwent ART during the first wave of COVID-19 pandemic in India and when gradual unlocking of facilities including ART was advised as per the national ART advisory by the ICMR in December 2020. The outcomes were compared with the control group (cycles in pre-covid time). Statistical Analysis: Statistical analysis was performed in SPSS (v25.0) and included Mann-Whitney U, Fisher's exact and Pearson Chi-square as appropriate. Values of P < 0.05 were considered statistically significant. Results: A total of 367 in vitro fertilisation (IVF) stimulations were initiated. A total of 342 retrievals and 606 ETs (171 fresh and 435 frozen) were completed during the study period with a COVID positivity rate of 6.8% (25/367) amongst fresh and 3.9% (18/453) amongst frozen ETs, respectively; the PR and IR in the study group was similar to the control group (47.6 vs. 55.1 P = 0.4 and 68.7 vs. 66.4; P = 0.52, respectively). The maternal complication rates were similar in both groups with a COVID positivity rate of 10.2% (23/225) and 1 maternal death in the study group. The live birth rates were similar. Conclusions: We did not find a noteworthy difference in the clinical and embryological outcomes in the IVF cycles conducted in the COVID era as compared to the pre-COVID time. Thus, with adequate precautions and safety measures, ART services conducted during the COVID pandemic have comparable birth outcomes and can be safely advocated.

Follicular phase cycle programming using estradiol in oocyte donors-a convenient and effective approach.

Objective: To study the efficacy of estradiol for cycle programming in oocyte donors when administered in the follicular phase only. Design: Prospective interventional study. Setting: Single fertility center. Patients: Ninety-three oocyte donors underwent programmed stimulation using estradiol in the follicular phase. Their previous unprogrammed cycles were used as historical controls. Interventions: Donors received 8 mg of estradiol hemihydrate from day 2 till 1 day before the start of stimulation. Main Outcome Measures: The primary outcome measures studied were the number of oocytes retrieved, duration of stimulation, and total gonadotropin dose. The number of mature oocytes, oocyte maturation rate, fertilization rate, blastulation rate, implantation rate, and pregnancy rate were the secondary outcomes. Results: The average number of oocytes retrieved was higher in the study group (36.4 vs. 32.5). The duration of stimulation (9.22 vs. 9.21 days) and the total gonadotropin dose were similar (3,085.5 vs. 3,026 IU) between both groups. The mean number of mature oocytes retrieved was higher in the study group (30.1 vs. 26.3), but the maturation rate was similar (84.6% vs. 81.2%). The fertilization rate (77.8% vs. 78.7%), number of blastocysts, blastulation rate (32.7% vs. 33.2%), implantation rate (59.3% vs. 66.3%), and pregnancy rate (77.3% vs. 77.1%) showed no statistically significant difference. Conclusions: Estradiol usage in the follicular phase alone is an effective and convenient option for cycle programming in oocyte donors. It can yield similar mature oocytes and does not affect the clinical outcomes. Further larger sample-sized studies may be needed to validate its use which can also be extended to routine in vitro fertilization cycles. Clinical Trials Registration Number: CTRI/2020/09/027815.

A Comparative Study to Assess the Efficacy of Two Different Estradiol Formulations during In Vitro Fertilization.

Improvements in stimulation protocols, introduction of vitrification, and changes in clinical practices have contributed to improved efficacy and safety of assisted reproductive technology (ART) procedures. This has also led to a concomitant increase in number of cycles requiring hormone replacement therapy (HRT) protocol for performing an embryo transfer. Successful implantation is dependent on endometrial thickness which in turn is regulated by temporal regulation of hormones. Careful control of estrogen levels determines uterine receptivity. One of the most used drugs for achieving appropriate endometrial lining of >7 mm in HRT is estradiol valerate. Although different estrogen formulations with varying physicochemical properties exist, there is not enough literature to support if the differences translate into a discernible clinical outcome in an in vitro fertilization (IVF) setting. Objective and Method. In this study, retrospective in nature, we compare the efficacy of oral estradiol hemihydrate with estradiol valerate in HRT cycles in 2,529 Indian women, undergoing treatment at a center in India between Jan 2017 and May 2019. Results. Our results primarily indicate that between the estradiol valerate and estradiol hemihydrate treatment groups, the implantation rate (IR) was 47.42% and 49.07%, respectively (P value 0.284), and the endometrial thickness (mean ± SEM in mm) that was achieved was 9.25 ± 0.038 mm and 9.57 ± 0.058 mm (P value < 0.001), respectively. There were no significant differences observed in the secondary outcome measures including clinical pregnancy rate, abortion rate, ectopic pregnancy, and live birth rate. Conclusions. Hence, this study concludes that oral estradiol hemihydrate and estradiol valerate are therapeutically equivalent and provide similar clinical outcomes in an IVF setting.

Chemotherapy Can Interfere in Implantation in In-vitro Fertilization.

Improvement in cancer treatments has allowed more women to plan a pregnancy once the disease is cured. The effects of chemotherapy on ovaries are well proven but those on the uterus, especially the endometrium and embryo implantation are still unknown. Usage of newer tyrosine kinase inhibitors such as nilotinib has revolutionized the management of leukemias. Although nilotinib has been reported to be safe in pregnancy, further studies are needed to evaluate its effect on the process of embryo implantation, especially in women undergoing in-vitro fertilization. We report a case where successful pregnancy outcome was achieved after stoppage of nilotinib before embryo transfer in a woman who had previous four failed attempts while on nilotinib and no other obvious cause of implantation failure. Despite optimal endometrial thickness and receptivity, the pale appearance of endometrium on hysteroscopy was attributed to be a possible effect of nilotinib and prompted us to withhold it.

Genital Micro-Organisms in Pregnancy.

The microbiome of the female genital tract may undergo changes in pregnancy due to metabolic, endocrinological, and immunological alterations. These dysbiotic states may cause infections which may ascend upwards to the feto-placental unit or may be seeded hematogenously. These low grade and often low virulent infectious states lead to chronic inflammatory states and maybe associated with adverse maternal and neonatal outcome. Organisms have been isolated from amniotic fluid and placentae from women delivering pre-term; however the possibility of contamination cannot be conclusively ruled out. Common vaginal dysbiotic states often cause symptoms that are overlooked and often untreated. Vulvovaginal Candidiasis (VVC), Bacterial Vaginosis (BV), and Trichomonas Vaginitis (TV) are the commonly occurring dysbiotic states leading to vaginal infective states in pregnancy. With the advent of novel technologies like Next Generation sequencing (NGS), it will soon be possible to comprehensively map the vaginal microbiome and assess the interplay of each microbial state with their effects in pregnancy. This may open new avenues for antibiotic recommendations, probiotics and potential alternate therapies for dysbiotic states leading to pregnancy complications.

Maternal and Neonatal Complications in Twin Deliveries as Compared to Singleton Deliveries following In vitro Fertilization.

BACKGROUND: Twin pregnancy is an iatrogenic complication following in vitro fertilization (IVF) that can be decreased using elective single-embryo transfer. However, the risks associated with twin pregnancy following IVF as compared to singleton IVF pregnancy need to be further evaluated. AIM: This study aims to compare the maternal, perinatal, and neonatal complications in singleton and twin pregnancies following IVF-intracytoplasmic sperm injection (ICSI). Settings and Design: Retrospective observational cohort study using previously collected routine patient data. MATERIALS AND METHODS: Singleton and twin deliveries following IVF/ICSI from January 2014 to August 2015 were included. Data were collected from patient records and the obstetricians of the patients. STATISTICAL ANALYSIS USED: SPSS was used for analysis. Student's t-test and Fisher's exact test were used for continuous and categorical data, respectively. Significance was kept at 0.05. RESULTS: There were 897 singleton and 382 twin deliveries (total of 1661 babies). The mean gestational age at delivery was lower in twin deliveries (34.9 ± 3.1 weeks) as compared to singleton deliveries (36.8 ± 3.2 weeks, P < 0.001). The overall incidence of maternal complications was higher in twin pregnancies (29.3% vs. 21.3%, odds ratio = 1.53, 95% confidence interval = 1.17-2.01; P = 0.003). The mean birth weight of babies was significantly lower (2.02 ± 0.58 kg vs. 2.71 ± 0.68 kg; P < 0.001) and the incidence of stillbirth plus neonatal death was higher (7.5% vs. 4.6%, P = 0.01) in the twin group as compared to the singleton group. CONCLUSION: Twin deliveries, following IVF/ICSI deliver at lower gestational age, have lower birth weight and have higher odds of stillbirth plus neonatal death as compared to singleton deliveries following IVF/ICSI.

Prediction and analysis of COVID-19 positive cases using deep learning models: A descriptive case study of India.

In this paper, Deep Learning-based models are used for predicting the number of novel coronavirus (COVID-19) positive reported cases for 32 states and union territories of India. Recurrent neural network (RNN) based long-short term memory (LSTM) variants such as Deep LSTM, Convolutional LSTM and Bi-directional LSTM are applied on Indian dataset to predict the number of positive cases. LSTM model with minimum error is chosen for predicting daily and weekly cases. It is observed that the proposed method yields high accuracy for short term prediction with error less than 3% for daily predictions and less than 8% for weekly predictions. Indian states are categorised into different zones based on the spread of positive cases and daily growth rate for easy identification of novel coronavirus hot-spots. Preventive measures to reduce the spread in respective zones are also suggested. A website is created where the state-wise predictions are updated using the proposed model for authorities,researchers and planners. This study can be applied by other countries for predicting COVID-19 cases at the state or national level.

Volume, conductivity, and scatter parameters of leukocytes as early markers of sepsis and treatment response.

INTRODUCTION: Morphologic changes in the size and granularity of leukocytes seen in sepsis could be measured using the volume, conductivity, and scatter (VCS parameters) from the automated hematology analyzers. The objective of this study is to find the clinical usefulness of VCS parameters as possible indicators of sepsis and to determine the effect of treatment on these parameters. METHODS: This observational study was conducted in a tertiary level hospital in India. Hemogram and VCS parameters obtained from LH 750 (Beckman coulter, Fullerton, CA) from 134 proven blood culture-positive cases of sepsis were reviewed on the day of culture positivity (day 0), day 3, and day 7 were analyzed and compared with those of samples from otherwise healthy 100 participants. Statistical analysis of data was done, and cutoff value was established using receiver-operator characteristic curve. RESULTS: Out of 134 culture-positive cases, 55.2% (n = 74) Gram-negative and 44.8% (n = 60) Gram-positive bacteria were isolated. The mean neutrophil volume (MNV) and mean monocyte volume (MMV) were higher in the sepsis group compared to that of the control group (165.43 ± 18.21 vs. 140.59 ± 7.6, P = 0.001 for MNV and 179.8 ± 14.16 vs. 164.54 ± 9.6, P = 0.001 for MMV). A significant decrease in MNV and MMV was observed with the initiation of the treatment. Significant changes in scatter and conductivity parameters were also noticed. A cutoff value of 150.2 for MNV gave a sensitivity and specificity of 79.1% and 95%, respectively, with an area under the curve (AUC) of 92.3%. With a cutoff of 168.3, MMV had a sensitivity of 80.6% and specificity of 77.5%, AUC of 83%. CONCLUSION: VCS parameters such as MNV and MMV can be easily obtained by an automated hematology analyzer and could be used for early detection and therapeutic response in sepsis.

Unusually Low Serum Alkaline Phosphatase Activity in a Patient with Acute on Chronic Liver Failure and Hemolysis.

A 28-year-old male with acute on chronic liver failure (ACLF) and hepatic encephalopathy had deranged liver function with curiously low level (0-15 IU/L) of serum alkaline phosphatase (ALP). Peripheral smear examination suggested hemolytic anemia. The finding of persistent low ALP, after ruling out pre-analytical causes, in ACLF has been reported in Wilson's disease (WD) with/ without autoimmune hemolytic anemia (AIHA). Definitive evidences of WD were not seen in our case. Positive DCT and histological features suggest a diagnosis of autoimmune hepatitis with secondary hemochromatosis and cholangitis. Low ALP might not always be a determinant of bile duct pathology in patients of ACLF with AIHA.

Serum S100B levels in patients with depression.

BACKGROUND: The biochemical basis of depression has been related to blood-brain barrier (BBB) allowing/restricting a number of components to enter the brain milieu from the peripheral plasma milieu. S100B has been associated with BBB damage and is used as a marker of its integrity. Several studies have reported that depressive patients have increased levels of S100B in serum and cerebrospinal fluid. MATERIALS AND METHODS: Forty-two confirmed cases of depression, 13-25 years of ages were recruited from the Department of Psychiatry, All India Institute of Medical Sciences during the period from January 2013 to June 2014 along with 42 healthy controls of comparable age and sex. Psychometric evaluation of the patients and controls was done to assess the severity of depression using Beck's Depression Inventory-II and Hamilton Depression Rating Scale. Medical assessment and laboratory investigations were done. Serum S100B levels were measured using Sandwich ELISA. The results obtained were statistically analyzed. RESULTS: Levels of serum S100B were significantly elevated in patients with major depression as compared to controls. Significantly higher levels of S100B were seen only in females as compared to their healthy counterparts. Serum S100B was higher in depressed participants with the recurrent disorder than those with single episode. No correlation of levels of this marker was seen with clinical severity of the patients. It was found that with increased duration of illness for which the patient was being treated with antidepressants, the patients had higher levels of S100B. CONCLUSIONS: Serum S100B can be used as a biomarker of depression.

Prevalence of structural birth defects in IVF-ICSI pregnancies resulting from autologous and donor oocytes in Indian sub-continent: Results from 2444 births.

INTRODUCTION: This study was conducted to evaluate and compare the incidence of birth defects in In-Vitro Fertilization-Intra Cytoplasmic Sperm Injection (IVF-ICSI) pregnancies with autologous and donor oocytes. As a secondary outcome, the prevalence of birth defects in IVF-ICSI pregnancies was compared with those from spontaneous conceptions in India. MATERIAL AND METHODS: This retrospective study included 2444 births resulting from IVF-ICSI cycles from autologous (n = 1743) and donor oocytes (n = 701) during a 3-year period in an Indian infertility center. Birth defects, if any, were noted antenatally and followed till the neonatal period, in case of live birth. RESULTS: The overall prevalence of birth defects in IVF-ICSI pregnancies in this study was 29/2444 (118.6/10 000 births) and the most common congenital anomaly was cardiac malformation (32.7/10 000 births) followed by genitourinary (28.6/10 000 births). The risks of birth defects resulting from autologous and donor oocytes did not differ (114.7/10 000 vs 128.38/10 000; P > 0.05). However, pregnancies resulting from autologous oocytes had a higher trend of gastrointestinal birth defects (20.5/10 000 births vs 0), though not statistically significant. The risk of cardiovascular birth defects resulting from IVF-ICSI pregnancies was much higher compared with the natural conceptions in India (32.7/10 000 vs 12.7/10 000 births; P = 0.03), whereas the risk of central nervous system malformations was much lower (8.1/10 000 vs 60.18/10 000 births; P = 0.005). CONCLUSIONS: Overall, there was no significant difference in birth defects resulting from IVF-ICSI with autologous or donor oocytes. The births resulting from IVF-ICSI pregnancies did not tend to have a higher rate of birth defects a compared with natural conceptions. The differences in the prevalence of certain birth defects (cardiovascular or central nervous system) reported in IVF-ICSI pregnancies may be due to improved surveillance modalities and early detection in pregnancies following IVF-ICSI. A study with larger number of sample size will give us better understanding of the prevalence of reported incidence in this study.

India's First Child using PGT-M, PGT-A and HLA Matching for Helping a Sibling having ß-Thalassemia Major.

ß-thalassemia is a common single-gene disorder in India, with hematopoietic stem cell transplantation (HSCT) being the only cure. HSCT with matched unrelated donor is less successful, whereas finding a human leukocyte antigen (HLA)-matched related donor is difficult. Preimplantation genetic testing for monogenic diseases (PGT-M) with HLA matching is a novel option to have a matched sibling for HSCT for couples having an affected child. We present the first such case report in India. A couple, both carriers of ß-thalassemia and having an affected son, underwent PGT-M with HLA matching combined with preimplantation genetic testing for aneuploidies of embryos to have a ß - thalassemia-free child. This resulted in birth of a 10/10 HLA-matched sibling.

Retained Intrauterine Bony Fragments as a Cause of Secondary Infertility in a Tertiary Level Indian Hospital.

BACKGROUND: Midtrimester surgical abortions often result in retained intrauterine fetal bones and consequent secondary infertility. AIM: To study the incidence of women presenting with retained intrauterine bones as a cause of secondary infertility in a tertiary level Indian hospital and pregnancy rates following retrieval of these fragments. SETTING AND DESIGN: Retrospective data analysis in the infertility clinic of PGIMER (Post Graduate Institute of Medical Education and Research), a tertiary level hospital of Northern India. MATERIALS AND METHODS: Women diagnosed with retained intrauterine bony fragments were subjected to hysteroscopic removal of these fragments. Incidentally diagnosed retained bones on hysteroscopy were also removed. Such women were followed for spontaneous resumption of fertility or were subjected to ovulation induction, and pregnancy rates were noted. RESULTS: Retained fetal bones accounted for 0.28% of all women with infertility and 12% (22/144) of all the uterine causes of infertility requiring an operative hysteroscopic procedure for treatment. Only 5 (27.7%) of 18 women conceived after the hysteroscopic retrieval of bony fragments: three had full-term vaginal deliveries, one had a midtrimester abortion, and one woman is in her third trimester. CONCLUSION: Despite surgical retrieval, fertility rates may be lower due to inflammatory damage to the endometrium.

Flow Cytometry in Diagnosis of Myelomatous Pleural Effusion: A Case Report.

Plasma cell myeloma is a multifocal plasma cell neoplasm associated with increased monoclonal protein in serum and/or urine. Pleural effusions in patients with myeloma are uncommon (6 %). However, effusions due to direct infiltration of the pleura by plasma cells (myelomatous pleural effusion) are extremely rare (<1 %) and usually seen with IgA myeloma. The diagnosis of such cases requires pleural fluid cytology, electrophoresis or pleural biopsy. We present a case of myelomatous pleural effusion diagnosed using flow cytometry immunophenotyping in addition to the pleural fluid cytology. A 45 year old female was diagnosed as plasma cell myeloma (IgG kappa) in 2007. She received multiple lines of therapy during the course of her treatment including thalidomide, dexamethasone, lenalidomide, bortezomib, and doxorubicin based regimens. However, the patient had progressive extramedullary disease and developed pleural effusion in 2014. Cytological examination of the pleural fluid showed degenerative changes. Few preserved areas showed mononuclear cells including morphologically abnormal plasma cells. Immunophenotyping of these cells by flow cytometry revealed a pattern indicating neoplastic plasma cells. There was expression of CD38, CD138, and CD56, with absence of CD19, CD10 and CD45. This confirmed the diagnosis of myelomatous pleural effusion. Subsequently, the patient was offered a dexamethasone, cyclophosphamide, etoposide and cisplatin based regimen but, she declined further treatment and succumbed to her disease 3 months later. Myelomatous pleural effusion is a rare complication of plasma cell myeloma. Flow cytometry can be used as an adjunctive technique in its diagnosis particularly in cases with equivocal cytology and electrophoresis findings.

Acute pancreatitis with eclampsia-preeclampsia syndrome and poor maternal outcome: two case reports and review of literature.

Acute pancreatitis in pregnancy is a rare entity and has been reported to be associated with preeclampsia in the literature. Fulminant pancreatitis may have a guarded prognosis despite intensive multidisciplinary management. Two cases of maternal mortality in women with acute pancreatitis noted in the setting of preeclampsia-eclampsia syndrome are reported here.

The magnetotransport properties of the intermetallic compound GdCu6.

We have studied the temperature and magnetic field dependence of the electrical resistivity of GdCu(6) and have co-related the results with the temperature dependence of heat capacity and magnetization. The magnetoresistance of GdCu(6) is found to be positive both in the paramagnetic and antiferromagnetic regimes. Within the antiferromagnetic regime, the magnetoresistance is very high and increases to still higher values both with increasing field and decreasing temperature. In the paramagnetic regime the magnetoresistance continues to exhibit a finite positive value up to temperatures much higher than that corresponding to the antiferromagnetic to paramagnetic phase transition. We have shown through quantitative analysis that both the temperature dependences of resistivity and heat capacity indicate the presence of spin fluctuations within the paramagnetic regime of GdCu(6). The field dependence of electrical resistivity indicates that the positive magnetoresistance in the paramagnetic phase is not related to the orbital motion of the conduction electrons in a magnetic field (the Kohler rule). In contrast, our analysis indicates that these spin fluctuations are responsible for the positive magnetoresistance observed within this paramagnetic regime. The nature of the field dependence of electrical resistivity is found to be qualitatively similar both in the antiferromagnetic and paramagnetic regimes, which probably indicates that spin fluctuations in the paramagnetic regime are of the antiferromagnetic type.

Temperature and magnetic field induced multiple magnetic transitions in DyAg(2).

The magnetic properties of the rare-earth intermetallic compound DyAg(2) are studied in detail with the help of magnetization and heat capacity measurements. It is shown that the multiple magnetic phase transitions can be induced in DyAg(2) both by temperature and magnetic field. The detailed magnetic phase diagram of DyAg(2) is determined experimentally. It was already known that DyAg(2) undergoes an incommensurate to commensurate antiferromagnetic phase transition close to 10 K. The present experimental results highlight the first order nature of this phase transition, and show that this transition can be induced by magnetic field as well. It is further shown that another isothermal magnetic field induced transition or metamagnetic transition exhibited by DyAg(2) at still lower temperatures is also of first order nature. The multiple magnetic phase transitions in DyAg(2) give rise to large peaks in the temperature dependence of the heat capacity below 17 K, which indicates its potential as a magnetic regenerator material for cryocooler related applications. In addition it is found that because of the presence of the temperature and field induced magnetic phase transitions, and because of short range magnetic correlations deep inside the paramagnetic regime, DyAg(2) exhibits a fairly large magnetocaloric effect over a wide temperature window, e.g., between 10 and 60 K.

Magnetic properties of the field-induced ferromagnetic state in MnSi.

We present results of dc magnetization measurements focusing on the magnetic properties of the field-induced ferromagnetic state in MnSi. The temperature dependence of saturation magnetization in this ferromagnetic state exhibits the signatures of both spin wave excitations and itinerant electron ferromagnetism. The Arrott plots obtained from the isothermal field dependence of magnetization, however, are found to be distinctly nonlinear and hence cannot be explained within a simple framework of itinerant electron magnetism.