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   Table of Contents - Current issue
Coverpage
July-December 2019
Volume 2 | Issue 2
Page Nos. 51-89

Online since Friday, January 31, 2020

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EDITORíS CORNER  

Resetting the “biological clock” p. 51
Nalini Mahajan
DOI:10.4103/tofj.tofj_19_19  
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REVIEW ARTICLES Top

Fertility preservation for female cancer patients by manipulating ovarian stem cells that survive oncotherapy p. 53
Deepa Bhartiya
DOI:10.4103/tofj.tofj_12_19  
Infertility and premature ovarian failure are unwanted side effects of oncotherapy in females; however, a large number of patients survive cancer due to recent advances in their management. One of the available options to restore fertility in cancer survivors is to transplant ovarian cortical tissue slices at orthotopic sites which has resulted in the birth of 130 babies. Spontaneous pregnancies have also been reported after heterotopic transplantation of cortical tissue slices which can only be explained by the presence of stem cells and paracrine support provided by transplanted ovarian slices to the nonfunctional ovary. The ovary harbors two populations of stem cells, including very small embryonic-like stem cells (VSELs) and slightly bigger ovarian stem cells (OSCs) that divide and undergo clonal expansion to form germ cell nests in adult ovary before undergoing neo-oogenesis and primordial follicle assembly. Being relatively quiescent, VSELs survive oncotherapy and can regenerate the nonfunctional ovary. Stem cells niche gets affected by oncotherapy and transplanting autologous bone marrow mesenchymal stem cells (MSCs, which provide paracrine support) have shown to normalize ovarian function in rodents with the birth of healthy pups. Similarly, transplanting of autologous MSCs in human ovary with premature ovarian failure resulted in the birth of a baby. These advances in the field of OSCs need to be put in proper context before considering making transplantation of ovarian cortical tissue at orthotopic sites as method of standard care. Transplanting autologous MSCs is safe, and efficacy to regenerate nonfunctional ovaries needs to be evaluated in clinical settings.
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Oocyte embryo and ovarian tissue freezing in endometriosis: Food for thought p. 57
Umesh Jindal, Swati Verma
DOI:10.4103/tofj.tofj_17_19  
Fertility preservation by oocyte, embryo, or ovarian tissue in females is an established technique now. In addition to oncology patients, the indications have been extended to other benign diseases such as endometriosis which carry a significant risk of decrease in ovarian reserve due to disease or therapy instituted. Fertility preservation is not without its pros and cons. All young women need to be counseled regarding the decrease in ovarian reserve with endometriosis, age and/or surgery. Fertility preservation options need to be discussed whenever immediate childbearing is not possible or desired.
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ORIGINAL ARTICLES Top

Comparing the effectiveness of intrauterine infusion of platelet-rich plasma and granulocyte-Colony-stimulating factor in frozen embryo transfer cycles p. 62
Priya Selvaraj, Kamala Selvaraj, Hamini Chandrasekar, Lakshaya Sairam
DOI:10.4103/tofj.tofj_15_19  
Aim: The aim of the study was to compare the effectiveness of intrauterine perfusion of platelet-rich plasma (PRP) and granulocyte-colony-stimulating factor (G-CSF) in improving assisted reproductive technology (ART) outcomes in women with thin endometrium and recurrent implantation failure (RIF) undergoing frozen embryo transfer (FET). Materials and Methods: The study was conducted at GG Hospital, Fertility and Women's Speciality Centre, Chennai, India, between March 2016 and September 2019. The study group comprised of 132 demographically identical women with RIF and thin endometrium undergoing FETs. The mean age of the participants in both the groups was 33.18 ± 4.30 and 32.5 ± 5.02, respectively. These women were randomly divided into PRP Group A (n = 56) and G-CSF Group B (n = 76). Both the groups were initiated with the conventional preparation for FET using estradiol valerate and micronized progesterone along with a trigger (10,000 IU of human chrionic gonadotropins (HCG)). Intrauterine PRP and G-CSF were then administered for those patients with thin endometrium (≤0.8 cm) on days 16 and 18, and sequential embryo transfers were performed as day 3 embryos along day 5 blastocyst. Results: The average endometrial thickness before the infusion of PRP and G-CSF was 0.67 ± 0.09 and 0.70 ± 0.08, whereas after the infusion, it improved to 0.78 ± 0.14 and 0.75 ± 0.06, respectively. P value between Groups A and B was 0.0968 and hence statistically not significant, indicating similar improvement by both the methods. P value for implantation rate, clinical pregnancy rate, live birth rate (LBR), and miscarriage rate was 0.182, 0.695, 0.287, and 0.270, respectively. It was found that there is no statistically significant difference in ART outcomes in both the PRP and G-CSF groups. Conclusion: Intrauterine infusion of PRP and G-CSF was beneficial in improving LBR in RIF with thin endometrium, both being statistically comparable. There were no differences to show superior of one over the other.
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The use of preimplantation genetic testing for aneuploidy and mitochondrial DNA scoring helps in improving assisted reproductive techniques outcome p. 66
Nalini Mahajan, Jasneet Kaur
DOI:10.4103/tofj.tofj_13_19  
Background: Aneuploidy is a leading cause of implantation failure and miscarriage. Preimplantation genetic testing for aneuploidy (PGT-A) with mitoscore enables screening of viable euploid embryos, thereby improving in vitro fertilization (IVF) outcome. Aim of the study: The aim of this study is to determine if the use of PGT-A in patients with valid indications can help improve assisted reproductive techniques outcome. Materials and Methodology: All patients undergoing IVF-PGT-A cycles between April 2016 and March 2018 were included (n = 42) in the study. Patients were compared with a control group consisting of fresh or frozen blastocyst transfers selected by morphology, during the same period (n = 226). Trophectoderm samples were subjected to chromosome analysis and mitoscore assessment using next-generation sequencing. Single-embryo transfer was done according to transfer priority determined by mitoscore. Statistical Analysis: The Chi-square test was used for comparisons between the study groups with respect to percentages. A value of P <0.05 was considered as statistically significant. Results: The indications for PGT-A in our patients were advanced maternal age 33%, followed by recurrent pregnancy loss 25%, recurrent implantation failure 19%, previous history of aneuploidy 16%, and severe male factor 6%. An ongoing pregnancy rate (OPR) of 61% versus 48% (P = 0.0049) was achieved with PGT-A versus controls, respectively. Thirty-two percent of patients did not have any euploid embryos for transfer. Conclusion: Offering PGT-A with mitoscore for valid indications seems to be an impressive tool to increase implantation and OPRs and helps in counseling patients for further course of treatment.
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Preimplantation genetic testing for aneuploidy and subsequent blastocyst transfer improves pregnancy outcome in advanced maternal age patients p. 74
Beena Rawat, Surleen Kaur
DOI:10.4103/tofj.tofj_14_19  
Context: Advanced maternal age (AMA) is an important parameter that negatively influences the pregnancy rate in assisted reproductive technology because the rate of aneuploidy in the embryos increases with the patient age. Aims: The aim of this study is to evaluate whether the transfer of an euploid embryo selected by preimplantation genetic testing for aneuploidy (PGT-A) would improve the pregnancy outcome in AMA patients. Settings and Design: This was a retrospective controlled study. Materials and Methods: A total of 250 patients who had undergone frozen transfers of day 5/6 blastocysts were recruited. Patients who had morphologically selected euploid blastocyst transfer were grouped under PGT-A (n = 47) and patients who had only morphologically selected blastocyst transfer were grouped under non-PGT-A (n = 203). The patients were further grouped as test group (AMA patients, ≥35 years of age) and control group (young patients, <35 years of age) in PGT-A and non-PGT-A arm. The comparison was performed between all of the groups. The primary outcome measure was serum beta-human chorionic gonadotropin level for pregnancy confirmation after 14 days of embryo transfer. Statistical Analysis Used: The Chi-square test was used to analyze pregnancy outcomes. Results: Overall pregnancy rate was found to be significantly increased in the PGT-A group in comparison to the non-PGT-A group irrespective of the age (78.5% vs. 59.7%, P = 0.00001). No significant difference were observed in Young versus AMA group of PGT-A arm (79.2% vs. 77.8%, P = 0.62). Interestingly, the study showed a significant increase in the pregnancy outcome of the AMA patients of PGT-A group (77.8% vs. 57.8%, P = 0.002) as compared to the non-PGT-A group. Conclusions:> The present study demonstrates that the transfer of PGT-A-selected euploid embryo significantly improves the pregnancy outcome in AMA patients.
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Is embryogenesis and ART outcome different in polycystic ovary syndrome? p. 79
Madhuri Patil, Priyanka Reddy, Chinmayie Chandrashekar, Milind Patil
DOI:10.4103/tofj.tofj_20_19  
Introduction: As oogenesis is a continuum of months, oocyte quality will be dictated by events that occur during both the growth and maturation stages of development. Morphological variation of the oocyte and embryo result from intrinsic factors such as age and genetic defects or extrinsic factors such as stimulation protocol, culture condition, and nutrition. Controlled ovarian stimulation (COH) interferes with the balance of forces within the ovary and overrides their endogenous pattern of control to optimize normal selection process. Aim: 1. To compare the embryogenesis and outcome of assisted reproductive technology (ART) in polycystic ovary syndrome (PCOS) and non-PCOS women. 2. To determine whether embryo quality, implantation rate (IR) and clinical pregnancy rate (CPR) are related to estradiol (E2) or progesterone (P4) levels on the day of human chorionic gonadotropin (hCG). Materials and Methods: This was a retrospective case–control study of 425 women at a Tertiary Care Center from January 2017 to December 2018. Of these 183 were PCOS and 242 non-PCOS matched for body mass index and age. We compared the follicle stimulating hormone, antral follicle count (AFC), anti-Mullerian hormone, thyroid-stimulating hormone, total gonadotropin utilized, total days of stimulation, estradiol (E2), and progesterone (P4) on the day of hCG trigger between both groups. Before entering the in vitro fertilization program, patients were classified into PCOS and non-PCOS depending on the AFC at the baseline scan done on day 2/3 of the menstrual cycle. We calculated the fertilization, cleavage, blastocyst formation rate, and utilization rate of the embryos from the total oocytes retrieved and fertilized in four different groups classified according to the E2 levels on the day of the hCG (≤1000, 1001–2000, 2001–3000, >3000 pg/ml) in both PCOS and non-PCOS women. We also looked at the IR and CPR in the above four groups in fresh cycle and included the frozen embryo transfer cycles to calculate the utilization rate. Statistical comparison was done using the Mann–Whitney U test. Results: There was no statistically significant difference in the fertilization rate (P = 0.803), cleavage rate was higher in PCOS group (P = 0.001) and blastocyst formation rate was higher in non-PCOS group (P < 0.001). There was no statistical difference seen in the grade of the embryos on day 3 and day 5 across the E2 groups in the PCOS women. The quality of embryos on D3 and D5 was much better in non-PCOS group with E2 levels more than 2000 pg/ml. The IR was similar in both PCOS and non-PCOS group when E2 values were <2000 pg/ml and >3000 pg/ml. The IR was higher in the PCOS group as compared to non-PCOS in women with E2 between 2000 and 3000 (P = 0.020). No difference in the CPR across the E2 groups. The utilization rate of the embryos per egg retrieved and per 2PN was statistically higher in patients with an E2 <1000 pg/ml in PCOS women. The utilization rate of the embryos per egg retrieved and per 2PN was significantly higher in non-PCOS when E2 was more than 2000 pg/ml. Conclusion: As embryogenesis and endometrial receptivity can be affected by high E2 and P4 levels it is highly recommended to closely monitor COS cycles by measuring serum E2 and P4 levels on D2 and at the time of hCG trigger. The dose of gonadotropins dose should be chosen in such a way that the number of oocytes retrieved should not be more than 10 to 12. When E2 and P4 are elevated over a threshold value, one should cryopreserve the embryo and transfer them in the subsequent cycle to decrease the incidence of ovarian hyperstimulation syndrome and improve the IR.
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CASE REPORTS Top

Tubal choriocarcinoma presenting as an ectopic pregnancy p. 87
Anita Kant, Grishma Dhanesha, Usha Gupta, Amrita Kaul, Divya Kant
DOI:10.4103/tofj.tofj_10_19  
Choriocarcinoma, a subtype of gestational trophoblastic disease, is a rare and aggressive neoplasm. It occurs due to neoplastic changes in the chorionic villi epithelium. Primary fallopian tube choriocarcinoma is extremely rare and commonly mistaken as ectopic pregnancy. We present a case of a 37-year-old female who presented with complaints of prolonged spotting per vaginum following an induced abortion. Ultrasound was suggestive of the right tubal ectopic pregnancy, and beta-human chorionic gonadotropin (BHCG) levels were remarkably high. The patient was taken for laparoscopy suspecting tubal ectopic pregnancy and right salpingectomy was done. Histopathology was suggestive choriocarcinoma of fallopian tube. Contrast enhanced CT scan of brain MRI pelvis, and chest X-ray showed no evidence of metastasis. Hence, the patient was managed with single-agent chemotherapy with injection methotrexate with leucovorin. The case highlights the importance of histopathological examination of tubal specimen in all patients presenting with tubal ectopic pregnancy and also the need to suspect a tubal choriocarcinoma in any patient presenting as ectopic pregnancy with high BHCG levels.
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