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   Table of Contents - Current issue
January-June 2020
Volume 7 | Issue 1
Page Nos. 1-131

Online since Tuesday, June 30, 2020

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Editor's view point p. 1
Kuldeep Jain
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PCOS − Have we unravelled the genetics? p. 3
Surveen Ghumman
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Adjuvant therapy in assisted reproduction treatment (ART): Current evidence and recommendations for clinical practice p. 7
Sohani Verma
There is an ever-growing list of a wide variety of pharmacological agents and interventions being implicated as adjuvant therapies alongside the core fertilization techniques—IVF or ICSI. Most of the data to support use of these adjuvant therapies are based on anecdotal, heterogeneous, and underpowered studies and associated with controversial results. Clinicians should be fully aware of the best available current evidence and patients must be informed about the experimental nature of any adjuvant therapy being offered to them, when there is no robust evidence of its safety and/or effectiveness. Any adjuvant therapy should be offered only if there is potential for cost-effective, physiological, and psychological benefit and a minimum risk of harm. Further research in the form of good quality preferably RCTs on a large number of infertile couples is required to establish true effectiveness and safety of various adjuvant therapies.
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Male infertility-evaluation and management at a glance p. 26
Navdeep K Ghuman, Pratibha Singh, Sunil Raikar
Poor semen quality contributes to the sub-fertility in 30%–50% of couples undergoing IVF. Ever-changing societal values and its stress, professional pressures, delayed parenthood and rampant obesity are fuelling an exponent increase in male infertility. Traditionally evaluation and management of male infertility relied heavily on semen analysis. The need for standardization of procedures for semen analysis leads to conception of WHO laboratory manual for the examination of human semen in 1980. It has been since revised and updated four times in light of emerging evidence. But time and again these reference values have been shown to be ineffective in reliably predicting the fertility status of men and has highlighted the fact that semen analysis needs to be complemented by a comprehensive history taking, physical examination, and relevant endocrine, genetic, and other investigations. In present scenario, role of IUI with husband/partner’s sperm for male infertility is limited except in couples with physical, ethical or moral objection to IVF/ICSI. ICSI has revolutionised the treatment of male infertility. Surgical sperm retrieval in the form of PESA, TESA and open testicular biopsy has allowed azoospermic patients the opportunity of biological paternity.
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Human immunodeficiency virus and infertility p. 37
Pinkee Saxena, Surveen Ghumman
HIV infection has nowadays become a chronic disease. Antiretroviral drug therapy has improved the life expectancy of these patients. Patients are living longer and those in reproductive group have a desire for conception. HIV infected patients may have infertility. Various treatment strategies are followed so that there is minimal or no risk of HIV transmission to the uninfected partner or their offspring. ART (assisted reproductive techniques) clinics with the necessary resources can offer services to HIV infected patients and couples who are willing to use recommended risk-reducing therapies.
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GCSF in patients with thin endometrium − subcutaneous or intrauterine? p. 43
Shilpa Singal, R.K Sharma, Nupur Ahuja
Background: Granulocyte colony stimulating factor (GCSF) has a potential role in patients with persistently thin endometrium. Usually intrauterine route is employed for administering GCSF in patients with thin endometrium and data on subcutaneous route of administration is scarce. Methods: This was a randomized case control study from july 2018 to January 2019. Fifty patients with thin endometrium were enrolled in each group. In either group, GCSF was given if endometrium was less than 7mm on day 14, maximum of 2 doses. Primary outcome measured was increase in endometrium thickness and the secondary outcome was pregnancy rate. Results: Patients in both groups had similar endometrial thickness at the time of the initial evaluation: 5.27 mm in the subcutaneous and 5.34 mm in the intrauterine group. Similar change in the endometrial thickness was observed in the two groups: 1.76 in subcutaneous group and 1.84 in intrauterine group. It was observed that 61.2% had zone 3 blood flow in subcutaneous group compared to 74.1% in the intrauterine group, the difference being not statistically significant. Pregnancy rate of 40.1% in the subcutaneous group and 47.1% in intrauterine group was observed. (P>0.50). Conclusion: We concluded that G-CSF infusion leads to an improvement in endometrium thickness and this can achieved by both intrauterine and subcutaneous route. Intrauterine route is associated with slightly better results compared to subcutaneous route, though the improvement is not statistically significant. Hence, subcutaneous route can be offered to the patient, making it a viable option for administering GCSF to improve the endometrial thickness and flow in patients with thin endometrium undergoing embryo transfer.
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A pilot study on effect of autologous platelet-rich plasma on refractory thin endometrium in frozen embryo transfer cycle p. 49
Saumya Prasad, Sudha Prasad
Background: During assisted reproductive technology (ART) treatments, one of the most common reasons for cancellation of the cycle is thin endometrium. Refractory endometrium which doesn’t respond to standard medical therapies can be the aetiology of recurrent implantation failure. Thin endometrium remains an unsolved problem in the treatment of infertile women. Autologous PRP is known to help tissue regeneration. Aims: To evaluate the effect of intrauterine infusion of platelet-rich plasma in case of thin endometrium and its impact on endometrial thickness and clinical pregnancy rate. Materials and Methods: Our study was prospective randomised controlled trial done from 1st October 2018 to 1st April 2019 at Reproductive Biology & IVF Centre, Maulana Azad Medical College, New Delhi, India. Twenty- four women undergoing frozen embryo transfer with history of thin endometrium (less than 7 mm) with normal hysteroscopic examination were enrolled. Patients with uncorrected asherman syndrome, submucosal polyp, fibroid or congenital uterine anomaly were excluded from study. From day 2 of menses Tab estradiol valerate (tablet Estrabet, Abott India) was started in a dose of 6–8 mg/day. It was increased up to 12 mg/day gradually after reviewing endometrial thickness serially. Patients with thin endometrium on day 10/11 received PRP on day 11 and repeat dose after 48 hours if endometrial thickness was less than 7 mm. Frozen embryo transfer was done in patients who achieved endometrial thickness 7 mm or more. Results: The mean pre-treatment endometrial thickness was 4.68±0.96 mm, which significantly increased to 6.65±0.52 mm, post treatment (P < 0.05). Four patients out of 24 in our study could not achieve an optimal pattern of endometrium after treatment and embryo transfer was postponed. The positive beta human chorionic gonadotropin rate was 55%, and clinical pregnancy rate was 45% among them. Conclusion: PRP was found to play an effective role in thin endometrium.
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Risk factors associated with irregular menstrual cycle among young women p. 54
Mubashir Zafar
Background: Irregular menstrual cycle is common problem among young women (15–35 years). It is the major risk factor for sexually transmitted disease. The objective of this study is to determine the risk factors associated with irregular menstrual cycle among young women of age group 18–35 years. Methodology: Cross-sectional survey and 183 participants were selected through simple random sampling from the gynecology department of tertiary care hospital. Women whose age group was 18–35 years were included and structured validated questionnaire was used. Association between risk factors with irregular menstrual cycle was determined through logistic regression analysis. Results: Mean age of study participants was 24.5 (SD +/− 1.5) years. After adjustment of covariates the statistically significant association are women who have high parity (6–9 children) (OR 2.78, CI 1.96–8.07}, past medical history (OR 1.33, CI 1.38–2.92), used addicted substance (OR 5.41, CI 1.72–16.97), user of contraceptive (OR 1.21, CI 1.65–3.10), and family history of cancer (OR 3.61, CI 2.99–5.10). Conclusion: Women who have high parity, used addicted substance, and contraceptive users are the major determinants for irregular menstrual cycles. Health education and early identification and prompt treatment are the best solution for this important public issue.
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A comparative study of semen parameters of men undergoing fertility treatment from urban population residing in Delhi/NCR region and semi-urban population from adjoining states p. 60
Sweta Gupta, Vikram Jeet Singh, Ashish Fauzdar, Ajay Srivastava, Kamlesh Sharma
Objective: To analyze the difference in semen parameters of men from urban areas of Delhi/NCR with those residing outside Delhi region. Material and Methods: A retrospective cross-sectional study was undertaken at tertiary level center located in New Delhi region between the period of August 2019 to January 2020. A total of 657 men undergoing fertility workup during their infertility treatment were included in the study with 521 (79.2%) men from Delhi/NCR region (urban) and another 136 (20.7%) men from outside Delhi region (semi-urban) with mean age of both the group was 35.6 ± 5.7 years. Results and Discussion: It was observed in both the groups that there was no statistical difference noted in mean ± SD of in semen volume (1.79 ± 0.84 vs 1.78 ± 0.83), sperm concentration (49.9 ±32.4 vs 49.8 ± 32.4), total motility (58 ± 22.5 vs 58.1 ± 22.5), progressive motility (32.3 ±13.8 vs 32.2 ± 13.8) P = 0.95 and sperm morphology (2.3 ± 2.2 vs 2.3 ± 2.2). The prevalence of male factor subfertility was higher in men residing outside Delhi as compared to men of Delhi 53.1% versus 56.6% respectively and overall combined male factor in study population including the men from both the group was 58%. Conclusion: There were no significant differences in semen parameters including sperm concentration, total motility progressive motility, total motile concentration and sperm gross morphology in the men residing in urban area of Delhi and those residing in semi-urban area outside Delhi/NCR for up to three years period.
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Effect of autologous platelet-rich plasma on clinical outcome in patients with suboptimal endometrium in fresh ICSI/FET cycle − an interventional prospective study p. 70
Jyoti Gupta, Bharti Jain, Kuldeep Jain
Context: Endometrial receptivity (ER) is crucial for implantation rate and clinical pregnancy rate in ET-IVF. Endometrial receptivity is affected independently by endometrial thickness, vascularity and pattern. Aims: To evaluate the efficacy of autologous platelet-rich plasma in improving the endometrial parameters in patients with suboptimal endometrium in fresh ICSI/FET cycle. To evaluate pregnancy outcome in FET/ICSI cycles after intrauterine instillation of PRP. Settings and Design: Interventional prospective study conducted in tertiary infertility centre. Methods and Material: 30 patients with suboptimal endometrium undergoing IVF-ICSI/FET cycle with failed implantation/history of previous cycle cancellations/intrauterine adhesions on hysteroscopy were included. Patients with poor embryo quality, Bleeding dyscracias, Low platelet counts or active infections were excluded. All patients with any compromised endometrial parameter were offered intra-uterine PRP infusion. Statistical analysis used: Categorical data were presented as frequency and percentage; for comparison Chi square and McNemar tests were used wherever applicable for calculation of P-value. P-value < 0.05 was considered significant. Results: Endometrial thickness showed good response to PRP therapy and the mean increase in endometrial thickness was 1.33mm. PRP therapy significantly changed the endometrial pattern from Type A to Type B in more than half the patients (P-value = 0.001). PRP was instrumental in improving the sub-endometrial flow (22/30 patients, 73.3%) and uterine artery resistance (16/20, 80%), more so in subgroup of patients suffering from Intrauterine adhesions (P-value = 0.004 and 0.001 respectively). 43.3% (13/30) showed positive β-hCG. A clinical pregnancy rate of 30% (9/30) was seen. Conclusions: PRP has promising results in patients with suboptimal endometrium by increasing endometrial thickness, ameliorating pattern and improving vascularity with reduced cancellation rate.
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To assess serum Anti Mullerian Hormone (AMH) level as a biomarker for oocyte quality p. 78
Aneesha M Grover, Sonia Malik, Ved Prakash, Vandana Bhatia
Introduction: Oocyte competence is a factor that affects ART outcomes. Oocyte morphology assessment and scoring are laborious, have inter-observer variations and lack consensus on parameters to be assessed. Role of anti mullerian hormone (AMH) as a biomarker for oocyte quality and competence is investigated. Aim and Objectives: To evaluate day 2/3 serum AMH as a predictor of oocyte quality, embryo quality and fertilization rate in a stimulated ART cycle. Methods: Single centre, prospective observational study. All patients undergoing IVF-ICSI between August 2018 and February 2019 included. Total Oocyte Score calculated for all oocytes. and subsequently assessed for fertilization, cleavage and day 3 embryo grading. Correlations between AMH levels and TOS, PTOS, Fertilization and Cleavage rates assessed using appropriate statistical methods. Results: Of 86 patients and 780 oocytes studied,639 underwent ICSI with fertilization rate 86% (550/639) and cleavage rate 90.7%(499/550). Embryo grades were A-50.6%, B-38.9% and C-10.5%. Mean TOS score and PTOS scores were 0.3±1.99 and 0.44±1.21.TOS was predictive of fertilization [ROC-AUC=0.598(P = 0.004)]. Mean AMH levels were 3.66 ± 3.96 ng/ml [0.69±0.21ng/ml<25th centile, 2.74±1.14 ng/ml, 25th–75th centile, 8.27±5.08ng/ml>75th centile] and decreased with increasing age. AMH levels correlated with TOS, PTOS, fertilization and cleavage rates. The r2 values were low suggesting poor clinical significance. AMH levels were not predictive of fertilization and embryo grade. Conclusion: AMH levels show weak correlation with oocyte quality and are poor predictor of oocyte competence.
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Role of daily ejaculation for four consecutive days in improving sperm DNA fragmentation index p. 85
Balpreet Kaur, Ved Prakash, Sonia Malik, Vandana Bhatia, Aneesha Grover, Deepu Gupta
Introduction: Semen analysis is the gold standard for determining male partner fertility but it does not provide any information about the genetic make-up of the sperm, which is essential for normal embryo development. High sperm DNA fragmentation is also found in men with normal semen parameters. Sperm with high DNA damage leads to nuclear instability in the embryo, resulting in developmental arrest, implantation failure, higher miscarriage rate, genetic mutations causing abnormalities in the offspring and increased susceptibility to childhood cancers. European Society for Human Reproduction and Embryology (ESHRE 2017) guidelines recommend sperm DNA fragmentation testing for men whose partners experience recurrent pregnancy loss. In 25th annual meeting of ESHRE it was discussed that daily sex helps to reduce sperm DNA damage and improve fertility. The basis for this is that daily ejaculations reduce the exposure of sperms to reactive oxygen species in testicular ducts and epididymis; hence less DNA damage and improvement in DNA fragmentation index. Extrapolating this, it is hypothesized that a reduction in DFI will be observed when analysing semen obtained after daily ejaculation for four days. Aim: The aim of the study is to evaluate the role of daily ejaculation for four consecutive days in improving the sperm DNA fragmentation index (DFI). Materials and Methods: Out of 170 semen samples, 65 patients had DFI of > 30% in a routine workup of male factor in an infertile couple and were recruited. Of these 56 opted for participating in this study. The initial semen sample was collected after an abstinence of 2-3 days. These patients were then asked to ejaculate daily for four consecutive days. During this period, no medication or any lifestyle modification was advised to these patients. Repeat semen sample was then collected on fifth day and DNA fragmentation index was calculated using the sperm chromatin dispersion (SCD) test. Results: The mean age of the patients was 35.52 years (range 29–50 years). The Indications for raised DFI were: age > 35 years (41%), BMI >25 (30.35%), defective spermatogenesis (31%), diabetes (5.35%), varicocoele (5.35%), smoking (32.14%). The mean DFI in the initial sample was 57.36 ± 17.54 and the mean DFI in the repeat sample was 32.33 ± 21.62. The reduction in the DFI was statistically significant with a P-value of <0.0001. A decrease in the sperm count after daily ejaculations was also observed but the difference was not statistically significant (45.05 ± 31.47 vs 41.38 ± 33.72; P-value = 0.07). No statistically significant difference was seen in the sperm motility (45.59 ± 15.47 vs 46.5 ± 14.33) and sperm morphology (11.11 ± 13.17 vs 10.75 ± 12.94) after repeated ejaculations. Conclusion: Daily ejaculations for four consecutive days by patients showing high sperm DNA damage is a cost-effective method of reducing DFI without compromising other semen parameters.
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Variation of post trigger LH, progesterone and HCG levels with BMI and its impact on recovery rates of oocytes during IVF/ICSI cycles p. 92
Mohita Gupta, Surveen Ghumman, Shalini Chawla Khanna, Sandesh Patel
Aims and Objectives: To assess the variation in post trigger LH, progesterone and HCG levels with BMI after agonist/HCG trigger during ART cycles and its impact on recovery rate of oocytes. Material and Methods: A prospective study was conducted at Max Multispeciality Hospital Panchsheel Park, New Delhi from May 2018 – Feb 2019. A total of 101 patients (51 in agonist trigger and 50 in HCG trigger group) met the inclusion and exclusion criteria, were enrolled after taking written consent. Agonist trigger patients received either decapepty l0.3 mg or lupride 3 mg trigger. HCG trigger group received ovitrelle 500 mcg. Trigger day and 10–12 hours post trigger LH, progesterone and HCG was done and its correlation to BMI and recovery rates was analyzed. P value <0.05 was considered significant. Results: BMI showed significant negative correlation with post trigger LH levels (P=0.047), LH rise (P=0.036) in group 1 and post trigger HCG levels in group 2 (P=0.026) levels. When BMI was categorized into 4 groups, in group 1, post trigger progesterone showed decreasing trend with increasing BMI (P=0.05) with comparable recovery rates but in group 2, post trigger HCG, progesterone levels and recovery rates were found to drop as BMI increased >30 kg/m2. Conclusion: BMI should be considered while deciding dose of the trigger keeping in mind the variation of Post trigger LH, progesterone and HCG levels with BMI. Further large randomized controlled trails are required to validate the results found in this study.
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Pains of the bane of infertile women in Southwest Nigeria: a qualitative approach p. 99
Lateef Olutoyin Oluwole, Adetunji Obadeji, Mobolaji U Dada
Context: Infertility can be painful as it affects every aspect of life and relationship. In traditional African societies children are of great socioeconomic value. The invisible grieving of women living with infertility is enormous, and exposes such women to sundry psychological burden. Aims: This study qualitatively explored the viewpoints, and the psychological burden of women living with infertility in southwest Nigeria. Settings and Design: This study adopted a qualitative approach to investigate the experience of women who were undergoing treatment for infertility at a tertiary health facility in southwest Nigeria. Methods and Material: A qualitative approach was adopted for profound exploration with a view to appraising their holistic subjective experiences of infertility. Statistical analysis: Data for analysis was obtained through verbatim transcription of interview as recorded by audio recorder and note taking. Systematic text condensation was used to analyze the data. Results: Majority of the participants who were in monogamous relationship were religious and lived with their spouses. A total of 43 significant statements were discerned and sorted into 8 themes including isolation, anxiety, shame, low self-esteem, anger cum resentment, and hopelessness. Conclusions: It would require a multi-disciplinary approach to relieve the pains, and alleviate the baneful experience of infertile couples.
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Role of pre IVF hysteroscopy in women with unexplained infertility for detecting unsuspected intrauterine lesions and effect on pregnancy outcome p. 105
Shipra Singla, Sweta Gupta, Rachita Munjal, Sonia Chawla, Biswa Bhusan Dash
Objective: The relevance of routine hysteroscopy before IVF is debatable and there is no consensus on the effectiveness of routine pre IVF hysteroscopy in improving pregnancy outcome. The purpose of this study is to assess the role of pre IVF hysteroscopy in women with unexplained infertility in detecting unsuspected intrauterine lesions and its effect on pregnancy outcome. Materials and Methods: This was retrospective observational study conducted at Medicover Fertility Center, New Delhi, India. In the study group (n = 60), women with unexplained infertility of more than three years with normal transvaginal ultrasonography were included, where hysteroscopy was done in post-menstrual period, 1–2 months before starting IVF treatment. In the control group (n = 60), pre IVF hysteroscopy was not done. Results: The study and control group did not differ for age, body mass index, duration and type of infertility. There was a high prevalence (31.6%) of unsuspected intrauterine abnormalities in women with unexplained infertility with normal transvaginal ultrasound findings. The clinical pregnancy rate was 48.3% (29/60) in study group and 36.7% (22/60) in control group. The clinical pregnancy rate (CPR) was observationally higher in women with pre IVF hysteroscopy, but the difference was not statistically significant (P value = 0.193). Conclusion: There was high prevalence rate of unsuspected intrauterine lesions in women with unexplained infertility. Clinical pregnancy rates were not significantly higher in patients who underwent pre IVF hysteroscopy. Further larger studies and randomized controlled trials are needed to verify the positive outcome of use of hysteroscopy prior to IVF.
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Alteration of neutral-alpha glucosidase in seminal plasma and correlation with sperm motility among men investigated for infertility Nigeria: a cross-sectional study p. 111
Muyiwa Adeleye Moronkeji, Mathias Abiodun Emokpae
Introduction: Proteomic studies are becoming popular lately among reproductive biologists in the diagnosis and management of several diseases including male infertility. Objective: To evaluate the level of Neutral-alpha Glucosidase (NAG) in the seminal plasma of men being investigated for infertility in and to correlate its activity with sperm motility. Materials and Methods: Four hundred men age range 23–60 years were consecutively recruited in the study. After physical and clinical evaluation, the semen was collected by self or assisted masturbation and analysis was done according to the World Health Organization guidelines. The semen was then centrifuged and seminal plasma separated for the assay of NAG activity by ELISA technique using reagents supplied by Melson Medical Co, Shangai, China within one week of collection. The participants were categorized in to normozoospermia (191), oligozoospermia (98), severe oligozoospermia (70) and azoospermia (41) based on sperm count. Results: The mean levels of NAG activity decreased with decreasing levels of sperm count with values lowest among azoospermia and highest among normozoospermic subjects. The comparison of NAG activity between the various categories and control subjects was significantly different (P<0.001) except for normozoospermia which was not significantly different (P>0.05) when compared with controls. The mean NAG activity level was significantly lower among the asthenozoospermia (P<0.001) compared with normozoospermia. The NAG activity correlated positively with percentage sperm motility (r=0.126; P<0.02) and percentage sperm count (r=0.107; P<0.05). Conclusion: The findings indicate that NAG can be used for the assessment of semen quality as an adjunct to traditional semen analysis.
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A rare incidental case of an accessory fallopian tube p. 117
Sonam Sharma
Developmental anomalies of the müllerian duct system represent one of the most fascinating disorders that obstetricians and gynecologists encounter as the müllerian ducts are the primordial anlage of the female reproductive tract. Accessory fallopian tube is one such rare anatomical müllerian duct error that has been occasionally reported in the literature. Due to the limited data available and lack of awareness about this entity, it is often overlooked. This report describes one such rare incidental case of an accessory fallopian tube in a 35-year-old female who was diagnosed with right ruptured tubal pregnancy. The patient was about six weeks pregnant and presented with a severe lower abdominal pain. Transvaginal sonography showed that the right fallopian tube contained a gestational sac with a yolk sac and her urine pregnancy test was positive, so a diagnosis of a right ruptured tubal pregnancy was made. Laparotomy and right salpingectomy were performed. Histopathological examination revealed right ruptured tubal pregnancy with a coexisting accessory fallopian tube. In conclusion, an early identification and prompt intervention are paramount for treating such an anomaly as it can have many gynecological detrimental implications.
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Delayed interval delivery (DID) with raised markers of infection and emergency cervical cerclage − a case report and review of literature p. 121
Rashmi Sharma, Ranu Dadu
Typically, all fetuses of a multiple gestations deliver within a short interval; however, in selected cases, the preterm birth of one fetus may not require delivery of the other fetus (es). An extended time interval between births of siblings at a critical gestational age may improve neonatal survival and reduce morbidity from preterm birth. We report a case of 41year old woman with twin IVF pregnancy, in which the first twin delivered at 22 weeks and the second twin was delivered at 31 weeks with a favourable outcome. Conclusion: With the increasing use of ART and consequent multifetal gestation, premature delivery is the most dreaded complication with the loss of all babies. In recent years the approach to the fate of after coming twins during preterm delivery has changed. Desperate attempts to salvage the second twin by delaying delivery have been reported recently in some cases with favourable outcome for the second twin.
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Joint IFS-ISAR-ACE Recommendations on Resuming/Opening up Assisted Reproductive Technology Services p. 125
Sudha Prasad, Prakash Trivedi, Neena Malhotra, Madhuri Patil, Dakshinamoorthy Swaminathan, Sanjay Shukla, Kedar Ganla
COVID-19–A Global challenge on a scale not previously seen. Reproductive care is essential for the well-being of society and therefore the treatment needs to be completely re-thought and individualised . Infectivity and mortality rates are higher than previous pandemics and the disease is present in almost every country. Propagation and containment have varied widely by location and, at present, the timeline to complete resolution is unknown. With successful mitigation strategies in some areas and emergence of additional data, the societies have sanctioned gradual and judicious resumption of delivery of full reproductive care. When we resume, monitor local conditions, including prevalence of disease, status of government or state regulations, and availability of resource. It is important to implement proactive risk assessment within their practices prior to restarting services. One needs to develop clear and modified plans to ensure the ability to provide care while maximizing the safety of their patients and staff. One should also remain informed and stay current regarding new medical findings. These recommendations provide resources for restarting ART practice again.
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