Proposed classification of adenomyosis in Infertile women to simplify management options undergoing ART.

OBJECTIVE: Adenomyosis associated with subfertility is a situation of a dilemma for the treating clinician as the treatment is highly controversial and there remains an overall lack of consensus regarding the value of conservative surgery with or without medical management to improve reproductive out-comes. Hence we proposed this classification based on mapping of the size of adenomyoma, its location, distance from the endometrial cavity, and any associated endometriosis by studying 100 women with adenomyosis undergoing IVF. METHODS: We did a prospective study over 2 years in 100 women with adenomyosis who underwent IVF. They were classified into 4 categories based on our management-based proposed classification and the pregnancy outcomes were studied in each group. RESULTS: According to our classification, 56% of women belonged to grade 1, 24% to grade 2, 8% to grade 3, and 12% to Grade 4 Adenomyosis. The Pregnancy rates were 71% in Grade 1, 66% with Medical management, and 33% with surgical management in Grade 2, Grade 3 were offered surrogacy, and 66% in Grade 4 Adenomyosis. CONCLUSIONS: Our classification is simple and allows cost-effective management based on the location and ex-tent of the disease with the help of ultrasonography.

Assessing the Impact of Uterine Artery Doppler and Low-Dose Aspirin on Fetomaternal Outcome: A Prospective Study in Low-Risk Pregnant Women in Western Part of India.

Introduction Fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH) are significant and clinically relevant complications observed in many pregnancies. Early prediction of these complications may be possible through the assessment of the umbilical artery pulsatility index (UAPI). However, its utility in routine practice for otherwise normal pregnancy needs further exploration in India. Objectives This study aimed to evaluate the potential benefits of incorporating UAPI for the timely use of low-dose aspirin in preventing FGR and PIH in a tertiary care hospital in the western part of India. Methodology A prospective study was conducted involving 64 low-risk (i.e., not having any feature of high-risk pregnancy) pregnant women selected from routine antenatal care outpatient departments over a period of two years. All women underwent uterine artery Doppler examination during the 11-13+6 weeks of pregnancy and those who had high UAPI received low-dose (150 mg) aspirin till the 35th week. The incidence of FGR and PIH was analyzed and compared between high UAPI and normal UAPI pregnancy. Results A total of 64 pregnant women with a mean age of 27.11±4 years participated in the study. Among the women, eight (12.5%) were found to have high UAPI and were put on aspirin. Among those eight women, two developed PIH. In the normal UAPI group, nine (16.07%) developed PIH (p-value = 0.62). FGR was found in one case among the eight who received aspirin and in eight cases among the 56 who had normal UAPI (p-value > 0.99). Conclusion The study concluded that despite having normal UAPI, women categorized as low-risk may develop PIH and FGR. Hence, the routine use of UAPI should be investigated in further cohort studies using a large sample to draw a generalizable conclusion for the Indian population.

Medroxyprogesterone Acetate versus Gonadotropin-Releasing Hormone Antagonist for the Prevention of Premature Luteinizing Hormone Surge in hyper-responder women undergoing controlled ovarian stimulation for IVF/ICSI Cycles.

OBJECTIVE: To compare the effect of Medroxyprogesterone acetate versus Gonadotropin releasing hormone antagonist for the prevention of premature luteinizing hormone (LH) surge in infertile hyper-responder women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) cycles. METHODS: One hundred infertile hyper-responder women who were candidate for IVF/ICSI were randomly assigned into two groups. Group 1 was given 20 mg Medroxyprogesterone acetate from day 1 of the menstrual cycle till trigger day. Group 2 was given GnRH antagonist (injection Cetrorelix 0.25 mg s/c) from the day when the leading follicle reached 14 mm until the day of trigger for the prevention of premature LH surge (flexible protocol). We measured LH serum levels on day 1, day 7 of cycle and on trigger day. The primary outcome measured was the incidence of premature LH surge. Other outcome measures were total number of mature follicles on trigger day, total number of mature oocytes retrieved and number of good quality day-3 embryos. RESULTS: There was no premature luteinizing hormone surge in both groups of our study. The mean number of follicles on trigger day, mean number of M2 oocytes retrieved and mean number of good quality day-3 embryos were comparable in both the groups, with no statistically significant difference. CONCLUSIONS: The results of this study stated that MPA can be an effective alternative to GnRH antagonist for the prevention of premature LH surge in hyper-responder women undergoing COS for IVF. It is easy to use, widely available and cost-effective. It may establish a new regimen of ovarian stimulation using MPA as an oral alternative to GnRH antagonist treatment in hyper-responders.

Successful Application of Combined Autologous Bone Marrow-Derived Stem Cells and Platelet-Rich Plasma in a Case of Severe Asherman Syndrome and Subsequent in vitro Fertilization Conception.

The application of stem cells in infertility is still experimental. Thin endometrium is an important cause of cancelled or less successful frozen embryo transfer cycles. Clinically, numerous strategies have been adopted to promote endometrial regeneration including extended oestrogen administration, low-dose aspirin, pentoxifylline, tocopherol, vaginal sildenafil citrate and intrauterine perfusion with granulocyte colony-stimulating factor. However, even with the use of these therapies, the endometrium in some patients still remains unresponsive. Latest research shows that autologous bone marrow-derived stem cells (ABMDSCs) can be used for regeneration of damaged endometrium. We present a case report of patient with thin endometrium who was successfully treated with the combined use of ABMDSCs mixed with platelet-rich plasma, leading to successful in vitro fertilization conceived pregnancy. Patient consent and due ethical clearance were taken before starting the procedure.

Combined Use of Autologous Bone Marrow-derived Stem Cells and Platelet-rich Plasma for Ovarian Rejuvenation in Poor Responders.

BACKGROUND: The management of poor responders is still a challenge in modern-assisted reproductive technology. Several researches are showing encouraging results with autologous bone marrow-derived stem cells (ABMDSCs) and platelet-rich plasma (PRP) individually. Hence, we decided to study the synergistic effect of ABMDSCs with PRP. AIMS AND OBJECTIVE: The aim of the study was to assess the safety and efficacy of intraovarian instillation of ABMDSCs combined with PRP in poor responders. DESIGN: This was an interventional pilot study. Study Period: January 2017 to January 2019. MATERIALS AND METHODS: We designed a pilot study using Patient-oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) Group 3 and 4 poor responder patients (n = 20). The study group underwent laparoscopic/transvaginal intraovarian instillation of ABMDSCs combined with PRP and the outcome was analyzed - primary outcome - antral follicular count (AFC) and mature MII oocytes and secondary outcome - Anti-Mullerian hormone (AMH) levels and number of Grade A and B embryos frozen on day 3. The Wilcoxon signed-rank test and Pearson correlation were used for the statistical analysis and P < 0.05 was considered statistically significant. RESULTS: After 6 weeks of intraovarian instillation ABMDSCs mixed with PRP, patients were reassessed for AFC and AMH and their response to subsequent controlled ovarian stimulation (COS) cycle was observed. Statistically significant improvement was seen in AFC, MII oocytes, and Grade A and Grade B embryos. AMH was also increased in some patients, but the result was not statistically significant. CONCLUSION: Our results suggest that intraovarian instillation of ABMDSCs combined with PRP is safe and it optimized the recruitment of existing dormant primordial follicles to improve oocyte yield and hence the number and quality of embryos after COS in POSEIDON Group 3 and 4 poor responders.

Role of Autologous Bone Marrow-Derived Stem Cell Therapy for Follicular Recruitment in Premature Ovarian Insufficiency: Review of Literature and a Case Report of World's First Baby with Ovarian Autologous Stem Cell Therapy in a Perimenopausal Woman of Age 45 Year.

Stem cell (SC) therapy has come up enormously, particularly for indications where not much can be done medically or surgically to improve the condition. SCs are the foundation cells for every organ, tissue, and cell in the body, and it can either reproduce into a SC or differentiate into specialized types of cells. Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. POI is characterized by menstrual disturbance (amenorrhea or oligomenorrhea) with raised gonadotropins, low anti-Mullerian hormone (AMH), and estradiol level. Autologous SCs were tried in POI to increase the follicular recruitment and avoiding the need for oocyte donation program. This review analyzes the causes, etiopathogenesis, and role of autologous bone marrow-derived SC therapy (ABMDSCT) in POI. It also highlights the recent studies and summarizes the current understanding and future directions for SCs in POI. Here, we also report the first successful birth of a baby from India, where autologous SC therapy in a 45-year-old perimenopausal single woman helped in procuring a pregnancy and delivery of a healthy 2.7 kg female baby through assisted reproduction. In the absence of SC therapy, accepting oocyte donor program or adoption would have been the only viable options for this patient for which she was not ready. This may be the world's first successful case of application of ABMDSCT in a 45-year-old female to give successful birth to a healthy baby.

Autologous Intrauterine Platelet-Rich Plasma Instillation for Suboptimal Endometrium in Frozen Embryo Transfer Cycles: A Pilot Study.

INTRODUCTION: This pilot study was to evaluate the effectiveness of intrauterine infusion of autologous platelet-rich plasma (PRP) in infertile women undergoing frozen embryo transfer cycles with suboptimal endometrium. MATERIAL AND METHODS: Intrauterine instillation of autologous PRP was done in 68 women between 22 and 40 years, over 8 months, with suboptimal endometrial growth, and patients with repeated cycle cancellations, in addition to Estradiol valerate. Frozen embryo transfer was performed when the endometrium reached an optimal pattern in terms of thickness, appearance, and vascularity. RESULTS: The mean pre-PRP endometrial thickness (ET) was 5 mm which significantly increased to 7.22 mm post-PRP. There was a significant increase in vascularity, seen by the number of vascular signals seen on Power Doppler, reaching the zones 3 and 4 of the endometrium. The positive beta Human Chorionic Gonadotropin (hCG) rate was 60.93% and the clinical pregnancy rate was 45.31%. A total of 13 women are in the second trimester, 13 are in the first trimester with a healthy intrauterine pregnancy, one patient had an ectopic gestation, three had blighted ova, two had missed abortions, and two biochemical pregnancies. CONCLUSION: This study suggests that the use of autologous PRP holds promise in the treatment of women with suboptimal ET and vascularity for embryo transfer. It would help to reduce the incidence of cycle cancellations and thus even help reduce the financial and psychological burden of repeated cancelled cycles.

Obstetric complications in women with IVF conceived pregnancies and polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is often accompanied by infertility that necessitates ovulation induction using clomiphene citrate, gonadotropins or even in vitro fertilization (IVF). These treatment methods are known to increase the incidence of multiple pregnancies as well as some negative consequences, including a rise in the risk for gestational diabetes mellitus, pre-eclampsia, etc., Furthermore, pregnancies established after IVF carry an increased risk for maternal complications. However, the increased risk of developing adverse obstetric complications has been suggested to occur independently of obesity as well as in populations without assisted reproductive techniques. Many studies have been performed to study the effect of PCOS on pregnancy and the effect of pregnancy on PCOS. The hormonal milieu that is exaggerated in PCOS women is quite well understood at the biochemical and genetic levels. The maternal and neonatal outcomes of PCOS women who have undergone in vitro fertilization-embryo transfer (IVF-ET) have not been widely studied till date. This review aims to evaluate the current evidence regarding adverse obstetric outcomes of PCOS women undergoing IVF-ET. The rationale of this review is to study whether the adverse obstetric outcomes are increased in PCOS women in general, or particularly in those PCOS women who are undergoing IVF-ET. It is also important to analyze via a literature review whether the increased adverse outcomes are due to infertility in general or PCOS per se. An attempt has been made to give evidence regarding preventive strategies for obstetric complications in PCOS women who have undergone IVF-ET.

Congenital malformations and assisted reproductive technique: Where is assisted reproductive technique taking us?

Development of ART has great benefit for millions of couples all over the world and with falling fertility rate there are a growing numbers of children born with the help of ART, it is important to investigate potential risks to these children. IVF-ICSI pregnancies are associated with higher risk for multiple gestation, preterm labor and low birth weight. It is an area of great conflict and interest that whether ART is associated with increased congenital malformations or not. So, this article reviews the data and evidences linking ART to congenital malformations.

Detorsion and conservative therapy for twisted adnexa: our experience.

OBJECTIVE: 1) To determine if detorsion of the twisted adnexa is better than traditional adnexectomy to conserve the adnexa and preserve its function. 2) To determine the feasibility of detorsion in conservation of adnexa. DESIGN: Prospective Study from September 2004 to September 2008. SETTING: Private IVF and Endoscopy Centre. PATIENTS: 22 patients with twisted adnexa (15 non-pregnant and 7 pregnant). INTERVENTION: Surgical intervention and either detorsion of adnexa or adnexectomy. MAIN OUTCOME MEASURES: Ovarian preservation and conservation of ovarian function in 77.2% cases determined by: a) Follicular development on sonography (performed for one year after adnexectomy). b) Subsequent surgery for unrelated cause showing healthy ovaries. c) controlled ovarian hyperstimulation and successful oocyte retrieval subsequently. RESULTS: We could conserve the adenexa in 77.2% cases. Laparoscopic detorsion was performed in 11/15(73.33 %) of non-pregnant women and adnexectomy done in four women 26.66%. Among the seven pregnant women, adnexa could be preserved in 6/7(85.7%) and only one woman required adnexectomy. Laparotomy was required in 2/22(9%) women both of which were in late second trimester of pregnancy. In one case (4.54%) we had recurrence of torsion. 88.23% of the women with conserved adnexa showed preservation of ovarian function. CONCLUSION: Our study showed that timely diagnosis and intervention could make the difference between ovarian loss and salvage- an outcome of great importance in population of reproductive age females. Laparoscopy with its many benefits proves to be superior to laparotomy.

Hysteroscopy in postmenopausal bleeding.

OBJECTIVES: 1) To study the etiology of postmenopausal bleeding (PMB). 2) To study the significance of hysteroscopy in evaluation of the etiopathogenic factors. 3) Correlating the diagnosis after transvaginal sonography (TVS), hysteroscopy and histopathologic diagnosis. 4) Feasibility of conservative management with hysteroscopy in PMB. DESIGN: Prospective study from January 2008 to June 2009. SETTING: Department of Obstetrics and Gynecology of Ruby Hall Clinic, Pune. PATIENTS: Sixty postmenopausal women with complaint of bleeding per vaginum. INTERVENTIONS: Clinical and sonographic evaluation, followed by diagnostic and/or therapeutic hysteroscopy and guided biopsy. Hysteroscopic images were analyzed and compared with histopathologic results. MEASUREMENTS AND MAIN RESULTS: On hysteroscopy, endometrium was classified as suggestive of normal, atrophic, endometrial hyperplasia or endometrial carcinoma. Histopathologic diagnosis is taken as a gold standard to determine the efficacy of hysteroscopy in diagnosing endometrial pathologies. The sensitivity and specificity of hysteroscopy in diagnosing endometrial pathologies was assessed. CONCLUSIONS: In women with PMB, hysteroscopy is the basic tool that allows precise diagnosis of various endouterine pathologies. The average sensitivity of hysteroscopy was 97% in our study and the specificity was 98.66%. Hence, we can conclude that it is highly accurate for evaluating endometrial pathologies. For obvious benign lesions, it also provides treatment in the same sitting, therefore avoiding an extensive, morbid, and expensive procedure like hysterectomy.