Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.

The leading indicator for successful outcomes in in-vitro fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.

The role of probiotics in improving menstrual health in women with primary dysmenorrhoea: A randomized, double-blind, placebo-controlled trial (the PERIOD study).

BACKGROUND: Primary dysmenorrhea is associated with poorer quality of life; however, the causal mechanism remains unclear. A vast body of literature supports the use of oral probiotics for relief from the symptoms of endometriosis; however, to our knowledge, no study has prescribed probiotics for primary dysmenorrhea. OBJECTIVE: The aim of this study is to investigate the effects of 3-month supplementation with oral probiotics on quality of life and inflammatory markers in women with primary dysmenorrhea. DESIGN: Randomized placebo-controlled trial. METHODS: A total of 72 patients (36 patients in each arm) were randomized to receive either oral sachets containing 5 billion colony-forming units each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 each or placebo twice daily for 3 months. Main outcome measures were visual analog scale, verbal rating scale, physical and mental health scores using Short-Form 12-Item version 2 questionnaire, frequency of nonsteroidal anti-inflammatory drug use, and changes in inflammatory markers (interleukin-6, interleukin-8, and tumor necrosis factor alpha) before and after treatment. RESULTS: There was no significant difference in the quality of life scores between the probiotic and placebo groups. Both groups showed significant improvement in pain (visual analog scale) and severity (verbal rating scale) scores but the probiotic group had much lower nonsteroidal anti-inflammatory drug use (odds ratio: 0.69, 95% confidence interval: 0.26-1.83) and better mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) than the placebo group. There was a significant confounding effect of nonsteroidal anti-inflammatory drug use on quality of life scores. No significant difference was found in inflammatory cytokines. CONCLUSION: Tested oral probiotics improved mental health and potentially reduced the use of nonsteroidal anti-inflammatory drugs; however, there was no significant change in inflammatory markers. Further research with a larger sample size is needed to confirm the findings. REGISTRATION: This study is registered under ClinicalTrials.gov (NCT04119011).

Use of Probiotic in Primary DysmenorrhoeaThis study looked at whether taking probiotics (good bacteria) for 3 months could improve the quality of life and reduce pain in women with painful periods. The study found that probiotics did not significantly improve quality of life scores, but did reduce the use of painkillers and improve mental health scores. However, the probiotics did not have a significant effect on inflammatory markers in the body. More research is needed to confirm the findings.

Unexplained subfertility: active or conservative management?

OBJECTIVES: Unexplained subfertility (UEI) describes a couple whose standard subfertility workout consider acceptable but unable to conceived. METHODS: This retrospective study was conducted in the Advanced Reproductive Centre, UKM Hospital, Kuala Lumpur, from January 2016 to December 2019. The data of 268 UEI couples were obtained from the clinical database. Women aged 21-45 years old was included and further divided into four groups according to the female partner's age and subfertility duration: group A (age <35 years and subfertility <2 years), group B (age <35 years and subfertility >2 years), group C (age >35 years and subfertility <2 years), and group D (age >35 years and subfertility <2 years). All statistical analyses were performed using SPSS 22.0 for Windows. RESULTS: A total of 255 cases were included in this study. The mean age of the women was 32.9 ± 4.04 years, and the mean subfertility duration was 5.04 ± 2.9 years. A total of 51 (20 %) cases underwent timed sexual intercourse, 147 (57.6 %) cases had intrauterine insemination (IUI), whereas 57 (22.4 %) cases opted for in vitro fertilization (IVF). A total of 204 cases underwent active management (IUI/IVF), which showed a significant difference (p<0.05). Out of eight clinical pregnancies, half of them were from group B. CONCLUSIONS: Active management in younger women with a shorter subfertility duration revealed a better pregnancy outcome. Otherwise, individualized treatment should be considered in selecting a suitable treatment plan.

Infertility and cortisol: a systematic review.

Introduction: Stress and infertility form a complex relationship. In line with this, various stress-related biological markers have been investigated in infertility. Methods: This systematic review was performed using PRISMA guidelines (i) to report whether cortisol is highly present in infertile patients compared to fertile control; (ii) to report whether there is any significant difference in the cortisol level in infertile subjects that conceive and those that didn't at the end of assisted reproduction treatments. Original articles involving human (male and female) as subjects were extracted from four electronic databases, including the list of references from the published papers. Sixteen original full-length articles involving male (4), female (11), and both genders (1) were included. Results: Findings from studies that compared the cortisol level between infertile and fertile subjects indicate that (i) Male: three studies reported elevated cortisol level in infertile patients and one found no significant difference; (ii) Female: four studies reported increased cortisol level in infertile subjects and three studies found no significant difference. Findings from studies that measured the cortisol level from infertile patients that conceived and those that didn't indicate that (i) Male: one study reported no significant difference; (ii) Female: one study reported elevated cortisol in infertile patients that conceived, whereas two studies reported increased cortisol in infertile patients that was unable to conceive. Five studies found no significant difference between the groups. Discussion: In the present review we only included the cortisol value that was measured prior to stimulation or IVF treatment or during natural or spontaneous cycles, despite this, there are still variations in the sampling period, assessment techniques and patients' characteristics. Hence, at present, we are still unable to conclude that cortisol is significantly elevated in infertile patients. We warrant future studies to standardize the time of biological sample collection and other limitations that were addressed in the review to negate the unwanted influencing factors.

The spectrum of in vitro maturation in clinical practice: the current insight.

In vitro oocyte maturation (IVM) has been used worldwide. Despite the long-term implementation, the uptake of this procedure to complement current in vitro fertilization (IVF) remains low. The main reason is likely due to the non-synchronization of protocol and definition criteria, leading to difficulty in collective proper outcome data worldwide and, thus, lack of understanding of the exact IVM procedure. The review aims to consolidate the current clinical practice of IVM by dissecting relevant publications to be tailored for a current spectrum of clinical practice. Nevertheless, the background theories of oocyte maturation were also explored to provide a comprehensive understanding of the basis of IVM theories. Additional discussion of other potential uses of IVM in the future, such as in ovarian tissue cryopreservation known as OTO-IVM for fertility preservation and among women with diminished ovarian reserve, was also explored. Otherwise, future collaboration among all IVM centers is paramount for better collection of clinical data to provide valid recommendations for IVM in clinical practice, especially in molecular integrity and possible DNA alteration if present for IVM offspring outcome safety purposes.

Effects of Dehydroepiandrosterone (DHEA) Supplementation on Ovarian Cumulus Cells following In Vitro Fertilization (IVF)/Intra-Cytoplasmic Sperm Injection (ICSI) Treatment-A Systematic Review.

Despite many studies exploring the effects of DHEA supplementation, its application in IVF procedure continues to be a subject of debate owing to the inconsistent findings and the lack of rigorously designed, large-scale, randomized trials. Our review aims to explore the effectiveness of DHEA supplementation in ovarian cumulus cells following IVF/ICSI treatment. We conducted a literature search of Pub-Med, Ovid MEDLINE, and SCOPUS (inception to June 2022) for all relevant articles, including the keywords of "dehydroepiandrosterone/DHEA", "oocyte", and "cumulus cells". From the preliminary search, 69 publications were identified, and following a thorough screening process, seven studies were ultimately incorporated into the final review. Four hundred twenty-four women were enrolled in these studies, with DHEA supplementation being administered exclusively to women exhibiting poor ovarian response/diminished ovarian reserve or belonging to an older age demographic. The intervention in the studies was DHEA 75-90 mg daily for at least 8-12 weeks. The only randomized controlled trial showed no difference in clinical or cumulus cell-related outcomes between the control and treatment groups. However, the remaining six studies (two cohorts, four case-controls) showed significant beneficial effects of DHEA in cumulus cell-related outcomes compared to the group (older age or POR/DOR) without DHEA supplementation. All studies revealed no significant difference in stimulation and pregnancy outcomes. Our review concludes that DHEA supplementation did show beneficial effect on ovarian cumulus cells in improving oocyte quality for women of advanced age or with poor ovarian responders.

Endometrial Heparin-Binding Epidermal Growth Factor Gene Expression and Hormone Level Changes in Implantation Window of Obese Women with Polycystic Ovarian Syndrome.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder amongst reproductive-age women, and 61% to 76% of women with PCOS are obese. Obese women with PCOS are usually burdened with infertility problems due to implantation failure. Thus, progesterone treatment is usually used to improve implantation rates. Although Hb-EGF expression is actively involved in endometrial receptivity and implantation, the data on heparin-binding epidermal growth factor (Hb-EGF) expression following progesterone therapy in obese women with PCOS are still lacking. OBJECTIVE: To investigate the changes in serum follicle-stimulating hormone (FSH), luteinising hormone (LH), dehydroepiandrosterone sulphate (DHEA), progesterone and oestradiol levels and Hb-EGF expression in obese women with PCOS during the implantation window following progesterone therapy. METHOD: A total of 40 participants aged 18-40 years old were recruited following the provision of written consent. The participants were divided into the obese PCOS, normal-weight PCOS, obese fertile and normal-weight fertile groups. First blood collection was done before ovulation. Then, daily oral micronised progesterone (Utrogestan 200 mg) was given to the PCOS group for 10 days. The treatment was followed by a second blood collection and endometrial tissue sampling by using a Pipelle de Cornier catheter. In the fertile group, ovulation was confirmed by using ultrasound, and a second blood sample was collected on days 7 to 9 postovulation. The serum levels of FSH, LH, DHEA, progesterone and oestradiol were measured in all participants. Wilcoxon signed-rank test was used to compare FSH, LH, DHEA, progesterone and oestradiol levels during pre- and postovulation. Mann-Whitney test was performed to compare FSH, LH, DHEA, progesterone and oestradiol levels between two groups: (1) the PCOS group and the fertile group, (2) the obese PCOS group and the non-obese PCOS group and (3) the obese group and the non-obese fertile group. RESULT: Serum FSH levels were lower in obese women in their follicular phase than in women with normal weight regardless of their PCOS status, whereas serum LH/FSH ratios and DHEA levels were higher in women with PCOS than in women without PCOS. However, endometrial Hb-EGF expression was lower in the obese PCOS group than in the normal-weight PCOS group. CONCLUSIONS: Different patterns of hormonal levels and Hb-EGF expression levels were seen between the studied groups. However, further in vitro and in vivo studies are needed to investigate the mechanism underlying the changes in FSH, LH/FSH ratio, DHEA and Hb-EGF expression in PCOS after progesterone treatment.

Probiotics, a promising therapy to reduce the recurrence of bacterial vaginosis in women? a systematic review and meta-analysis of randomized controlled trials.

Introduction: The evidence for probiotic efficacy in preventing bacterial vaginosis (BV) recurrences among women aged 18 years and above is sparse. We aimed to ascertain the efficacy of probiotics in preventing BV recurrences after at least one menstrual cycle in this population. Methods: We conducted a systematic literature search using PubMed, MEDLINE (Ovid interface), Web of Science (WoS), Scopus, Embase, ProQuest Dissertations and Theses Global, Cochrane Library databases and registries comprised of Open Science Framework (OSF) preprints registry, the ClinicalTrials.gov (USA), WHO International Clinical Trials Registry Platform (WHO-ICTRP), International Standard RCT Number (ISRCTN) registry, limited to randomized clinical trials (RCTs) in English published between January 2000 and December 2021. The inclusion criteria were trials that administered probiotics to BV-positive women in an experimental arm of at least 20 samples. The usage of probiotics should be preceded with standard antibiotic regimen and followed by a reassessment of BV status after at least a single menstrual cycle. Risk of bias assessment was completed using revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The PROSPERO registration number of the review is CRD42022302044. Results: From 8,162 identified records, we included 10 studies (n = 1,234 participants) for final analysis; 7 trials compared probiotics vs. placebo, whereas 3 trials compared probiotics vs. metronidazole alone. Using random-effects meta-analysis, probiotics were shown to reduce the risk of BV recurrences by 45% compared to either placebo or metronidazole [14.8 vs. 25.5%, RR: 0.55 (95%CI: 0.33, 0.91), p = 0.03, I 2 = 45.4% (95%CI: 0, 73.7%)]. Sensitivity analysis revealed the robustness of results upon removal of studies with high risk of bias [RR: 0.54 (95%CI: 0.38, 0.77), p = 0.006] and reporting bias (RR: 0.53, 95%CI: 0.39, 0.74, p = 0.002). Meta-regression demonstrated that the route of administration (p vaginal = 0.67; p oral = 0.44), the total dosage of probiotics (p = 0.17), cumulative days of probiotic administration (p = 0.76), and the number of species in probiotic preparation (p = 0.40) were not linked to BV recurrences. Interpretation: Probiotics were associated with more than twofold reduction in BV recurrences when BV status was assessed after at least 1-month postintervention. Further high-quality and methodologically standardized RCTs should evaluate probiotic efficacy for BV prevention in a diverse community setting. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290613], identifier [CRD42021290613].

Comparison of Treatment Outcomes among Sibling Oocytes Using Different Culture Systems-Conventional IVF versus INVOcell Device-And Evaluation of INVOcell User Satisfaction: The INVOcIVF Study.

INVOcell is considered an alternative to conventional IVF proposed for intravaginal embryo culture; however, implementation is still low because evidence is scanty regarding its outcome and, most importantly, the device's user satisfaction. Thus, we aim to compare the embryo outcome of sibling oocytes following INVOcell culture with conventional IVF (cIVF) by assessing its clinical outcome (fertilization, blastulation rate, and good embryo quality) and the user satisfaction evaluation based on a local validation questionnaire. A prospective study was done at a university-setting hospital for 12 months (July 2021-2022). The oocytes collected were divided into INVOcell and cIVF groups equally. Inclusion criteria included <40 years old and body mass index (BMI) < 30 kg/m2. The pre- and post-satisfaction questionnaires were assessed. In total, 23 women were included following standard controlled ovarian stimulation (COS). The mean age was 32.9, and the mean BMI was 24.9 kg/m2. Most of them suffered from tubal factors. A total of 252 oocytes were collected and incubated accordingly (cIVF; 138, INVOcell; 114). The blastulation rate was superior in the INVOcell group (p = 0.16); otherwise, the fertilization rate and good embryo quality were not significantly different between both methods (p > 0.05). Overall, women were satisfied with the INVOcell device as they were adequately advised, follow-up was scheduled, and the lowest score was obtained for all side effects of the device. Although both methods produce similar fertilization rates and good-quality embryos, the blastulation rates were better in the INVOcell group. Functionally, it is a user-friendly device and tolerable. Therefore, INVOcell can be used as an alternative method for reproductive treatment in carefully selected patients without jeopardizing the IVF outcomes.

Safety and effectiveness of fondaparinux as a postpartum thromboprophylaxis during puerperium among muslim women: A single centre prospective study.

Background: Venous thromboembolism (VTE) remains one of the leading causes of maternal morbidity and mortality, with postpartum period carrying the greatest risk. Perinatal thromboprophylaxis is often administered based on risk-factor assessment. Low molecular weight heparin has a proven safety profile in the obstetrics population, however, its porcine-derived content may lead to reduced uptake amongst certain religious groups. We aimed to evaluate the safety of fondaparinux as an alternative postpartum thromboprophylaxis. Methods: We conducted a prospective, single arm, open label study from September 2017 until March 2018. Women who fulfilled the criteria for post natal thromboprophylaxis based on the 2015 RCOG guidelines were recruited. Each patient received subcutaneous injection of Fondaparinux, 2.5 mg daily for 10 days. A telephone interview was conducted on day 10 post delivery. Each woman was subsequently reviewed in the outpatient clinic 6 weeks postpartum. The primary outcome measure was occurrence of pulmonary embolism or deep vein thrombosis suggestive by clinical symptoms and assessment. Secondary outcome measures were allergic reaction and bleeding tendency such as secondary post-partum haemorrhage, spinal site bleeding and wound haematoma. Allergic reaction and bleeding tendency in neonates were also recorded. Results: Sixty women were included in the analysis. There were no VTE cases amongst our cohort. No major bleeding was recorded. Two patients (3.3%) had wound haematoma, one of which occurred 3 weeks post delivery. No adverse effect in neonates was noted. Conclusion: Fondaparinux is a safe alternative thromboprophylaxis for postpartum women.

Effect of Acupressure at P6 on Nausea and Vomiting in Women with Hyperemesis Gravidarum: A Randomized Controlled Trial.

Hyperemesis gravidarum is characterized by severe nausea and vomiting. This study aims to illustrate the efficacy of acupressure at P6 in treating nausea and vomiting in hyperemesis gravidarum. This parallel randomized controlled trial was conducted from 2016-2017 in a tertiary hospital. Hospitalized women with ≤16 weeks of gestation and moderate to severe nausea and vomiting classified using a modified PUQE score were randomly assigned in a 1:1 ratio to either apply an acupressure wristband at the P6 point three times daily or to receive regular doses of intravenous antiemetics. The primary outcome was differences in modified PUQE scores among the groups. The secondary outcomes were differences in the rate of urine ketone clearance and the frequency of requiring rescue antiemetics. Ninety women were equally randomized into two groups, with no dropout. There was a statistically significant difference in the degrees of nausea and vomiting between the groups at 8, 16, and 24 hours post-admission (p8hours= 0.001, p16hours = 0.006, and p24hours = 0.001). The requirement of antiemetics and the rate of urine ketone clearance between the two groups were also statistically significant, at p = 0.001 and p = 0.02 respectively. There were no side effects in either group. The P6 acupressure was efficacious in alleviating nausea and vomiting among hyperemesis gravidarum women. The trial was retrospectively registered on ClinicalTrials.gov (NCT05175079).

Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials.

Polycystic ovary syndrome (PCOS) and endometriosis are reproductive disorders that may cause infertility. The pathology of both diseases has been suggested to be associated with sex steroid hormone receptors, including oestrogen receptors (ER), progesterone receptors (PRs) and androgen receptors (ARs). Therefore, with this review, we aim to provide an update on the available knowledge of these receptors and how their interactions contribute to the pathogenesis of PCOS and endometriosis. One of the main PCOS-related medical conditions is abnormal folliculogenesis, which is associated with the downregulation of ER and AR expression in the ovaries. In addition, metabolic disorders in PCOS are caused by dysregulation of sex steroid hormone receptor expression. Furthermore, endometriosis is related to the upregulation of ER and the downregulation of PR expression. These receptors may serve as therapeutic targets for the treatment of PCOS-related disorders and endometriosis, considering their pathophysiological roles. Receptor agonists may be applied to increase the expression of a specific receptor and treat endometriosis or metabolic disorders. In contrast, receptor antagonist functions to reduce receptor expression and can be used to treat endometriosis and induce ovulation. Understanding PCOS and the pathological roles of endometriosis sex steroid receptors is crucial for developing potential therapeutic strategies to treat infertility in both conditions. Therefore, research should be continued to fill the knowledge gap regarding the subject.

A Systematic Review and Integrated Bioinformatic Analysis of Candidate Genes and Pathways in the Endometrium of Patients With Polycystic Ovary Syndrome During the Implantation Window.

Polycystic ovary syndrome (PCOS) is a common disorder with wide-ranging clinical heterogeneity that causes infertility. However, the comprehensive molecular mechanisms of PCOS in causing infertility is remaining unclear. Hence, a comprehensive literature search was conducted using PubMed, Scopus, EBSCOhost, and Science Direct. Medical Subject Heading (MeSH) terms like PCOS, gene expression, implantation window and endometrium were used as the keywords. From 138 studies retrieved, original articles with RNA profiling on human endometrial tissues in PCOS women during the implantation window were included. Study design, sample size, sample type, method, and differentially expressed genes (DEGs) were identified from all publications. The DEGs were analyzed using the software packages DAVID, STRING, and Cytoscape. Three studies that met inclusion criteria were included, and 368 DEGs were identified. Twelve significant clusters from the protein-protein interaction network (PPI) complex were found, and cluster 1 showed very high intermolecular interactions. Five candidate genes (AURKA, CDC25C, KIF23, KIF2C, and NDC80) were identified from the systematic review and integrated bioinformatics analysis. It is concluded that cell cycle is the fundamental biological processes that were dysregulated in the endometrium of PCOS women, affecting decidualization progression in the endometrium during the implantation window.

The Reliability and Validity of the Malay Version of Polycystic Ovarian Syndrome Health-Related Quality of Life Questionnaire.

The Polycystic Ovary Syndrome Questionnaire is a reliable instrument for measuring health-related quality of life. This study aimed to develop a Malay version of the Polycystic Ovary Syndrome Questionnaire and to evaluate the health-related impact of Malaysian women with polycystic ovary syndrome. The participants were women who were diagnosed with polycystic ovary syndrome using Rotterdam criteria in a gynecology clinic. Reliability was determined by internal consistency using Cronbach's coefficient alpha and test-retest reliability using an intra-class correlation coefficient. Validity was assessed through convergent and discriminant validity. Examining the correlation between similar content of the Malay version of the Polycystic Ovary Syndrome Questionnaire and the SF-36 assessed the convergent validity. The discriminant validity was assessed using the known group comparison. Cronbach's alpha coefficient was over 0.70 for the total scale and over 0.60 for each subscale. Known group comparison supported the discriminant validity. The Malay version of the Polycystic Ovary Syndrome Questionnaire differentiated between the subgroups of women who differed in polycystic ovary syndrome-specific symptoms. Convergent validity was consistent with the good positive correlation between related subscales of the two instruments. Polycystic ovary syndrome women in Malaysia scored the lowest for the weight (3.74) and infertility (3.41) domains, thereby indicating worse health status in these domains. Body hair (5.42) was the least troublesome for the local population. The Malay version of the Polycystic Ovary Syndrome Questionnaire is a reliable and valid tool for assessing the health-related quality of life among women in the local population. It can be used to objectively assess the quality of life among Malaysian women with polycystic ovary syndrome and evaluate their responsiveness to treatment modalities.

PCOS and Role of Cumulus Gene Expression in Assessing Oocytes Quality.

The global infertility rate has been declining from year to year. PCOS is one of the treatable accountable causes contributing to anovulatory infertility. Nevertheless, the success rate of treatments and live-birth outcomes especially involving assisted reproductive techniques is still not very promising. There is a reduction in the development potential of oocytes and high-quality embryos in PCOS patients compared to non-PCOS patients. A critical step in IVF treatment is the assessment of oocyte and embryo competence before embryo transfer. Oocytes in metaphase II are very fragile. Repeated morphological assessment on these oocytes may directly impair the quality and affect the whole process. Identification of potential biomarkers especially in the cumulus cells oocytes complex will help to predict the outcome and may create space for improvement. This review has explored gene expression in cumulus cells with regards to oocytes quality in both normal and PCOS women. The gene expression was classified according to their physiological function such as the contribution on cumulus expansion, cumulus cells apoptosis, and glucose metabolism. Collectively, the review suggested that positive expression of HAS2, PTX3, GREM1, and VCAN may correlate with good quality oocytes and can be used as an indicator among PCOS women.

Ovarian tissue cryopreservation in Malaysia: a case series.

OBJECTIVES: We aim to discuss the hematological cancer cases that opted for ovarian tissue cryopreservation (OTC) as fertility preservation before the gonadotoxic chemotherapy agent. CASE PRESENTATION: The ovarian tissue cryopreservation (OTC) was started in August 2020 in our center. Up to now, there were four cases have been performed and included in this report. The ovarian tissue cortex was cryopreserved with cryoprotectant using Kitazato™ (Tokyo, Japan) media and fit in the closed system devices. A total of four post-OTC patients were included. The mean age was 24 years old, whereas the mean serum AMH level was 30.43 pmol/L. Most of them were diagnosed with lymphoma, except one was leukemia. All of them received additional GnRH analog following OTC as a chemoprotective agent before cancer treatment. Currently, they are recovering well and on regular follow-up with the hematological department. CONCLUSIONS: Although The OTC is an ultimate option for prepubertal girls, it can be proposed as a good strategy for adult cancer women who could not delay cancer therapy.

Single Dose Gonadotropin-Releasing Hormone Agonist Luteal Support in Fresh Embryo Transfer: Variation in Timing, Type, and Dosage.

OBJECTIVES: To evaluate the effects of the addition of single-dose GnRH agonist to the routine progestogens use for luteal phase support on IVF outcome as compared to progestogens only. METHODS: This is a retrospective case-control study on selected patients who underwent IVF treatment with fresh embryo transfer (ET) under Medically Assisted Conception Unit, University Kebangsaan Malaysia Medical Center for the period of June 2015-June 2018. A higher dose of 0.2 mg subcutaneous Decapeptyl was administered 2 days before fresh ET concurrent with routine progestogen support. Patients with different luteal phase regimes, frozen embryo transfer and medical records with missing data were excluded. Their medical records were reviewed, and data analyzed. The pregnancy outcomes measured included biochemical pregnancy rates, clinical pregnancy rates, live birth rates and miscarriage rates. RESULTS: A total of 786 patients were analyzed. Four hundred forty-four patients were given luteal phase support with progestogens and GnRH agonist, whereas 342 patients served as control were given progestogens only. The study group showed higher biochemical pregnancy rate (47.7 vs. 44.4%,), clinical pregnancy rate (25.7 vs. 23.4%) and livebirth rate (24.3 vs. 22.2%), respectively but not statistically significant. The rate of miscarriage among the study group was lower (4.5% vs 9.4%) compared to the progestogen group alone. Nonetheless, the OHSS rate was slightly increased in the study group (4.5 vs. 3.5%) despite using a mild stimulation protocol. CONCLUSIONS: New regime of GnRH agonist luteal support in addition to the standard progestogen support was found to be beneficial in overall IVF outcome.

Pre-induction cervical assessment using transvaginal ultrasound versus Bishops cervical scoring as predictors of successful induction of labour in term pregnancies: A hospital-based comparative clinical trial.

OBJECTIVE: To evaluate the association between transvaginal ultrasound scan of cervix and Bishop's score in predicting successful induction of labour, cut-off points and patients' tolerability and acceptance for both procedures. DESIGN: A comparative clinical trial. SETTING: A tertiary hospital in Selangor, Malaysia. PARTICIPANTS: 294 women planned for elective induction of labour for various indications were included. All women had transvaginal ultrasound to assess the cervical length and digital vaginal examination to assess the Bishop cervical scoring by separate investigators before induction of labour. PRIMARY OUTCOME MEASURE: To evaluate the association of the cervical length by transvaginal ultrasound scan and Bishop score in predicting successful induction of labour. SECONDARY OUTCOME MEASURE: Variables associated with successful induction of labour and patients' tolerability and acceptance for transvaginal ultrasound scan of cervix. RESULTS: There was no statistically significant difference among the vaginal and Caesarean delivery groups in terms of mean maternal age, height, weight, body mass index, ethnicity and gestational age at induction. Vaginal delivery occurred in 207 women (70.4%) and 87 women (29.6%) delivered via Caesarean section. There was a high degree of correlation between the cervical length and Bishop score (r-value 0.745; p <0.001). Sonographic assessment of cervical length demonstrated a comparable accuracy in comparison to Bishop score. Analysis using ROC curves noted an optimal cut-off value of ≤27mm for cervical length and Bishop score of ≥ 4, with a sensitivity of 69.1% vs 67%, specificity 60.9% vs 55%, and area under the curves (AUCs) of 0.672 and 0.643 respectively (p <0.001). Multivariate logistic regression analysis demonstrated that parity (OR 2.70), cervical length (OR 0.925), Bishop score (OR 1.272) and presence of funnelling (OR 3.292) were highly significant as independent predictors of success labour induction. Women also expressed significantly less discomfort with transvaginal ultrasound compared with digital vaginal examination. CONCLUSION: Sonographic assessment of cervical measurement predicts the success of induction of labour with similar diagnostic accuracy with conventional Bishop score.

Amniotomy and early oxytocin infusion vs amniotomy and delayed oxytocin infusion for labour augmentation amongst nulliparous women at term: A randomised controlled trial.

OBJECTIVE: to compare the effect of amniotomy with early vs delayed oxytocin infusion on successful vaginal delivery. DESIGN: randomised controlled trial of nulliparous women with spontaneous labour at term. SETTING: labour suite of a university teaching hospital in Kuala Lumpur, Malaysia. PARTICIPANTS: 240 women were included (120 randomised into two arms). INTERVENTIONS: the randomisation sequence was generated using a computer randomisation program in two blocks: oxytocin infused early following amniotomy; and oxytocin infused 2 h after amniotomy. MEASUREMENTS AND FINDINGS: labour duration, mode of delivery, oxytocin dosage used, uterine hyperstimulation, postpartum haemorrhage, Apgar score and admission to the neonatal intensive care unit were recorded. No differences in vaginal delivery rate (62.9% vs 70.9%; p = 0.248) and second-stage labour were found between the early and delayed oxytocin infusion groups (21.2 ± 18.3 min vs 25.5 ± 19.9 min; p = 0.220). The mean interval from amniotomy to vaginal delivery was significantly shorter for the early group (5.8 ± 1.7 h vs 7.0 ± 1.9 h; p = 0.001), and more women in the early group delivered during/before the planned review at 4 h after amniotomy (53.6% vs 10.6%; p<0.001). Maximum oxytocin usage was lower in the early group (5.6 ± 4.4 mL/hour vs 6.8 ± 5.3 mL/hour; p = 0.104). KEY CONCLUSIONS: early oxytocin augmentation following amniotomy could be employed in low-risk primigravida, given that it is associated with a shorter labour duration without jeopardising maternal or neonatal outcomes. IMPLICATIONS FOR PRACTICE: low-risk primigravida benefit from early oxytocin infusion following amniotomy, and this can be offered as an additional practice in labour room care.

A fine tuning of embryo loading technique by eliminating the air bubble in the outer sheath of embryo catheter among women undergoing IVF treatment.

OBJECTIVES: The role of air bubbles in bracketing the embryo-containing medium in inner catheter during embryo transfer (ET) has already been established. However, the role of air bubbles in outer catheter (OC) during implantation is yet to be determined. This study aimed to compare the implantation rates between women who have undergone ET with or without ASP (Vitrolife®; Sweden), a medium use for oocyte retrieval and rinsing in OC embryo catheter. The purpose of introducing the ASP medium to the OC was to eliminate air bubbles in that space during implantation. METHODS: A total of 312 women were randomly divided into two groups with 156 participants each group. In Group A, ASP medium was used during ET, whereas in Group B, no ASP medium was utilized. Positive implantation was defined as serum beta-hCG level >5 mIU/mL taken on the 7th day following ET. RESULTS: The average age of the majority of the participants was 30-39 years and had at least 4-5 years of subfertility. The unexplained subfertility was the prominent cause of ET failure in both groups. In most of the participants in both groups, ET was done using fresh embryo cycles with good to excellent embryo grades. After the ASP medium was manipulated in the OC in both groups, the positive implantation rate was not different in both groups (p>0.05). CONCLUSIONS: The elimination of air bubbles in OC by using the ASP medium during ET did not confer an additional benefit nor exert a negative impact on implantation rate.