Antenatal Corticosteroids to Asian Women Prior to Elective Cesarean Section at Early Term and Effects on Neonatal Respiratory Outcomes.

This exploratory study aimed to evaluate the effects of antenatal corticosteroids in singleton pregnancies of Asian women prior to elective cesarean section (CS) at early term on neonatal respiratory outcomes. METHODS: This is a pilot and pragmatic randomized trial conducted at a university hospital in Malaysia. Women with singleton pregnancies planned for elective CS between 37+0 and 38+6 weeks gestation were randomly allocated into the intervention group, where they received two doses of IM dexamethasone 12 mg of 12 h apart, 24 h prior to surgery OR into the standard care, control group, and both groups received the normal routine antenatal care. The primary outcome measures were neonatal respiratory illnesses, NICU admission and length of stay. RESULTS: A total of 189 patients were recruited, 93 women in the intervention group and 96 as controls. Between the steroid and control groups, the mean gestation at CS was similar, 266.1 ± 3.2 days (38 weeks) vs. 265.8 ± 4.0 days (37+6 weeks), p = 0.53. The mean birthweight of infants was 3.06 ± 0.41 kg vs. 3.04 ± 0.37 kg, p = 0.71. Infants with respiratory morbidities were primarily due to transient tachypnea of newborn (9.7% vs. 6.3%), and congenital pneumonia (1.1% vs. 3.1%) but none had respiratory distress syndrome. Only four infants required NICU admission (2.2% vs. 3.1%, p = 0.63). Their average length of stay was not statistically different; 3.5 ± 2.1 days vs. 5.7 ± 1.5 days, p = 0.27. CONCLUSIONS: Elective CS at early term before 39 weeks was associated with a modest overall incidence of neonatal respiratory illness (10.1%) in this Asian population. Antenatal dexamethasone did not diminish infants needing respiratory support, NICU admission and length of stay.

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.

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.

Pregnancy outcomes in systemic lupus erythematosus (SLE) women.

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory condition with multi-organ involvement predominantly affecting young women. There are very limited studies in pregnancy in Asian SLE patients and therefore we embarked on this study to identify pregnancy outcomes of Malaysian women with SLE. Materials and methods We performed a retrospective study of pregnancy outcomes in SLE patients in our institution from January 2007 to December 2014. A total of 71 pregnancies from 44 women were analysed. Results The mean age of our cohort was 30.5 ± 3.9 years. The rate of active disease at conception, antiphospholipid syndrome and lupus nephritis were 22.5%, 32.4% and 57.7% respectively. SLE flare occurred in 33 out of 71 pregnancies whereas 19 pregnancies were complicated with preeclampsia. The livebirth rate for our cohort was 78.9%, whilst preterm delivery was 42.9%. On univariate analysis, active disease and flare in pregnancy were both strongly associated with foetal loss and preterm delivery. Lupus nephritis (p = 0.011), SLE flare (p = 0.008) and antiphospholipid syndrome (p = 0.032) significantly increased the risk of preeclampsia. Aspirin and hydroxychloroquine were protective against foetal loss [odds ratio (OR) 0.12] and preeclampsia (OR 0.25), respectively. On multivariate analysis, active disease was a predictor of SLE flare (p = 0.002) and foetal loss (p = 0.018) and SLE flare was the main predictor of preterm delivery (p = 0.006). Conclusions Pregnancies in women with SLE should be planned and aspirin and HCQ use were beneficial in reducing adverse pregnancy outcomes.

A case of post-splenectomy transfusion-dependent homozygous beta-thalassemia major complicated with myocardial siderosis and osteoporosis and usage of iron-chelating therapy with deferiprone in pregnancy.

Beta-thalassemia major is a subtype component of hemoglobinopathies; autosomal recessive disorders complicated with anemia that affect at least 50,000 babies each year. It contributes to problems in reproductive entities such as infertility due to iron deposition in the endocrine organs, which leads to malfunction of the hypothalamus-pituitary axis. Due to this, there have been very few pregnancies discovered and reported with this type of condition as they usually required an ovulation-induction agent with assisted reproductive technique to achieved pregnancy. We report a successful spontaneous pregnancy in a woman with beta-thalassemia major who underwent splenectomy with lifelong transfusion-dependence complicated with myocardial siderosis and osteoporosis. The close monitoring and regular blood transfusion are a core of successful support to this type of pregnancy. The unintentional consumption of Fosamax, hydroxyurea and deferiprone (Ferriprox) up till 20 weeks of gestation did not show any adverse effects on fetal well-being. As expected, this pregnancy ended with the preterm delivery via cesarean section due to intrauterine growth restriction with oligohydramnios, and currently, this child is thriving. We concluded that pregnancy is not a contraindication in beta-thalassemia major; complex individual care is needed to achieve a safe outcome for the mother.

Reviewing the role of progesterone therapy in endometriosis.

Endometriosis is a benign, chronic inflammatory condition characterized by the presence and growth of endometrial implants outside the uterine cavity. The cause of endometriosis is multifactorial. It is due to the diversity of hypothesis and plausibility of hormonal alterations which could play a major role. Evidence has shown that progesterone resistance is a key factor for endometriosis sufferers. Medical therapy can avoid surgical intervention, which may lead to a reduced in ovarian reserve, and its effects of earlier menopause and reduced fecundity. Progesterone receptor isoform has provided new insight as the potential treatment. Progestin, anti-progestin and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating. Numerous types of these medications have been used on and off labeled to treat endometriosis with varying success. This review aims to consolidate series of clinical trials using progestins in endometriosis.

Sodium pentosan polysulfate efficacy as thromboprophylaxis agent in high-risk women following gynecological surgery.

AIM: Sodium pentosan polysulfate (Na-PPS) is a plant-based agent that has similar action with low-molecular-weight heparin. It inhibits factor Xa, preventing blood clot formation. To date, its use in clinical practice as thromboprophylaxis agent is still limited. In addition, the efficacy and safety profile of this agent was not robustly reported globally, especially for countries with major Muslim population. We hypothesized that Na-PPS was equally effective as the standard thromboprophylaxis. We aim to compare the efficacy and safety of Na-PPS against standard agent (fondaparinux or enoxaparin). METHODS: This was a randomized control, open-label trial. Women underwent major gynecological surgery were randomized to receive either subcutaneous 50 mg of Na-PPS twice daily or subcutaneous enoxaparin 40 mg once daily. Fondaparinux 2.5 mg once daily was given to Muslim women as an alternative to enoxaparin. The treatment was started 6 h postoperatively, for at least 3 days. All the patients received thromboembolic deterrent stockings. The primary efficacy outcome was venous thromboembolism up to 3 days postsurgery. The main safety outcomes were minor and major bleeding. RESULTS: Among 109 participants, there was no incidence of venous thromboembolism. None of the women developed major bleeding. Minor bleeding was observed in 28.3% (15/53) and 5.4% (3/56) of Na-PPS and standard thromboprophylaxis group, respectively (P = 0.001). CONCLUSION: Na-PPS was associated with increased risk of minor bleeding. There was insufficient data to conclude its efficacy as thromboprophylaxis. Further research is needed to evaluate Na-PPS safety as a standard thromboprophylactic agent.

Do exercises improve back pain in pregnancy?

Objective To assess the efficacy of an exercise program towards reducing back pain in pregnant women. Methods In this prospective control study, 145 low risk pregnant women who scored more than 20 for functional limitation assessment were recruited. The severity of back pain was assessed using the visual analoque scale (VAS) and the functional limitation was assessed using the Oswestry disability questionnaire (ODQ). All participants were informed of back care measures and provided with Paracetamol as an adjunct analgesia. The intervention group will have a session with a trained physiotherapist. Subsequently, all participants will be required to fill in a similar questionnaire regarding pain intensity and functional limitation assessment after 6 weeks post-intervention. Results There was a significant reduction in the VAS score and improvement in functional ODQ score in the intervention group. The median usage of Paracetamol as an analgesia to control back pain in the control group was 500 mg higher than the intervention group. There was a weak association of age, parity, duration of back pain, and body mass index with functional ODQ score at 6 week following intervention. Conclusion The back pain exercise reducing program was effective in reducing back pain intensity and analgesia usage with a significant improvement in functional ability.

Dydrogesterone support following assisted reproductive technique (ART) reduces the risk of pre-eclampsia.

BACKGROUND: Pre-eclampsia (PE) contributes to poor maternal morbidity and mortality. Progesterone is hypothesised to reduce the risk of PE. AIM: To determine the effect of progestogen supplementation during assisted reproductive technique (ART) in reducing the incidence of PE. METHOD: A retrospective comparative analysis among 1140 pregnancies between January 2006 and March 2015 conducted in a tertiary centre. A total of 570 pregnancies who conceived following ART with progesterone supplementation (study group) and an age-matched spontaneous pregnancies, without progesterone supplementation (control group, n=570) were included in the analysis. The study group received progesterone support following ART or intrauterine insemination (IUI) until 14-16 weeks' gestation. RESULTS: The rate of PE was significantly lower in the study group compared to control group (8.4% vs. 14.2%, p<0.05). Women supplemented with dydrogesterone only showed a lower PE incidence as compared to women received a combination of dydrogesterone and hydroxyprogesterone caproate, however, it was not statistically significant (6.9% vs. 9.9%; 6.9%; p=0.2).

Spontaneous conception following GnRHa and progestogen therapy in adenomyosis.

Adenomyosis is a common gynaecological disorder that is associated with infertility and miscarriage. We report a case of adenomyosis presented with urinary retention and infertility. The patient successfully conceived spontaneously following GnRHa followed by progestogen therapy. This treatment option might provide a synergistic effect in improving fertility and pregnancy outcome for women with adenomyosis. This modality has no potential surgical risk; it minimises the long-term side effects of GnRHa and also provides luteal support.

Use of hydroxyprogesterone caproate to prevent preterm labour in uterine didelphys: a case report.

Congenital uterine anomalies have been associated with poor reproductive outcome, which include recurrent miscarriage, abruptio placenta, intra-uterine growth restriction and preterm delivery. Here, we report a case: 36 years old, G3P2, known case of uterine didelphys, with history of preterm birth, who successfully carried her pregnancy till term with weekly intramuscular injection of 250 mg hydroxyprogesterone caproate (®Proluton Depot, Zuellig Pharma).

The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study.

The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.

Successful external cephalic version: factors predicting vaginal birth.

PURPOSE: To determine the maternal and fetal outcomes of successful external cephalic version (ECV) as well as factors predicting vaginal birth. METHODS: The ECV data over a period of three years at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1 September 2008 and 30 September 2010 was reviewed. Sixty-seven patients who had successful ECV were studied and reviewed for maternal, fetal, and labour outcomes. The control group comprised patients with cephalic singletons of matching parity who delivered following the index cases. RESULTS: The mean gestational age at ECV was 263 ± 6.52 days (37.5 weeks ± 6.52 days). Spontaneous labour and transient cardiotocographic (CTG) changes were the commonest early adverse effects following ECV. The reversion rate was 7.46%. The mean gestational age at delivery of the two groups was significantly different (P = 0.000) with 277.9 ± 8.91 days and 269.9 ± 9.68 days in the study group and control groups, respectively. The study group needed significantly more inductions of labour. They required more operative deliveries, had more blood loss at delivery, a higher incidence of meconium-stained liquor, and more cord around the neck. Previous flexed breeches had a threefold increase in caesarean section rate compared to previous extended breeches (44.1% versus 15.2%, P = 0.010). On the contrary, an amniotic fluid index (AFI) of 13 or more is significantly associated with a higher rate of vaginal birth (86.8% versus 48.3%, P = 0.001). CONCLUSIONS: Patients with successful ECV were at higher risk of carrying the pregnancy beyond 40 weeks and needing induction of labour, with a higher rate of caesarean section and higher rates of obstetrics complications. Extended breech and AFI 13 or more were significantly more likely to deliver vaginally postsuccessful ECV. This additional information may be useful to caution a patient with breech that ECV does not bring them to behave exactly like a normal cephalic, so that they have more realistic expectations. However, these predictive factors needed further confirmation and hopefully, in the future, they would be able to further enhance counselling prior to ECV.

Comparison between AmniSure placental alpha microglobulin-1 rapid immunoassay and standard diagnostic methods for detection of rupture of membranes.

Objective. To determine the diagnostic accuracy of placental alpha microglobulin-1 assay and standard diagnostic methods for detecting rupture of membrane. Study Design. Prospective diagnostic study, between June 2011 to November 2011 at a tertiary centre. Initial evaluation included both the standard diagnostic methods for rupture of membranes and placental alpha microglobulin-1 immunoassay. The actual rupture of membranes was diagnosed on review of the medical records after delivery (absence of membrane or a positive pad chart). Main Outcome Measures. Placental alpha microglobulin-1 immunoassay and standard diagnostic methods for diagnosis of rupture of membrane. Results. A total of 211 patients were recruited. At initial presentation, 187 patients (88.6%) had ruptured membranes, while 24 patients (11.4%) had intact membranes. Placental alpha microglobulin-1 immunoassay confirmed rupture of membranes at initial presentation with a sensitivity of 95.7% (179 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (179 of 179), and negative predictive value of 75.0% (24 of 32). By comparison, the conventional standard diagnostic methods had a sensitivity of 78.1% (146 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (146 of 146), and negative predictive value of 36.9% (24 of 65) in diagnosing rupture of membrane. Conclusion. Placental alpha-microglobulin-1 immunoassay is a rapid and accurate method for confirming the diagnosis of rupture of membrane. It was superior to conventional standard diagnostic methods (pooling, nitrazine, and ferning), the nitrazine test alone or fern test alone.

Microarray profiling of secretory-phase endometrium from patients with recurrent miscarriage.

The aim of the present study was to identify differentially expressed genes and their related biological pathways in the secretory phase endometrium from patients with recurrent miscarriage (RM) and fertile subjects. Endometrial samples from RM and fertile patients were analyzed using the Affymetrix GeneChip® ST Array. The bioinformatic analysis using the Partek Genomic Suite revealed 346 genes (175 up-regulated and 171 down-regulated) that were differentially expressed in the endometrium of RM patients compared to the fertile subjects (fold change ≥1.5, p<0.005). Validation step using quantitative real-time polymerase chain reaction (qPCR) confirmed a similar expression pattern of four exemplary genes: one up-regulated gene (fibroblast growth factor 9, FGF9) and three down-regulated genes: integrin ß3 (ITGB3), colony stimulating factor 1 (CSF1) and matrix-metalloproteinases 19 (MMP19). The Gene Set Enrichment Analysis (GSEA) and the Pathway Studio software have found 101 signaling pathways (p<0.05) associated with the affected genes including the FGFR3 /signal transducer and activator of transcription (STAT) pathway and the CSF1R/STAT pathway. Cell adhesion, cell differentiation and angiogenesis were among biological processes indicated by this system. In conclusion, microarray technique is a useful tool to study gene expression in the secretory phase-endometrium of RM patients. The differences in endometrial gene expressions between healthy and RM subjects contribute to an increase in our knowledge on molecular mechanisms of RM development and may improve the outcome of pregnancies in high-risk women with RM.

A case report: metastatic choriocarcinoma to the gum.

Choriocarcinoma is a rare neoplasia with a tendency of distant metastasis although highly sensitive to chemotherapy renders a good prognosis and outcome. Lungs, liver and cerebral metastasis are commonly implicated with maxillofacial region rarely involved. We illustrate a case of overwhelming metastatic choriocarcinoma to lungs, liver, brain and to the extreme of gum metastasis. Decompressive craniectomy for intracranial bleeding, multiple transfusions to correct anaemia and coagulopathy were done before high-risk-regime chemotherapy. Despite this, due to fulminant multi-organs involvement she finally succumbed to death. In conclusion, gum bleeding in choriocarcinoma may suggest metastasis and poor prognosis.

Case report of ruptured non-communicating right rudimentary horn pregnancy: an acute emergency.

Ruptured pregnancy in the rudimentary horn of women who have had a vaginal delivery is rare and unpredictable. However, when undiagnosed, this condition could lead to maternal morbidity and mortality. We report a pregnancy at 19 weeks gestation presented with acute abdomen and hypovolemic shock. She was initially thought to have an intrauterine pregnancy with the provisional diagnosis of a ruptured uterus. Intraoperatively, a ruptured non-communicating right rudimentary horn with ex utero pregnancy was discovered.