Screening for cervical cancer: Choices & dilemmas.

Cervical cancer is the fourth most common cancer in women in the world. To eliminate cervical cancer by 2030, the World Health Organization has given the target of 70 per cent coverage of twice lifetime screening. A multitude of screening methods are available, including cytology, human papillomavirus (HPV) DNA testing and visual inspection tests. Precision tests, including molecular and protein biomarkers such as DNA methylation, p16 immunostaining, and HPV mRNA testing help to enhance specificity of the screening. Worldwide HPV DNA testing with or without cytology is used as a screening method of choice, while in resource-poor settings, visual inspection tests are recommended. The major hurdle is a uniform and systematic implementation with a recall method in the population. Besides, controversies still exist regarding strategies to manage HPV-positive women and developing guidelines to screen the vaccinated population.

Human telomerase RNA component (hTERC) gene expression and chromosome 7 ploidy correlate positively with histological grade of cervical intraepithelial neoplasia.

OBJECTIVE: Cervical cancer screening by primary human papilloma virus detection and cytology is fraught with low specificity and variable sensitivity, respectively. Cytology-histology correlation remains modest. Biomarkers associated with early genetic events in cervical squamous carcinogenesis and detectable in cytology material are likely to be relevant. Human telomerase RNA component (hTERC) gene overexpression and aneuploidy are promising candidates in view of their reported early and consistent association with cervical squamous oncogenesis. METHODS: We analysed hTERC gene expression and chromosome 7 ploidy by fluorescent in-situ hybridisation (FISH) in 50 women with cytological precursor squamous intraepithelial lesions and available histology outcomes. Results were expressed as percentages of cells showing ≥3 signals, mean signals/nucleus, and maximum amplitude across various cytology and histology categories. Proportions of positive cases were calculated from threshold values derived from 6 controls. Distribution of above indices with respect to ≥cervical intraepithelial neoplasia 2 (CIN2) was explored. RESULTS: For both genetic aberrations, there was significant positive correlation (for all indices) between the proportion of positive cases and worsening cytological and histological outcomes (P < .05), with significant intergroup differences (P < .05). High-grade lesions (≥CIN2) had significantly higher results compared to

Spectrum of Maternofetal Outcomes during Dengue Infection in Pregnancy: An Insight.

Dengue is a vector transmitted viral infection; tropical and subtropical countries see outbreaks of dengue each year. There is a paucity of literature on effects of dengue infection on pregnancy outcome and this prompted us to undertake a study for better understanding of pregnancy implications with dengue infection. Pregnant women admitted during the seasonal outbreak of dengue between September 2015 and October 2015 were studied and maternal and fetal outcomes in sixteen NS1Ag positive women were analysed. Out of sixteen women diagnosed with dengue fever, three had dengue shock syndrome (DSS) and eight had dengue haemorrhagic fever (DHF). The most common obstetric complication seen in 43% of the cases was oligohydramnios. Bleeding manifestations occurred in seven women and there were three maternal deaths. Perinatal complications included three intrauterine deaths, six nursery admissions, and one neonatal death. Thus dengue infection was associated with high maternal and perinatal mortality. In view of poor obstetric outcomes, this viral infection warrants early admission and prompt management.

Adolescent ovarian masses: A retrospective analysis.

A retrospective study was conducted to review incidence, clinical practice, surgical management and histology of adolescent ovarian masses in order to audit and improve future practices. Complete hospital records of all adolescents between 10 and 20 years who had undergone surgery for ovarian masses were analysed between November 2006 to 2014. Parameters analysed were age, clinical features, diagnosis, operative procedure and histopathology. Ninety-four patients were included in the study and among them, 37 had non-neoplastic masses, 30 had benign neoplasms while 27 had malignant tumors. The main clinical presentations were abdominal pain (54%) and abdominal mass (41%). Dermoid was the most common benign neoplasm while germ cell tumor was the most common malignant mass; dysgerminoma being the commonest (68%). Malignancy was more common in early adolescence (12 ± 4.8 years) while non-neoplastic masses were seen more frequently in late adolescence (17.7 ± 2.2 years). There was a fair correlation between ultrasound and histopathological diagnosis.

Community Screening for High-Risk Human Papilloma Virus Infection using Self-Sampling and 'Point-Of-Care' Test.

OBJECTIVE: HR-HPV types 16 and 18 are responsible for pre-invasive and invasive lesions of the cervix, accounting for 70-80% of the total subtypes. The aim of this study was to investigate the prevalence of high-risk HPV subtypes 16 and 18 in self-collected vaginal samples using real-time micro-PCR and to study the acceptability of self-sampling. METHODS: Eligible women (30-65 years) were screened from a semi-urban area of Uttarakhand (India) using self-sampling. High-risk HPV genotypes (16/31 and 18/45) were tested using real-time micro-PCR technique with results available in one hour. The positive results were validated by standard RT-PCR for high-risk HPV 16, 18, separately and for 12 other high-risk genotypes, combined. Ease of the procedure, level of comfort, and recommendation to other women were studied and the acceptability of self-sampling was analyzed using the Likert scale. RESULT: Of 975 eligible women screened, 45 participants tested positive for HR-HPV (16/31,18/45) using real-time micro-PCR with a prevalence of 4.6%. Positive samples were further tested through routine RT-PCR and 60% were found to be HR-HPV 16 and 18 positive. For self-sampling, 96.72% (n=943) participants were 'very satisfied' and 94.15% (n=918) found self-sampling to be 'very comfortable' and 88.51% (n=863) stated that they will strongly recommend this test to other eligible women in the community. CONCLUSION: We conclude that HR-HPV testing with limited genotyping showed a prevalence of 4.6%, 60% of these were HPV 16/18 positive. Point of care testing was feasible in the community and self-sampling was acceptable.

A novel technique of vagino-hysteroscopy using alginate gel interface: A proof of concept study.

OBJECTIVE: To compare the feasibility of vagino-hysteroscopy using alginate gel Interface (VAGI) with conventional vaginoscopic hysteroscopy (CVH). METHODS: Thirty women undergoing diagnostic vagino-hysteroscopy were randomly allocated into Group I (VAGI): Alginate occluder was used at introitus to facilitate hydrodistension during hysteroscopy; or Group II: Underwent no-touch hysteroscopy. Primary outcome was feasibility, defined as successful visualization of uterine cavity. Secondary outcomes included operative time, hydrostatic pressures for optimum visualization, pain experienced by patient on visual analog scale, maneuverability and surgeon satisfaction. Data analysis was performed using χ2 and Fisher exact tests for qualitative variables and Student t test for quantitative variables. RESULTS: VAGI was significantly better than CVH (80% vs. 33.3%; relative risk 8, P = 0.025). With VAGI, optimum visualization was achieved at significantly lower pressures at all levels (vagina, P = 0.034; cervix, P = 0.01; uterus, P < 0.001), in less time (P = 0.007), and using less irrigation fluid (P < 0.001). Surgeon satisfaction was significantly higher for VAGI (P = 0.009). Subgroup analysis showed higher likelihood of success of VAGI in women who were premenopausal (P = 0.015), younger than 45 years (P = 0.024), and had a history of vaginal birth (P = 0.03). CONCLUSIONS: VAGI is quicker to perform and provides optimum visualization at much lower pressures than CVH. Use of alginate is patient friendly and yields higher surgeon satisfaction rate.

Cervical Cancer Screening Coverage at Tertiary Care Institutes Across India.

OBJECTIVES: The 70% screening coverage target proposed in the global cervical cancer elimination strategy is not achieved even at tertiary centres in India. A situational analysis was done to assess the currently existing facilities and barriers in tertiary care institutes. METHODS: This cross sectional multicentric study was conducted from August to September 2021 in six tertiary care institutes across India. Women aged 30-49 years attending outpatient services (OPD) were invited for cervical screening. Women and health care professionals (HCPs) were administered structured questionnaires to assess knowledge, attitude and practices regarding cervical cancer screening services. RESULTS: Out of 6709 eligible women who attended OPD, 1666 (24.8%; range:19-57%) received screening. Availability of screening kits was limited to 10-25 Pap/HPV tests per day. Visual inspection with acetic acid (VIA) and HPV testing were offered only at certain centres. Colposcopy and treatment facilities were optimal at all centres. Knowledge, attitude and practices were analysed for 1800 women: 45.7% had heard of cervical cancer, 78.0% did not know that it is preventable, 75.8% never heard about screening. Common symptoms correctly identified included postmenopausal bleeding (4.8%), postcoital bleeding (5.7%), intermenstrual bleeding (5.8%) and vaginal discharge (12.4%). Risk factors were identified by minority: poor menstrual hygiene (6.6%), oral contraceptive pill use (6.4%), multiparity (4.4%), and HPV infection (3.0%). Out of 21, mean total knowledge score (MTKS) was 2.07± 2.67. Out of 317 HCPs, 96.5% knew that cervical cancer is caused by HPV infection, is preceded by premalignant stage, and that it is preventable by screening and treatment (80.1%). Knowledge about screening modalities was present in 87.4% for cytology, 75.1% for VIA, 68.8% for HPV test. MTKS of HCPs was 20.88±6.61 out of 32. CONCLUSION: Even at tertiary centres, limited availability of HPV tests, reluctance to implement VIA and lack of awareness among women remain the major barriers.

Extrauterine Adenomyosis Coexistent with Mature Cystic Teratoma: An Extremely Rare Entity.

Extrauterine adenomyosis is a rare entity. We present a case of a 32-year-old female who presented with this rare entity as a large abdominal mass and was a diagnostic and pathological dilemma.

Growing teratoma syndrome: a surgical conundrum.

Growing teratoma syndrome (GTS) is a tumour growth, which contains mature teratomatous elements during or after chemotherapy for malignant germ cell tumours. Surgery is the only potential treatment option for GTS because these growing teratomas are resistant to chemotherapy and radiation therapy. Extensive surgeries may be needed in GTS with multivisceral resections to achieve no residual disease status. This report presents a case of GTS treated with multiple surgical resections in a woman with malignant immature teratoma ovary in her early thirties; she is disease free after 1 year of treatment.

PAX1 Methylation Status in Cervical Scrapes as Novel Diagnostic Biomarker in CIN 2/3 and Invasive Squamous Cell Carcinoma.

Objectives: DNA methylation of paired box-1 (PAX-1) gene has been shown to be a potential biomarker for the detection of high-grade cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer. The objective of this pilot study was to quantify and compare methylation percentage of PAX1 gene in benign cervical lesion, pre-invasive and invasive cervical cancer. Methods: A total of 200 screen positive women (VIA, VILI and Pap test) underwent colposcopy. Cervical scrapes taken were taken and stored for DNA analysis and PAX 1 methylation status. Women with Swede score of 5 or more (n = 98) were biopsied. Cervical scrapes and biopsy were taken from women with obvious cervical growth (n = 14), without prior colposcopy. Sixty women were recruited to the study and allocated into three groups on the basis of histopathology, i.e., benign cervix (Group 1; n = 20), CIN 2/3 (Group 2; n = 20) and invasive cervical carcinoma (Group; n = 20). PAX 1 methylation percentage was calculated from the DNA extracted from the cervical scrapes of the women recruited. Results: The mean PAX1 methylation percentage in benign lesions, CIN 2/3 and invasive cancer was 9.58% (SD ± 2.37%), 18.21% (SD ± 2.67%) and 24.34% (SD ± 4.09%), respectively, with p-value of < 0.001. Conclusions: PAX 1 gene methylation has a promising role in identifying high-grade lesions and invasive cancer.

Implementing the Practice of Birth Companion in Labor During the COVID-19 Pandemic: A Quality Improvement Endeavor in India.

Objective We aim to implement the practice of birth companions (BC) (from 0% to 90%) during labor to provide respectful maternity care (RMC) during the coronavirus disease 2019 (COVID-19) pandemic. Methods This was a prospective quality improvement (QI) study conducted in the Department of Obstetrics and Gynecology at All India Institute of Medical Sciences (AIIMS), Rishikesh, India. The methodology given by the World Health Organization (WHO)'s Point of Care Continuous Quality Improvement (POCQI) manual was followed, and standard tools of quality improvement were used to attain the objective. Results The QI team conducted a cause and effect analysis to understand the reasons why birth companions were not allowed during childbirth. The Pareto principle derived at three most important causes of the problem: absence of a defined policy, ignorance of guidelines promoting BC even during the pandemic, and relatives could enter wards only after a negative reverse transcriptase polymerase chain reaction (RTPCR) report, which could take up to 48 hours. Multiple change ideas were tested by means of Plan-Do-Study-Act (PDSA) cycles that were successful in bringing about desired change and improvement in the delivery of quality healthcare. Conclusion QI methodology was effective in promoting and achieving more than 90% birth companionship in labor and thus helpful in providing respectful maternity care even during the COVID-19 pandemic.

Bleomycin-Induced Flagellate Dermatitis: Revisited.

Flagellate dermatitis caused by bleomycin is a rare side effect with a distinctive pattern of whip-like, linear streaks. The clinical presentation has become uncommon nowadays as bleomycin use in conventional chemotherapy regimens has decreased. We present a case of a 30-year-old female diagnosed with ovarian germ cell tumour, managed with bleomycin, etoposide, and cisplatin (BEP) and later developed a widespread rash indicative of classic flagellate dermatitis. This brief report emphasizes the significance of detection and management of this transient dermatological complication in patients receiving bleomycin.

Evaluation of frozen section biopsy for fast track diagnosis of endometrial pathology in high-risk women with abnormal uterine bleeding.

OBJECTIVE: To study the accuracy of frozen section biopsy for endometrial pathology in high-risk women with abnormal uterine bleeding (AUB). STUDY DESIGN: A case-control study was conducted between November 2017 to April 2019, a total of 150 women with postmenopausal bleeding, perimenopausal AUB, and high-risk women of age < 40 years with AUB were recruited. All women underwent transvaginal sonography and Doppler, based on age-appropriate endometrial thickness cut-offs 80 women then underwent hysteroscopy. Based on hysteroscopy, women suspicious of malignancy were taken as cases (n = 40) and those with benign findings as controls (n = 40). All cases and controls underwent dilatation and curettage (D & C) with frozen section (FS) and routine histopathology. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR), negative LR, and overall test accuracy of FS were 90.9%, 93.19%, 83.33%, 96.19%, 13.8, 0.1 and 86.25% respectively for diagnosing endometrial hyperplasia and cancer taking histopathology as the gold standard. Correlation between frozen section biopsy and histopathology was highly significant (p < 0.001) on D & C specimens and the level of agreement was good (K = 0.778). CONCLUSION: In women suspicious of malignancy on hysteroscopy, frozen section has high accuracy on D&C specimen and can be used to diagnose endometrial hyperplasia and cancer in an effort to fast-track investigations and work-up for definitive treatment while awaiting final histopathology.

Abdomino-peritoneal tuberculosis masquerading as ovarian cancer: a retrospective study of 26 cases.

PURPOSE: Evaluation of clinical, laboratory, and operative findings in women of abdomino-pelvic tuberculosis undergoing laparotomy for suspected ovarian cancer. METHODS: A retrospective analysis of 26 women who underwent laparotomy for ovarian cancer and found to have abdomino-pelvic tuberculosis in three hospitals of Delhi. RESULTS: The mean age was 34.65 years. Symptoms were menstrual dysfunction in 12 (46.2%), abdominal distension (8 women, 30.7%), abdominal pain (26 women, 100%), abdominal mass (5 women, 19.2%). Mean and standard deviation (SD) of Ca-125 levels were 594.22 ± 770.07. The mean ± SD of right and left tubovarian mass being 5.82 ± 3.94 cm and 5.81 ± 3.21 cm, respectively. Abdominal hysterectomy was done in 4 (15.4%) cases, right ovariotomy in 5 (19.2%), left Ovariotomy in 6 (23.1%), biopsies from right ovary 11 (42.3%), left ovary 7 (26.9%), omentum 10 (38.5%), peritoneum in 15 (57.7%). Tuberculous granuloma and AFB stain on histopathology were observed in all cases. CONCLUSION: Peritoneal tuberculosis with abdomino-pelvic masses was difficult to differentiate from ovarian cancer. Antitubercular drugs are the treatment of choice and complete surgery being difficult and hazardous should be avoided.

Oral micronized progesterone for prevention of preterm birth.

OBJECTIVE: To evaluate oral micronized progesterone (OMP) to prevent preterm birth (PTB). METHODS: A randomized, double-blind, placebo-controlled trial of 150 women with at least one PTB who received 100 mg of OMP or placebo twice a day from recruitment (18-24 weeks) until 36 weeks or delivery. RESULTS: PTB occurred in 29 (39.2%) women in the OMP group (n=74) compared with 44 (59.5%) in the control group (n=74, P=0.002). Mean gestational age at delivery was higher in the OMP group (36.1 vs 34.0 weeks, P<0.001). Fewer preterm births occurred between 28 and 31 weeks plus 6 days in the OMP group (RR 0.20; 95% CI, 0.05-0.73, P<0.001). Neonatal age at delivery (34 vs 32 weeks, P<0.001), birth weight (2400 vs 1890 g, P<0.001), NICU stay (>24 h, P<0.001), and Apgar scores (P<0.001) were more favorable in the OMP group, and fewer neonatal deaths occurred (3 vs 7, P=0.190). CONCLUSION: OMP reduced the risk of PTB between 28 and 31 weeks plus 6 days, NICU admissions, and neonatal morbidity and mortality in high risk patients.

Assessment of a Combination of Clinical Maneuvers in Evaluation of Post-Laparoscopic Pain: A Randomized Clinical Trial.

BACKGROUND: To assess the efficacy of the combined maneuvers in evaluation of post-laparoscopic pain. MATERIAL AND METHODS: A randomized controlled study was conducted. Sixty-four women were included in the study and were randomly divided into two groups. Intervention group received combined maneuvers such as intraperitoneal normal saline infusion, pulmonary recruitment maneuver and local bupivacaine instillation at port sites after laparoscopic surgery. Control group received routine care. MAIN OUTCOME MEASURES: Upper abdominal pain, shoulder pain and incision site pain were noted in both groups at 3, 6, 12, 24 and 48 h postoperatively. RESULTS: The median interquartile range (in centiles) of upper abdominal pain score 3, 6 and 12 h postoperatively in the intervention group was 1.0 (0.25-1.0), 1.0 (0.0-1.0) and 0.50 (0.0-1.0), and in the control group, the values were 2.0 (2.0-1.0), 2.0 (2.0-1.0) and 1.0 (0-1.0) at 3, 6 and 12 h, respectively (p < 0.000). The median interquartile range of shoulder pain score 3, 6 and 12 h postoperatively in the intervention group was 0.0 (0.0-1.0), 0.0 (0.0-0.75) and 0.0 (0.0-1.0), and in the control group, the values were 1.0 (0.0-2.0), 1.0 (0.0-1.75) and 1.0 (0-1.0) at 3, 6, and 12 h. The upper abdominal pain and shoulder pain relief was significantly more in the intervention group than in the control group in the first 12 h of surgery. CONCLUSION: Combined maneuvers could significantly reduce post-laparoscopic upper abdominal and shoulder pain.Clinical Trial CTRI Registration Number-CTRI/2017/07/0089, web address of CTRI-http://ctri.nic.in.

Neutrophil-to-lymphocyte ratio and platelet indices in pre-eclampsia.

OBJECTIVE: To compare the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and platelet indices between women with pre-eclampsia and normotensive pregnant women. METHODS: A cross-sectional study conducted from January to July 2017 at a tertiary care hospital in Delhi, India. The study compared pregnant women aged 18-40 years with pre-eclampsia diagnosed at term with healthy pregnant women matched for gestational age. Venous blood samples were drawn and complete blood count was analyzed. The parameters recorded were hemoglobin, red cell distribution width (RDW), platelet count, mean platelet volume (MPV), plateletcrit, and platelet distribution width. RESULTS: There were 67 women included in each group. NLR was higher in women with pre-eclampsia compared with the control group (6.8 ± 7.6 vs 3.0 ± 0.98; P=0.001). Both PLR (14.18 ± 14.4 vs 9.54 ± 3.6; P=0.012) and MPV (9.45 ± 1.19 vs 9.02 ± 1.1; P=0.029) were higher in the study group compared with the control group. Platelet count was lower in pre-eclamptic women compared with the control group (188 ± 89.7 vs 200.1 ± 62.36; P=0.014). RDW was also higher in the study group (P=0.025). CONCLUSIONS: The present study found that the inflammatory markers NLR, PLR, RDW, and MPV were higher in women with pre-eclampsia. Measuring NLR and PLR may be useful in predicting pre-eclampsia among women at high risk during prenatal follow-up.

Comparison of the AV Magnivisualizer device with colposcopy to detect cervical intraepithelial neoplasia using the Swede scoring system.

OBJECTIVE: To compare the AV Magnivisualizer with colposcopy to detect cervical intraepithelial neoplasia (CIN) using the Swede scoring system. METHODS: Cross-sectional study conducted in a tertiary care hospital from May 2017 to March 2018. One hundred women with positive results at visual inspection with acetic acid underwent cervical inspection using the Magnivisualizer followed by a colposcope. Biopsies were taken if the Swede score was greater than 4. Pregnant women, women with an obvious cervical growth, acute cervicitis, or prior cervical surgery were excluded. Diagnostic accuracy of the Magnivisualizer and colposcope was calculated for high-grade lesions (CIN 2/CIN 2+) and agreement was compared between the two modalities. RESULTS: The sensitivity, specificity, and positive and negative predictive values of the Magnivisualizer were 88.2%, 70.0%, 50.0%, and 94.6%, respectively, to detect high-grade lesions at a Swede score cutoff of 5 or more. The area under the curve for the Magnivisualizer was 0.80 (95% CI, 0.67-0.92), which was comparable with colposcopy (AUC 0.86; 95% CI, 0.76-0.96). There was very good agreement between the Magnivisualizer and colposcopy (κ=0.865, P<0.001) for high-grade lesions. CONCLUSION: The Magnivisualizer had high diagnostic accuracy to detect high-grade CIN in screen-positive women, which was comparable with colposcopy.

Oral progesterone for the prevention of recurrent preterm birth: systematic review and metaanalysis.

OBJECTIVE DATA: The purpose of this study was to perform a systematic review and metaanalysis of randomized controlled trials on oral progesterone compared with placebo or other interventions for preterm birth prevention in singleton pregnancies with previous spontaneous preterm birth. The primary outcome was preterm birth at <37 weeks gestation; the secondary outcomes included preterm birth rate at <34 weeks gestation, neonatal morbidity/death, and maternal side-effects. STUDY: Searches were performed in PubMed, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Register with the use of a combination of words related to "preterm birth," "preterm delivery," "progesterone," "progestogens," and "oral" from inception of each database to April 2018. Additionally, systematic reviews on progesterone for preterm birth prevention that were identified in our search were also reviewed for additional studies. We included all randomized trials of asymptomatic singleton gestations with previous spontaneous singleton preterm birth that had been randomized to prophylactic treatment with oral progesterone vs placebo, no treatment, or other preterm birth intervention. Exclusion criteria included quasirandomized trials, trials that involved women with preterm labor/membrane rupture at the time of randomization or multiple gestations. STUDY APPRAISAL AND SYNTHESIS METHODS: The risk of bias and quality of evidence were assessed for each study. All analyses were done with an intention-to-treat approach. The primary outcome was incidence of preterm birth at <37 weeks gestation; the secondary outcomes included preterm birth at <34 and <28 weeks gestation, maternal adverse events, maternal serum progesterone level, and neonatal morbidity and death. Summary measures were reported as relative risk or mean difference. I2 >30% was used to identify heterogeneity. RESULTS: The search strategy identified 79 distinct studies. Three trials on oral progesterone vs placebo (involved 386 patients: 196 in oral progesterone and 190 in placebo) met the inclusion criteria; there were no studies on oral progesterone vs other intervention that met inclusion criteria. Metaanalysis demonstrated a significantly decreased risk of preterm birth at <37 weeks gestation (42% vs 63%; P=.0005; relative risk, 0.68; 95% confidence interval, 0.55-0.84), preterm birth at <34 weeks gestation (29% vs 53%; P<.00001; relative risk, 0.55; 95% confidence interval, 0.43-0.71), and increased gestational age of delivery (mean difference, 1.71 weeks; 95% confidence interval, 1.11-2.30) with oral progesterone compared with placebo. There was a significantly lower rate of perinatal death (5% vs 17%; P=.001; relative risk 0.32; 95% confidence interval, 0.16-0.63), neonatal intensive care admission (relative risk, 0.39; 95% confidence interval, 0.25-0.61), respiratory distress syndrome (relative risk, 0.21; 95% confidence interval, 0.05-0.93), and higher birthweight (mean difference, 435.06 g; 95% confidence interval, 324.59-545.52) with oral progesterone. There was a higher rate of maternal adverse effects with oral progesterone that included dizziness (relative risk, 2.95; 95% confidence interval, 1.47-5.90), somnolence (relative risk, 2.06; 95% confidence interval, 1.29-3.30), and vaginal dryness (relative risk, 2.37; 95% confidence interval, 1.10-5.11); no serious adverse effects were noted. CONCLUSION: Oral progesterone appears to be effective for the prevention of recurrent preterm birth and a reduction in perinatal morbidity and mortality rates in asymptomatic singleton gestations with a history of previous spontaneous preterm birth compared with placebo. There were also increased adverse effects with oral progesterone therapy compared with placebo, although none were serious. Further randomized study on oral progesterone compared with other established therapies for the prevention of recurrent preterm birth are warranted.