The value of oral micronized progesterone in the prevention of recurrent spontaneous preterm birth: a randomized controlled trial.

INTRODUCTION: Progesterone is becoming universally accepted for preventing recurrent spontaneous preterm delivery. There is, however, poor consensus on the effective types and doses of progesterone to be used. Despite the encouraging available research, the role of oral micronized progesterone has not yet been thoroughly investigated. MATERIAL AND METHODS: We randomized 212 singleton pregnancies with past history of spontaneous preterm delivery at <37 weeks, into a progesterone group (receiving 100 mg oral micronized progesterone, six-hourly, starting at 14-18 weeks until 37 weeks or delivery) and an identical placebo group. The rate of spontaneous preterm delivery was the primary outcome. Secondary outcomes included gestational age at birth and admission to neonatal intensive care units. RESULTS: The progesterone group delivered at a later gestational age, and needed longer tocolysis-to-delivery intervals (35.4 weeks vs. 33.9 weeks, p = 0.01, and 87 days vs. 36 days, p < 0.001, respectively). The relative risk of spontaneous preterm delivery was 0.7 (95% confidence interval 0.54-0.92, p = 0.01), and the number needed-to-treat to prevent one case of spontaneous preterm delivery was 5 (95% confidence interval 3-20). The two groups had similar rates of operative delivery and postpartum complications. Progesterone was associated with mild maternal dizziness (29.1% vs. 9.8%, p = 0.002), somnolence (41.6% vs. 19.7%, p = 0.002), and vaginal dryness (20.8% vs. 8.7%, p = 0.03), lower neonatal mortality rates (7.3% vs. 25.2%, p < 0.001), and shorter neonatal intensive care unit admissions (p = 0.008). CONCLUSION: Oral micronized progesterone is effective in preventing spontaneous preterm delivery. The additional advantages of oral administration, affordability, and high safety profile make it worth recommending, at least for further research.

Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus.

AIM: To evaluate glycemic control among women with gestational diabetes mellitus (GDM) under insulin versus metformin (with or without insulin supplementation), and to identify metformin poor responders requiring supplemental insulin. METHODS: In Ain Shams University Hospital, mothers with 26-32-week GDM pregnancies, failing diet control, were randomized to receive metformin (n = 47) or insulin (n = 48). The primary outcome was glycemic control. Secondary outcomes included maternal weight, parameters predicting successful metformin monotherapy, neonatal hypoglycemia, and birthweight. RESULTS: Women using metformin (23.4% needing supplemental insulin) gained less weight (P < 0.001), and had lower fasting glucose during the first and last 2 weeks of treatment (P = 0.014 and 0.008, respectively) when compared with insulin monotherapy. Insulin supplementation in the metformin group was related to initial body mass index, HbA1c, oral glucose tolerance test (GTT), and first week mean glucose level. The 1-h glucose level during initial GTT (Hr1-GTT) and the mean fasting glucose level during the first week of therapy (Wk1-mFG) were the two independent parameters associated with requiring supplemental insulin. Women with Hr1-GTT >212 mg/dL and Wk1-mFG >95 mg/dL had a risk ratio of 58.6 (95%CI: 3.68-933.35, P = 0.004) and 11.5 (95%CI: 2.77-47.34,= 0.0008), respectively for needing supplemental insulin during the course of the study compared with women without. CONCLUSION: Metformin is an effective and safe alternative to insulin in GDM. Women using metformin (± supplemental insulin) had similar glycemic control, less weight gain, and similar rates of side-effects as those on insulin monotherapy. Insulin supplementation to metformin therapy was more likely with elevated Hr1-GTT and Wk1-mFG.

Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial.

AIM: To investigate the effect of chromium picolinate (CrP) on insulin resistance (IR) in polycystic ovary syndrome (PCOS). METHODS: This double blinded randomized controlled trial was conducted in the Gynecology outpatient clinics at Ain Shams University Women's Hospital. Using closed and randomly mixed envelopes, 100 women were selected out of 400 PCOS patients. Eighty-five patients finished the study and were analyzed, 44 in group I and 41 in group II. They were randomly allocated to 6 months of either 1000 µg CrP (50 patients), or placebo capsules (50 patients). Patients were seen monthly to encourage similar diet control and physical exercise plans. The primary outcome was fasting glucose insulin ratio (FGIR), secondary outcomes included ovulation, regularity of the cycle, body mass index (BMI), fasting blood sugar (FBS), fasting serum insulin (FSI), and serum testosterone level. RESULTS: There were no significant differences between women of both groups regarding pretreatment levels of FBS, FSI, FGIR, and serum testosterone. Use of CrP for 6 months was associated with significant reduction of BMI (P < 0.001) and FSI (P = 0.007), and significant rise in FGIR (P = 0.045). CrP significantly increased the chances of ovulation (P = 0.011) and regular menstruation (P = 0.002) by almost twofold after the fifth month of treatment. CONCLUSION: Chromium picolinate is useful in PCOS to reduce IR and stimulate ovulation.

Relation between types of yolk sac abnormalities and early embryonic morphology in first-trimester missed miscarriage.

AIM: The aim of this study was to identify yolk sac (YS) abnormalities and analyze their relation with different embryonic morphologies detected by ultrasonography in first-trimester missed miscarriage. MATERIAL AND METHODS: This descriptive study was carried out on 204 women with established first-trimester missed miscarriage. Ultrasonography depicted the YS's diameter, shape, and echogenicity, as well as the embryonic morphologic findings, including normal shape, isolated defects, and growth disorganization types 1 to 4. The findings were qualified and analyzed. RESULTS: Abnormalities in YS diameter were much more common than those in YS shape or echogenicity. YS with normal diameter constituted 30.9% of the cases, as opposed to a vast majority with normal shape and normal echogenicity (93.5% and 94.7%, respectively). YS of normal diameter, shape and echogenicity were most commonly (47.5%) associated with normal embryonic morphology. Absent YS was most commonly (75%) associated with growth disorganization type 1. Too-small YS were most prevalent among normal embryos (44.8%) and type 1 growth disorganization embryos (27.6%). Cystic YS were mostly associated with isolated embryonic anomalies (36.8%). CONCLUSIONS: This study found a significant relation between YS abnormalities and embryonic morphology in missed miscarriage cases. This was most evident with abnormalities in YS diameter rather than the YS shape or appearance. The commonest combinations met in our cases were growth disorganized 1 embryos with an absent YS, normal embryonic morphology with normal or small YS, and isolated embryonic defects with cystic YS.

Endometrial Progesterone and Estrogen Receptors in Relation to Hormonal Levels in Women with Unexplained Recurrent Miscarriage.

OBJECTIVE: Recurrent miscarriage has been linked to hormonal disturbance due to dysregulation of its receptors rather than to the availability of the hormone. We aimed to investigate endometrial expression of progesterone and estrogen receptors in relation to serum and endometrial hormonal levels in unexplained recurrent miscarriage. METHODS: The present case control study included 20 cases with unexplained recurrent miscarriage and 20 parous women as controls. Ovulation was confirmed using an ovulation kit and 10 to 12 days after detecting the urinary luteinizing hormone surge, all women were subjected to a blood sample and to an endometrial biopsy. Progesterone and estrogen levels were measured in serum and in endometrial tissue and receptor concentrations were in the endometrial sample. RESULTS: Women with recurrent miscarriage showed significantly lower concentration of receptors in both the cytoplasm and the nucleus of endometrial tissue compared with controls. The nuclear/cytoplasm ratio of progesterone receptor was significantly higher in cases compared with controls, implicating that recurrent miscarriage is probably linked to nongenomic activity of the hormone; this was also significant for estrogen receptor. Serum progesterone and estrogen hormonal levels were comparable between groups while both hormones were significantly reduced in the endometrium of recurrent miscarriage cases. Receptors significantly correlated with endometrial hormonal level but not to serum level. CONCLUSION: Recurrent miscarriage might be linked to reduced endometrial progesterone and estrogen receptors and appears to be more related to nongenomic activity of progesterone. Endometrial receptors expression correlates to tissue hormonal level rather than to serum hormonal level.

Antenatal azithromycin to prevent preterm birth in pregnant women with vaginal cerclage: A randomized clinical trial.

Objective: To assess whether antenatal azithromycin given to pregnant women with vaginal cerclage can reduce preterm birth or not. Materials and Methods: We randomized 50 pregnant ladies who underwent cerclage at Ain Shams University Maternity Hospital in group A (receiving 500 mg Azithromycin oral tablets (Zithrokan®, Hikma, Egypt) one tablet orally twice daily for three days in 3 courses at 14th, 24th and 32nd week, plus usual antenatal care) and an identical group B (receiving usual antenatal care). Our primary outcome was gestational age at delivery, and secondary outcomes were birthweight, mode of delivery, and maternal, and perinatal complications. This study was registered on ClinicalTrials.gov with number: NCT04278937. Results: Pregnancy was more prolonged in the Azithromycin group (delivery at 36.8 weeks vs 34.1 weeks; p=0.017). Also, a higher birthweight was observed in the Azithromycin group (2932.6 gm vs 2401.8 gm; p=0.006). No significant difference was found between the two groups as regards to other outcomes (miscarriage, stillbirth, neonatal intensive care unit admission, antepartum hemorrhage, postpartum pyrexia, need for blood transfusion). Conclusion: Adding antenatal azithromycin to women undergoing cerclage prolongs pregnancy and reduces the risk of preterm birth, with a slight increase in birthweight.

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.

Endometrial Progesterone and Estrogen Receptors in Relation to Hormonal Levels in Women with Unexplained Recurrent Miscarriage / Receptores endometriais de progesterona e estrogênio em relação aos níveis hormonais em mulheres com aborto recorrente inexplicável

Abstract Objective Recurrent miscarriage has been linked to hormonal disturbance due to dysregulation of its receptors rather than to the availability of the hormone. We aimed to investigate endometrial expression of progesterone and estrogen receptors in relation to serum and endometrial hormonal levels in unexplained recurrent miscarriage. Methods The present case control study included 20 cases with unexplained recurrent miscarriage and 20 parous women as controls. Ovulation was confirmed using an ovulation kit and 10 to 12 days after detecting the urinary luteinizing hormone surge, all women were subjected to a blood sample and to an endometrial biopsy. Progesterone and estrogen levels were measured in serum and in endometrial tissue and receptor concentrations were in the endometrial sample. Results Women with recurrent miscarriage showed significantly lower concentration of receptors in both the cytoplasm and the nucleus of endometrial tissue compared with controls. The nuclear/cytoplasm ratio of progesterone receptor was significantly higher in cases compared with controls, implicating that recurrent miscarriage is probably linked to nongenomic activity of the hormone; this was also significant for estrogen receptor. Serum progesterone and estrogen hormonal levels were comparable between groups while both hormones were significantly reduced in the endometrium of recurrent miscarriage cases. Receptors significantly correlated with endometrial hormonal level but not to serum level. Conclusion Recurrent miscarriage might be linked to reduced endometrial progesterone and estrogen receptors and appears to be more related to nongenomic activity of progesterone. Endometrial receptors expression correlates to tissue hormonal level rather than to serum hormonal level.

Die-off ratio correlates with increased TNF-α:IL-10 ratio and decreased IVF success rates correctable with humira.

BACKGROUND: Human embryos develop at varying rates in culture, with only a fraction of the eggs retrieved developing to 'transfer quality' embryos. We investigated whether the ratios between the number of eggs retrieved or the number of pro-nucleate embryos formed and the number of Day 3 embryos with ≥5 cells [oocyte 'die-off ratios' (DOR)] were correlated with the chance of IVF success, independent of other factors such as embryo grade score and patient's age. We also investigated what factors may be correlated with this ratio. METHODS: 608 IVF fresh cycles in subfertile women were retrospectively evaluated. For each cycle, an oocyte DOR number was calculated as follows: Number of eggs retrieved divided by the number of Day 3 embryos with ≥5 cells. This number was correlated with the subsequent success rates for the index cycles. A 'post-fertilization' or 'embryo' die-off ratio (EDOR; the number of pro-nucleate embryos/the number of day 3 embryos ≥5 cells) was also calculated. RESULTS: The oocyte DOR showed a reverse linear correlation with IVF live birth rate. Live birth rate = (-5.75; DOR) +71.6 (with DOR > 1; P ≤ 0.005; R = -0.87). In addition, the oocyte DOR continued to show an inverse correlation with success rates even when embryo quality and patient's age were held constant. The post-fertilization or EDOR also continued to show a statistically significant negative correlation with live birth rate (R = -0.91; P ≤ 0.01). The preconception TNF-α:IL-10 ratio, an immmunologic marker (drawn 3.3 ± 2.6 months preconception), was more strongly correlated with high oocyte DOR than either age or number of eggs retrieved (P = 0.04, 0.14, 0.72, respectively). When anti-TNF-α therapy (Humira) was given preconception, the oocyte DOR's negative effect on live birth rate was nearly eliminated (correlation coefficient between oocyte DOR and live birth rate: cycles using no Humira, R = -0.90, P ≤ 0.006; cycles using Humira, R = 0.25, P ≤ 0.55). CONCLUSIONS: In subfertile women undergoing IVF, the oocyte DOR may help predict IVF success rates. This factor may offer an additional tool to help improve implantation rate, clinical pregnancy rate, live birth rate, and live birth rate per embryo transferred for an upcoming IVF cycle. Although many mechanisms may contribute to the oocyte DOR's negative effect on IVF success rates, its correlation with elevated preconception TNF-α:IL-10 ratio and correction with Humira suggests a strong immunologic component that may be treatable.

Elevated preconception CD56+ 16+ and/or Th1:Th2 levels predict benefit from IVIG therapy in subfertile women undergoing IVF.

PROBLEM: We sought to answer two questions: First, is there a group of patients who benefit from intravenous immunoglobulin (IVIG) in IVF? Second can this group of patients be identified by preconception blood testing? METHOD OF STUDY: A total of 202 IVF cycles in subfertile women were divided into four groups. Group I: 62 cycles with preconception Th1:Th2 ratio and/or % CD56(+) cell elevation using IVIG; Group II: 27 cycles with similar Th1:Th2 and/or % CD56(+) cell elevation not using IVIG; Group III: 71 cycles with normal Th1:Th2 and/or % CD56(+) cell levels using IVIG; Group IV: 42 cycles with normal Th1:Th2 and % CD56(+) levels not using IVIG. These groups were similar with regard to patient age, diagnosis, and past failure history. RESULTS: The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred per cycle) was 45% (55/123), 22% (12/54), 54% (75/139), and 48% (40/84) for Groups I-IV, respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 61% (38/62), 26% (7/27), 69% (49/71), and 71% (30/42), respectively. The live birth rate was 58% (36/62), 22% (6/27), 61% (43/71), and 71% (30/42), respectively, and the live birth per embryo transferred was 40% (49/123), 13% (7/24), 43% (60/139), and 48% (40/84), respectively. There was a significant improvement in implantation, clinical pregnancy, live birth rate and live birth rate per embryo transferred for Group I versus Group II (P = 0.0032, 0.0021, 0.0017, and 0.0002, respectively) and for Group II versus Group IV (P = 0.0021, 0.0002, <0.0001 and <0.0001, respectively). There was no significant difference in success rates between Groups I and III (P = 0.085, 0.23, 0.45, 0.34, respectively) and between Groups III and IV (P = 0.22, 0.48, 0.17, 0.31, respectively). CONCLUSION: In subfertile women with preconception Th1:Th2 and/or % CD56(+) cell elevation, IVF success rates are low without IVIG therapy but significantly improve with IVIG therapy. In patients with normal Th1:Th2 and normal CD56(+) cell levels, IVF success rates were not further improved with IVIG therapy. IVIG may be a useful treatment option for patients with previous IVF failure and preconception Th1:Th2 and/or NK elevation. Preconception immune testing may be a critical tool for determining which patients will benefit from IVIG therapy. Prospective controlled studies (preferably double-blind, stratified, and randomized) are needed for confirmation.

Birth defect rates in women using Adalimumab (Humira(®) ) to treat immunologic-based infertility in IVF patients.

PROBLEM: This study compares the birth defect rate in women using preconception TNF-α inhibitor (Adalimumab) during an in vitro fertilization (IVF) cycle to a similar population of women not using these immunologic therapies. METHOD OF STUDY: One hundred subfertile women aged ≤38years experienced ongoing pregnancies of which 36 resulted in twin pregnancies (136 babies). These successful cycles were divided into two different treatment groups: group I comprised 31 cycles (23 ICSI) using preconception Adalimumab (Humira) with or without pre- or post-conception intravenous immunoglobulin (IVIG) (last dose of Humira given 65.3±41.5days before embryo transfer). Group II comprised 69 cycles (58 ICSI) with no exposure to Humira or IVIG. Group I included all eligible fresh cycles containing at least five 5-celled embryos on day 3. Group II had similar entry criteria, but eligible cycles were randomly selected owing to a larger population size. Patients were later contacted by the clinic for neonatal health information. RESULTS: Delivery outcomes were as follows: group I experienced one case of DiGeorge syndrome (chromosome 22 deletion) that was electively terminated out of 41 babies (10 sets of twins) delivered. Group II experienced one case of neonatal heart defect and another case of Edward's syndrome (Trisomy 18) out of 95 babies (26 sets of twins) delivered. The anomaly rate was 2.44% (1/41) and 2.11% (2/95) for groups I and II, respectively, comparable to the expected birth defect rate for the normal IVF population. CONCLUSION: Preconception TNF-α inhibitor does not appear to increase the birth defect rate in women undergoing IVF. A larger, clinical trial with blinded delivery assessment is needed to confirm these safety conclusions.

Degree of TNF-α/IL-10 cytokine elevation correlates with IVF success rates in women undergoing treatment with Adalimumab (Humira) and IVIG.

PROBLEM: In this retrospective observational study, we investigate whether the degree of preconception cytokine elevation predicts the risk of IVF failure. METHOD OF STUDY: Seventy-six women undergoing fresh IVF/ICSI cycles (≤41 years, good responders with ≥5 embryos on day 3, each with ≥5 cells with a normal endometrium) and preconception tumor necrosis factor (TNF)-α/IL-10 cytokine elevation [PMA/ionomycin stimulated CD3(+) CD8(-) ; TNF-α/IL-10 ratio above 30.6 (normal range 13.2-30.6)] were retrospectively evaluated. This high cytokine population was divided into two subgroups. Group I included 39 women with severe preconception and pre-treatment TNF-α/IL-10 cytokine elevation >39.0 (mean 47.5 ± 7.5 pre-treatment, mean 31.5 ± 9.4 post-treatment) treated with preconception Adalimumab (Humira(®) ) and intravenous immunoglobulin (IVIG). Group II included 37 women with a moderate TNF-α/IL-10 ratio >30.6 and ≤39.0 (mean 35.2 ± 2.2 pre-treatment, mean 28.8 ± 8.5 post-treatment) treated with preconception Adalimumab and IVIG. Groups I and II were comparable in relation to baseline IVF characteristics and patient history. RESULTS: The implantation rate (number of gestational sacs per embryo transfer, with an average of two embryos transferred per cycle) was 43% (36/83) for Group I and 56% (44/78) for Group II. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 67% (26/39) for Group I and 73% (27/37) for Group II. The delivery rate was 56% (22/39) for Group I and 68% (25/37) for Group II. The live birthrate per embryo transferred was 36% (30/83) for Group I and 45% (35/78) for Group II. Comparing Groups I and II, there was non-significant increase in implantation rate, clinical pregnancy rate, delivery rate, and live birthrate per embryo transferred (P = 0.1, 0.6, 0.4, and 0.3, respectively). However, when the subgroup with the least optimal cytokine conditions (Group I with inadequate cytokine suppression) was compared to the subgroup with the most optimal cytokine conditions (Group II with adequate cytokine suppression), the increase in implantation rate reached statistical significance [41% (19/46) to 64% (29/45); P = 0.04]. The reduction in TNF-α/IL-10 ratio following immunotherapy was highly significant (P < 0.0001). CONCLUSION: The degree of preconception TNF/IL-10 elevation may correlate with an increased risk of IVF failure. Elevated TNF-α/IL-10 ratios can be corrected with therapy. It may be possible to improve IVF success rates by modulating high cytokine levels. Although our pilot database is small, the trends in the data are consistent and compelling. Larger studies are needed for confirmation.

Treatment with adalimumab (Humira) and intravenous immunoglobulin improves pregnancy rates in women undergoing IVF.

PROBLEM: The purpose of this study was to investigate whether treatment with TNF-alpha inhibitors and/or intravenous immunoglobulin (IVIG) increases in vitro fertilization (IVF) success rates among young (<38 years) women with infertility and T helper 1/T helper 2 cytokine elevation. METHOD OF STUDY: Seventy-five sub-fertile women with Th1/Th2 cytokine elevation were divided into four groups: Group I: Forty-one patients using both IVIG and Adalimumab (Humira), Group II: Twenty-three patients using IVIG, Group III: Six patients using Humira, and Group IV: Five patients using no IVIG or Humira. RESULTS: The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred by cycle) was 59% (50/85), 47% (21/45), 31% (4/13) and 0% (0/9) for groups I, II, III and IV respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 80% (33/41), 57% (13/23), 50% (3/6) and 0% (0/5) and the live birth rate was 73% (30/41), 52% (12/23), 50% (3/6) and 0% (0/5) respectively. There was a significant improvement in implantation, clinical pregnancy and live birth rates for group I versus group IV (P = 0.0007, 0.0009, and 0.003, respectively) and for group II versus group IV (P = 0.009, 0.04 and 0.05, respectively). CONCLUSION: The use of a TNF-alpha inhibitor and IVIG significantly improves IVF outcome in young infertile women with Th1/Th2 cytokine elevation.