Pro-inflammatory and anti-inflammatory cytokine profiles in fetal growth restriction.

The purpose of this investigation was to measure cytokine production by maternal peripheral blood lymphocytes from women with intrauterine growth restriction (IUGR) and from healthy pregnant women, and to investigate the relationship between cytokine profiles and IUGR. Thirty-six women with IUGR and 22 control healthy pregnant women with normal fetal growth were studied. Levels of pro-inflammatory cytokines (IFNy, TNFa, IL-8, IL-12, IL-18, IL-23) and anti-inflammatory cytokines (IL-4, IL- 10, IL-13) produced by mitogen-stimulated peripheral blood mononuclear cells were measured by ELISA. Levels of the anti-inflammatory cytokine IL-4 were higher in normal pregnancy compared to IUGR, indicating an anti-inflammatory bias. Levels of the pro-inflammatory cytokines IL-6, TNFα, and IL-12 were significantly higher and levels of the anti-inflammatory cytokine IL- 10 lower in IUGR with placental insufficiency than in IUGR without placental insufficiency, suggesting a stronger pro-inflammatory bias in IUGR with placental insufficiency. Ratios of pro- to anti-inflammatory cytokines suggest a dominance of pro-inflammatory cytokines. The authors conclude that an increased pro-inflammatory cytokine bias is observed in IUGR compared to normal pregnancy, and an increased pro-inflammatory cytokine dominance is seen in IUGR with placental insufficiency compared to IUGR without placental insufficiency.

Elevated progesterone during ovarian stimulation for IVF.

There is an ongoing debate regarding the impact of premature progesterone rise on the IVF outcome. The objective of this review is to assess evidence of poorer ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end of follicular phase in ovarian stimulation. It also explores the origin of the progesterone rise, potential modifying factors and possible methods to prevent its rise during ovarian stimulation. This review draws on information already published from monitoring progesterone concentrations at the end of follicular phase in ovarian stimulation. The databases of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of the follicular phase in ovarian stimulation. Future trials should document the cause and origin of premature progesterone in stimulated IVF cycles. There is an ongoing debate regarding the impact of premature progesterone rise on the IVF outcome. The objective of this review is to assess evidence of poorer ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end of follicular phase in ovarian stimulation. It also explores the origin of the progesterone rise, potential modifying factors and possible methods to prevent its rise during ovarian stimulation. This review draws on information already published from monitoring progesterone concentrations at the end of follicular phase in ovarian stimulation. The databases of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of follicular phase in ovarian stimulation. Future trials should document the cause and origin of premature progesterone in stimulated IVF cycles.

The relationship of premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/recombinant FSH-stimulated cycles.

OBJECTIVE(S): To investigate the relationship between premature progesterone (P) rise and serum estradiol (E(2)) levels and the number of follicles in GnRH antagonist/rec-FSH stimulated cycles. STUDY DESIGN: Two hundred and seven patients treated by IVF/ICSI at the Centre for Reproductive Medicine of the Dutch-Speaking Brussels Free University were included in this observational study. They received 200 IU/day rec-FSH from day 2 of the cycle and daily GnRH antagonist starting on day 6 of stimulation. The criteria for hCG administration included the presence of ≥3 follicles of ≥17 mm diameter. Serum P, E(2) and LH were determined on the day of hCG administration. The outcome measure was to identify a threshold of E(2) and number of follicles on the day of hCG administration which would define a progesterone rise on the day of hCG administration (cut-off value of 1.5 ng/ml). RESULT(S): Patients with a P >1.5 ng/ml had significantly higher concentrations of E(2) and increased number of follicles on the day of hCG administration compared to those with P ≤1.5 ng/ml. However, patients with a P >1.5 ng/ml the day of hCG showed lower pregnancy rates than those with P <1.5 ng/ml (17.8 vs. 32.7%, respectively; p<0.05). A ROC curve was employed in order to estimate a cut-off for E(2) on day of hCG >1790.5 pg/ml and more than 9.5 follicles of ≥11 mm in diameter for progesterone rise over 1.5 ng/ml. CONCLUSION(S): A significant impact is shown on progesterone rise by E(2) and number of follicles on the day of hCG administration in GnRH antagonist/rec-FSH-stimulated cycles. With this knowledge, an upcoming progesterone rise during follicular phase can be anticipated and prevented.

Butyrylcholinesterase activity in women with diabetes mellitus in pregnancy: correlation with antioxidant activity.

A total of: 25 women with gestational diabetes, 25 with type 2 diabetes, 21 with healthy pregnancies and 15 non-pregnant healthy controls were investigated to evaluate the relationship between butyrylcholinesterase activity and antioxidant status in the serum and placenta of diabetic pregnant women. Levels of antioxidant activities were estimated by Randox Kits and malondialdehyde and butyrylcholinesterase by colorimetric methods. Butyrylcholinesterase activity was elevated in the serum and placenta in normal pregnancy vs diabetic cohorts (p < 0.01) and there was a higher activity level in gestational and type 2 diabetes on insulin (p < 0.05) compared with diet controlled. There was higher malondialdehyde and lower antioxidant activity in diet vs insulin controlled diabetes (p < 0.01). Serum and placental butyrylcholinesterase activity showed a strong inverse correlation with malondialdehyde (r = -0.876, p < 0.001) and (r = 0.542, p < 0.01), but strong positive correlation with total antioxidant activity in serum (r = 0.764, p < 0.001) and placenta (r = 0.642, p < 0.01). Butyrylcholinesterase may therefore, be involved in reducing oxidative stress in diabetic pregnancy.

Factors contributing to gender differences in serum retinol and alpha-tocopherol in infertile couples.

Oxidative stress is detrimental to fertility potential. Retinol and alpha-tocopherol are natural antioxidants that inhibit lipid peroxidation and protect against cell damage induced by oxidative stress. This study evaluated whether gender-related differences in antioxidant status exist among couples with infertility and, if so, to evaluate relevant factors that may contribute to such differences. Retinol and alpha-tocopherol in the sera of 40 couples and in the semen of 40 men were measured using high performance liquid chromatography. Serum retinol and alpha-tocopherol in women were significantly higher than in men (both P < 0.001). There was an inverse relationship between body mass index and serum retinol and alpha-tocopherol in both men and women. Heavy smokers (>or=20 cigarettes/day), compared with nonsmokers, had lower serum concentrations of retinol and alpha-tocopherol. Serum concentrations of retinol and alpha-tocopherol in men with normal sperm parameters were significantly higher than in those with oligozoospermia and asthenozoospermia (both P < 0.001). Lower serum retinol and alpha-tocopherol in men compared with their female partners could be related to their older age, higher body mass index and smoking habits. Low concentrations of these natural antioxidants were associated with abnormal semen parameters in men and anovulation in women.

Immediate and delayed add-back hormonal replacement therapy during ultra long GnRH agonist treatment of chronic cyclical pelvic pain.

OBJECTIVE: To assess the safety and efficacy of long-term use of long-acting GnRH agonist in women with chronic cyclical pelvic pain using immediate versus delayed add-back hormonal replacement therapy (HRT). DESIGN: A prospective randomised trial. SETTING: Reproductive and Developmental Medicine, Academic Unit, University Teaching Hospital and NHS Hospitals. POPULATION: Thirty-eight premenopausal women with chronic cyclical pelvic pain were recruited. METHODS: Women were given Zoladex 10.8 mg over 18 months and randomised to receive HRT (tibolone 2.5 mg) either immediately or after 6 months. Follow up was 12-month post-treatment. MAIN OUTCOME MEASURES: Bone mineral density at 6 months, the end of treatment (18 months), and 12 months later, pain and quality of life. RESULTS: Women treated with immediate HRT add-back showed less bone mineral density loss at 6 months and less vasomotor symptoms compared with those who had delayed HRT add-back treatment. Long-term follow up showed both groups experienced equivalent bone mineral density loss. Pain and health-related quality-of-life assessment showed improvement in both groups but there was evidence of a return to baseline levels after ending treatment. CONCLUSION: Long-term use of GnRH agonist plus immediate add-back HRT is a safe and acceptable approach to intractable cyclical pelvic pain. Given the delay in reactivation of the hypothalamo-pituitary-ovarian axis after long-term suppression, an intermittent dose regime with GnRH agonist might warrant investigation.

The expression of MUC1 in human Fallopian tube during the menstrual cycle and in ectopic pregnancy.

BACKGROUND: Ectopic pregnancy is a major cause of maternal morbidity and mortality with increasing incidence worldwide. We have investigated whether epithelia from Fallopian tubes (FTs) bearing an ectopic pregnancy differ from normal tubes in expression of MUC1. METHODS: Since it is not possible to collect FTs from women carrying a healthy pregnancy, we studied tissue collected at the time of hysterectomy for benign disease. Women were injected with hCG in the days leading up to hysterectomy, and pseudopregnancy confirmed by the presence of high serum progesterone levels and the decidualization of the endometrium. FTs from the different stages of the menstrual cycle (n = 24), tubes bearing an ectopic pregnancy (n = 15) and pseudo-pregnant tubes (n = 6) were collected and examined using immunohistochemistry and quantitative RT-PCR. RESULTS: MUC1 was present at the apical surface of the tubal epithelial cells throughout the menstrual cycle, but intracellular localization was minimal in the follicular phase, increasing to a maximum in the luteal phase. MUC1, including the glycoform recognized by antibody 214D4, was found at the apical surface of tubal epithelium in both the ectopic and pseudo-pregnant groups and the intracellular expression was much stronger in the pseudo-pregnant group than in the ectopic group. The 214D4 epitope was absent from tubal tissue adjacent to ectopic implants. CONCLUSIONS: The decrease in MUC1 expression and altered glycosylation in tubal epithelium from ectopic pregnancy may reflect an increase in receptivity.

Progesterone-induced blocking factor (PIBF) modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery.

Spontaneous miscarriage and preterm delivery are common complications of pregnancy. Pro-inflammatory cytokines have been shown to be associated with recurrent spontaneous miscarriage (RSM) and preterm delivery (PTD) and these have led to exploration of ways to downregulate pro-inflammatory cytokines and/or to upregulate anti-inflammatory cytokines. Progesterone-induced blocking factor (PIBF) is a molecule with inhibitory effects on cell-mediated immune reactions. We have ascertained the effects of PIBF on secretion of selected type 1 and type 2 cytokines by peripheral blood mononuclear cells from healthy non-pregnant women, women undergoing normal pregnancy, women with unexplained RSM and women with PTD. Peripheral blood mononuclear cells from 30 women with a history of unexplained RSM, 18 women undergoing PTD, 11 women with normal pregnancy and 13 non-pregnant healthy women were stimulated with a mitogen in the absence and presence of PIBF after which the levels of cytokines released into culture supernatants were determined by ELISA. Production of the type 2 cytokines IL-4, IL-6 and IL-10 by lymphocytes from the RSM and PTD groups and of IL-4 and IL-10 by lymphocytes from healthy pregnant women was significantly increased upon exposure to PIBF, while the levels of type 1 cytokines were not affected. Ratios of type 1:type 2 cytokines were decreased, suggesting a shift towards Th2 bias. PIBF did not affect cytokine production by lymphocytes from non-pregnant women. Thus, PIBF acts on lymphocytes in pregnancy to induce a type 1 to type 2 cytokine shift by upregulating the production of type 2 cytokines.

Indications of the mechanisms involved in improved sperm parameters by zinc therapy.

OBJECTIVE: To determine possible indications of the mechanisms involved in improved sperm parameters by zinc therapy in asthenozoospermic men. SUBJECTS AND METHODS: Forty-five men with asthenozoospermia (>or=40% immotile sperm) were randomized into four therapy groups: zinc only: n = 11; zinc + vitamin E: n = 12 and zinc + vitamins E + C: n = 14 for 3 months, and non-therapy control group: n = 8. Semen analysis was done according to WHO guidelines. Malone dialdehyde, tumour necrosis factor-alpha (TNF-alpha), total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase were determined in the semen and serum. Antisperm antibodies IgG, IgM and IgA were evaluated by immunobeads. Sperm chromatin integrity was determined by acid denaturation by acridine orange and sperm apoptosis by light and electron microscopy. The effect of zinc on in vitro induced sperm oxidative stress by NADH was evaluated. RESULTS: Asthenozoospermia was significantly associated with oxidative stress with higher seminal malone dialdehyde (8.8 vs. 1.8 mmol/l, p < 0.001) and TNF-alpha (60 vs. 12 pg/l, p < 0.001), and low total antioxidant capacity (1.8 vs. 8.4, p < 0.01), SOD (0.8 vs. 3.1, p < 0.01) and glutathione peroxidase (1.6 vs. 4.2, p < 0.05), compared to normozoospermia. Zinc therapy alone, in combination with vitamin E or with vitamin E + C were associated with comparably improved sperm parameters with less oxidative stress, sperm apoptosis and sperm DNA fragmentation index (DFI). On the whole, there was no difference in the outcome measures between zinc only and zinc with vitamin E and combination of vitamins E + C. In the in vitro experiment zinc supplementation resulted in significantly lower DFI (14-29%, p < 0.05) compared to zinc deficiency. CONCLUSION: Zinc therapy reduces asthenozoospermia through several mechanisms such as prevention of oxidative stress, apoptosis and sperm DNA fragmentation.

Prevalence of endometrial proliferation in pipelle biopsies in tamoxifen-treated postmenopausal women with breast cancer in Kuwait.

OBJECTIVE: To determine the prevalence of pathologic changes in the endometrium of tamoxifen-treated asymptomatic postmenopausal patients with breast cancer. SUBJECTS AND METHODS: Fifty postmenopausal asymptomatic breast cancer patients with positive estrogen receptor status were treated with 20 mg of tamoxifen daily for a period of 5-60 months. The control group consisted of 30 asymptomatic postmenopausal breast cancer patients who were negative for estrogen receptor and therefore did not receive tamoxifen. Endometrial biopsies were performed using Pipelle endometrial suction curette at least 5 months after the study began. The endometrium was classified as atrophic (negative finding) and proliferative or hyperplastic (positive findings). The study and control groups were compared for demographic characteristics, risk factors for endometrial cancer, histological findings and the duration of tamoxifen treatment. RESULTS: A significantly greater prevalence of endometrial abnormalities existed among the tamoxifen-treated than control patients (76 vs. 33%, p < 0.001). The abnormal endometrial changes were further demarcated in both groups into proliferative (54 vs. 26.7%, p = 0.02) and hyperplastic (22 vs. 6.6%, p = NS). In the study group, 63.6% of hyperplastic endometrium was simple hyperplasia and 36.4% was complex/no atypia hyperplasia, while in the control group all the cases were simple hyperplasia. No endometrial cancer was detected in either group. In addition, there was a positive association between the duration of tamoxifen exposure (<1 year vs. >/=1 year) and the endometrial abnormalities (46.6 vs. 88.6%, p = 0.003; proliferative 57.1 vs. 74.1%, p = 0.015; hyperplastic 42.8 vs. 25.8%, p = NS). CONCLUSION: The adjuvant use of tamoxifen is associated with significant time-dependent abnormal endometrial changes among patients with cancer of the breast.

Changing trends in the obstetric indications for cervical cerclage.

Cervical incompetence causes repeated mid-trimester miscarriage and preterm delivery with high fetal wastage. Since the introduction of cervical cerclage in 1951, it has undergone many changes with regard to the techniques, indications and postoperative care. The objective of this study is to review the changing trends in the current indications of cervical cerclage and subsequent perinatal outcome at the maternity hospital from January 1992 to December 1999. All the files of women who had had cervical cerclage were evaluated in terms of characteristics of the women, indications and obstetric outcome after cervical cerclage. Of 65539 who delivered in the hospital, 1021 women had had cervical cerclage, giving an incidence of 1.21%. There was a significant increase in the incidence of cervical cerclage, from 1.13% in 1992 to 1.40% in 1999 (P < 0.01). More women with multiple pregnancy in 1996 - 99 had cerclage than in 1992 - 94 period [22.7 vs. 8.5% (P < 0.01)]. It is clear that more cervical sutures are being performed in multiple pregnancies arising from assisted reproductive technology as well as after ultrasonographic evidence of cervical dilatation. A multicentre randomised clinical trial is therefore advocated to evaluate its effectiveness in these cases.

Pro-inflammatory maternal cytokine profile in preterm delivery.

PROBLEM: The objective of this study was to determine the levels of cytokines produced by maternal peripheral blood mononuclear cells (PBMC) upon stimulation with a mitogen, with autologous placental cells and with a trophoblast antigen extract. METHOD OF STUDY: Peripheral blood mononuclear cells from 54 women with a history of successful pregnancy and 30 women undergoing preterm delivery (PTD) were stimulated with the mitogen and antigens, and the cytokine levels in mitogen-stimulated culture supernatants assessed. RESULTS: Significantly higher levels of the type 1 cytokines, interferon (IFN)-gamma and interleukin (IL)-2, were produced by the PTD group than by the normal pregnancy group, which on the contrary showed significantly greater production of the type 2 cytokines, IL-4, IL-5 and IL-10. A comparison of the ratios of type 2 to type 1 cytokines is indicative of a type 1 cytokine bias in PTD. CONCLUSIONS: These data are suggestive of a maternal type 1 cytokine bias in PTD.

Suppression of Na+-H+ exchanger-1 in placentas of type 2 diabetic pregnant women: possible functional implication.

Placental Na(+)/H(+) exchanger (NHE-1), which plays an important role in maintaining fetal and maternal Na+ and H+ homeostasis, is uniquely regulated. However, the role of this protein in type-2 diabetic placentas, and the molecular basis for its unique regulation in normal placenta remain poorly understood. To address these issues, a C-terminus regulatory domain of NHE-1 was cloned and sequenced from normal human placentas, and was used to prepare a GST-fusion protein for raising polyclonal antibodies. For this study, age-matched type 2 diabetic (n=8) and normal (n=8) pregnant women were recruited to investigate the effects of controlled hyperglycemia on the expression of placental NHE-1 at term delivery. The C-terminal sequence in the normal human placental isoform was identical to that reported for other tissues. The antibodies reacted selectively with a 110 kD protein. The level of NHE-1 protein was decreased significantly ( p<0.05) in diabetic placentas, whereas beta-actin, an internal control, remained unaltered. Yield of placental crude microsomes was significantly higher from diabetic placentas. Interestingly, the levels of NHE-1 mRNA and beta-actin mRNA did not change in diabetic pregnancies. Blood pressure values of the mothers in both groups were also normal. The placental mass and weight of babies were slightly increased, whereas the gestational age was lower in diabetic pregnancies. These results suggest that the unique regulation of placental NHE-1 is not due to differences in its C-terminus structure. Lack of a significant correlation between the suppression of NHE-1 and gestational age, placental mass or birth weight in the diabetic pregnancies suggests that suppression is independent of these parameters, and is regulated post-transcriptionally. This change in NHE-1 may contribute to an adequate provision of electrolytes and nutrients to the fetus.

Effect of increased glucose load on maternal-fetal transport of alpha-aminoisobutyric acid in the perfused human placenta: in vitro study.

The role of hyperglycemia on modulation of maternal-fetal transport of amino acids in humans is little understood. Hence, we have explored the effect of increased glucose load on transport kinetics of a model non-metabolizable amino acid, alpha-aminoisobutyric acid (AIB), in the human placenta in vitro. Transport kinetics of AIB in maternal-fetal direction was studied using perfusion of isolated human placental lobules. NCTC (National Culture and Tissue Collection)-135 medium, diluted with Earle's buffered salt solution was used as the perfusate and tritiated water was used as the reference marker. Effect of increased glucose load on transport kinetics of study and reference substances was studied in normal term placentae (n=5; gestational age, 38.5 +/- 0.5 weeks) in succeeding experimental phases, after a control perfusion phase with physiological glucose concentration. AIB transport fraction (TF), relative to tritiated water TF, averaged 54.8% in control euglycemic phase while in hyperglycemic concentration phases of 27.8 and 55.6 mM, the AIB TF index averaged 42.4% and 38.2%, respectively. Analysis of variance revealed that the difference was statistically significant. Similarly, absorption rate index of the amino acid was also significantly lower in the hyperglycemic perfusion phases compared to control euglycemic phase. We conclude that hyperglycemia may play a deleterious role in limiting maternal-fetal transport of A-type amino acids in the in vivo state.

A favorable outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome.

OBJECTIVE: To study the outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome treated with the standard treatment regimes including intravenous immunoglobulin (IV Ig). METHODS: Forty three patients with recurrent pregnancy loss associated with antiphospholipid syndrome diagnosed before pregnancy and subdivided into primary (18) and secondary (25) subgroups were closely monitored all through pregnancy with serial blood tests and ultrasonography until the pregnancy ended in miscarriage or delivery. The patients were treated with low-dose aspirin and heparin and or steroids and IV Ig given to some selected patients. The maternal and fetal outcomes were analysed. RESULTS: The mean age of the patients in the primary subgroup (24.60 +/- 4.30) years was significantly lower than the mean age of the secondary recurrent pregnancy loss group (31.50 +/- 4.50) years, (p < 0.0001). 85.00% of all the previous miscarriages were in the first trimester. There was no significant difference in the incidence of live births in the primary (77.80%) and secondary (84.00%) groups, (p > 0.05); the babies were of normal birth weight. The incidence of caesarean section in the primary and secondary groups, 22.23% and 12.00% respectively, were not significantly different (p > 0.05). Intravenous immunoglobulin added to the standard therapy resulted in 100% live births. Maternal complications were negligible. CONCLUSIONS: The fetal and maternal outcome of pregnancies in patients with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome were virtually identical and quite satisfactory. Intravenous immunoglobulin added to the standard therapy resulted in excellent fetal and maternal outcome, although its definitive role will have to wait for the outcome of randomised trials.

The Harderian gland of the Cheesman's gerbil (Gerbillus cheesmani ) of the Kuwaiti desert.

The Harderian gland is a large orbital structure. Several functions have been ascribed to the gland such as lubrication of the eye, a source of pheromones, thermoregulartory lipids and photoprotective secretions and a part of the retinal-pineal axis. In the present study, the Harderian gland of the Cheesman's gerbil, Gerbillus cheesmani, is described for the first time. The gland is located around the posterior portion of the eyeball. The gland is compound tubular, surrounded by a thin connective tissue capsule. Only one secretory epithelial cell type was recognized, characterized by the presence of lipid vacuoles and cytoplasmic slashes in high numbers; the former being more concentrated towards the apical part while the latter being more concentrated towards the central and basal parts. Some of the cytoplasmic slashes contained electron dense filamentous structures. Similar structures were observed in the lipid vacuoles. Thus, a functional relationship between the cytoplasmic slashes and the lipid vacuoles is suggested. A unique structure was observed, termed dome-like cells, located between the epithelial cells and the basement membrane. These cells were characterized by the extensive presence of pleomorphic mitochondria and compact lamellae of granular endoplasmic reticulum (GER) in the form of finger prints. The gland was found to be actively secreting porphyrins as well as lipids. Cellular debris was also seen in the tubular lumina. Myoepithelial cells with their spindle shape and elongated nuclei were evident between the basement membrane and the secretory epithelium. Sparse interstitial tissue was observed in-between the gland tubules of both male and female gerbils. Macrophages, dendritic melanocytes and lymphocytes are the most represented cellular components of the interstitium. Further studies are required to investigate the function of the dome-like cells as well as the role of lymphocytes in the rodents Harderian gland.

Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis.

In-vitro fertilization (IVF) is an effective infertility treatment for women with endometriosis, but most women need to undergo several cycles of treatment to become pregnant. This case-control study was designed to assess how consistently women with ovarian endometriosis respond to ovarian stimulation in consecutive treatment cycles compared to women with tubal infertility. We compared outcome measures in 40 women with a history of surgically confirmed ovarian endometriosis and 80 women with tubal infertility, all of whom had at least three IVF treatment cycles. The groups were matched for age and early follicular follicle stimulating hormone (FSH) concentration at their first IVF cycle. Outcome measures included number of follicles, number of oocytes, peak oestradiol concentration and number of FSH ampoules required per follicle. Cumulative pregnancy and live birth rates were calculated in both groups. The ovarian endometriosis group had a significantly poorer ovarian response and required significantly more ampoules of FSH per cycle, a difference that became greater with each subsequent cycle. However, cumulative pregnancy (63.3 versus 62.6% by fifth cycle) and live birth (46.8 versus 50.9% by fifth cycle) rates were similar in both groups. In conclusion, despite decreased ovarian response to FSH, ovarian endometriosis does not decrease the chances of successful IVF treatment.

Mitogen-induced cytokine responses of maternal peripheral blood lymphocytes indicate a differential Th-type bias in normal pregnancy and pregnancy failure.

PROBLEM: Profiles of Th1- and Th2-type cytokines were studied in women with a history of successful pregnancy and in women with a history of unexplained recurrent spontaneous abortions (RSA) with the objective of elucidating Th1- and Th2-type bias in normal pregnancy and pregnancy failure. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMCs) from 54 women with a history of normal pregnancy and 23 women with a history of unexplained RSA, obtained at delivery or on the day of abortion, respectively, were stimulated with phytohemagglutinin (PHA), followed by the estimation of four Th2 cytokines and four Th1 cytokines. RESULTS: Significantly greater levels of Th2 cytokines were produced by the normal group than by the RSA group. On the other hand, significantly higher levels of Th1 cytokines were produced by the RSA group than by the normal pregnancy group. CONCLUSIONS: These data support the concept that unexplained recurrent spontaneous abortion is associated with an increase in Th1-type reactivity, while Th2 dominance is a feature of successful pregnancy.

Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions.

Spontaneous abortion is the most common complication of pregnancy, but the etiology of a significant proportion of abortions is still unknown. We have examined the production of Th1- and Th2-type cytokines by women with unexplained recurrent spontaneous abortion (RSA) since it appears that successful murine pregnancy occurs in a Th2-dominant situation and that Th1-type immunity is associated with pregnancy failure. We have compared maternal reactivity toward placental antigens in women with a history of successful pregnancy with that in women with a history of RSA. This was done by coculturing maternal peripheral blood mononuclear cells (PBMC) with autologous placental cells and also by stimulating maternal PBMC with antigens from a choriocarcinoma cell line of trophoblastic origin. We detected significantly greater levels of the Th2 cytokines IL-6 and IL-10 in normal pregnancy compared to unexplained RSA and significantly higher levels of the Th1 cytokine IFN-gamma in RSA compared to normal pregnancy. These results suggest that women with normal pregnancy have a higher Th2 bias, while women with a history of RSA evince a bias toward Th1-type reactivity.