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Purpose: Gonadotropin-resistant ovary syndrome (GROS) is a rare endocrine disorder that causes hypergonadotropic hypogonadism, amenorrhea, and infertility. This study reports live birth in two women with GROS who underwent fertility treatment with in vitro maturation (IVM)., Methods: Both patients had primary infertility, amenorrhea (primary and secondary), typical secondary sexual characters, elevated gonadotropin levels, normal ovarian reserve, normal chromosomal characteristics, and previous nonresponsiveness gonadotropin stimulations. One patient had polymorphism of the follicle-stimulating hormone receptor, which is a predictor of poor ovarian response. Given unresponsiveness to exogenous gonadotropin stimulations, IVM with human chorionic gonadotropin priming (hCG-IVM) was performed in both patients. All transferrable embryos were vitrified., Results: Both patients achieved pregnancy after their first frozen embryos transfer, and each delivered a healthy baby boy., Conclusions: These results suggest that IVM should be a first-line therapeutic option for patients with GROS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Exclusive breastfeeding is currently recommended until at least 6 months of postnatal age, due to maternal breast milk (BM) unique composition and beneficial properties. In fact, BM modifies itself according to gestational age (GA) at birth, adapting its composition to neonatal requests during lactation. Multiple births represent about 3% of the whole pregnancies; such neonates result more vulnerable than full-term newborns, due to lower GA and birth weight (BW) and the higher incidence of perinatal complications. Although an adequate nutrition is fundamental for twins and other multiples, studies on this topic are lacking. We collected and analyzed BM from mothers of 19 twins and 5 triplets showing GA < 33 weeks and BW < 1500 g, comparing it to a control group of 28 preterm singletons. As a result, at GA ≤ 28 weeks, we observed that protein content is higher in BM for multiples (1.53 vs. 1.29 g per 100 ml), lactose concentration is greater in BM for singletons (6.72 vs. 6.34 g per 100 ml) and GA results the most relevant factor influencing BM protein composition. BM for multiples results higher in proteins and lower in lactose, if compared with singleton's samples; this could promote and sustain growth and organ development in this vulnerable category. BM from multiples shows a trophic and immunologic role, since these neonates often show lower GA and BW instead of singletons. These findings could help in optimizing nutritional strategies and improving BM individualized fortification.

Twins are often born small and early and have increased risk of obesity and diabetes later in life. Twin conception in sheep, regardless of whether the pregnancy continues as twins or is reduced to singleton in early gestation, alters offspring growth trajectory and body composition in young adulthood. We hypothesized that twin conception would result in insulin resistance in adulthood, with insulin-resistant adipose tissue and skeletal muscle phenotypes. At 3 years of age, body weight was not different among singletons, twins, and reductions; females weighed less than males. Singletons were leaner than reductions, with twins intermediate. Twins and reductions had decreased insulin sensitivity compared with singletons (singletons: mean [standard error of the mean]: 4.75 [0.4], twins: 3.34 [0.3], reductions: 3.67 [0.2] mg·I μU -1 ·kg -1 ·min -1 , P < .01). There were no group differences in adipocyte size, adipose tissue, or circulating tumor necrosis factor α, monocyte chemoattractant protein 1, or interleukin 6 concentrations. In males, omental and subcutaneous adipose SLC2A4 was 1.5- to 2.0-fold greater in twins and reductions than in singletons ( P < .01) and SLC2A1 was greater in reductions than in singletons. Skeletal muscle IRS-1 was decreased in male twins but increased in female twins, compared to singletons ( P ≤ .01), with no effect on reductions in either sex. Skeletal muscle SLC2A4 was decreased in female twins and reductions but elevated in male twins and reductions compared to singletons ( P ≤ .01). We conclude that adult twin insulin resistance is not due to adipose tissue phenotype, but potentially phenotypic effects in skeletal muscle, and obesity is a result of twin conception per se with its origins in early gestation.

Objective: We aimed to compare maternal characteristics and dysglycemia after delivery in women with gestational diabetes mellitus (GDM) according to pregnancy being multiple (MP) or singleton (SP). The hypothesis was that women with GDM and MP would have a milder glycemic abnormality before and after pregnancy than those with SP., Methods: We performed a cohort study of 2908 women giving birth between 1986 and 2009. Logistic regression was performed to discriminate between MP and SP after anamnestic pre-pregnancy characteristics. Kaplan-Meier and Cox regression analyses were performed to assess if MP was independently associated with both impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and diabetes after delivery., Results: Family history of diabetes was the only independent anamnestic pre-pregnancy characteristic discriminating MP versus SP, OR 2.04 (95% CI 1.12, 3.70, p 0.019). The median time to progress to IFG/IGT was 7.52 years in SP (95% CI 6.92, 8.13) and 7.41 in MP (95% CI 3.84, 10.98), ns and the progression to DM did not differ. In addition, MP was not associated to IFG/IGT or to DM in the Cox regression analysis., Conclusions: In this cohort of women with GDM, those with MP did not demonstrate a lesser degree of dysglycemia after controlling for other pregnancy characteristics and pregnancy-independent factors.

In 2012 there were 135,943 infants of multiple pregnancies born in the United States, nearly a 2-fold increase since 1980, with twins accounting for 96% of all multiple births. To date, most perinatal morbidities associated with multiple births have proven resistant to technological or pharmaceutical interventions. Maternal nutrition can have a profound effect on the course and outcome of multiple pregnancy, with the goal of achieving optimal intrauterine growth and birthweights, and minimizing prenatal and perinatal complications for the mother and her children.

Exposure to poor maternal nutrition around the time of conception results in an early prepartum activation of the fetal pituitary-adrenal axis and in increased adrenal growth and stress response after birth associated with epigenetic changes in a differentially methylated region (DMR) of adrenal IGF2/H19. We have determined the effects of maternal undernutrition during the periconceptional period (PCUN: 70% of control intake from 60 days before until 6 days after conception) and early preimplantation period (PIUN: 70% of control intake for 6 days after conception) on fetal plasma ACTH and cortisol concentrations and fetal adrenal ACTHR, StAR, 3βHSD, CYP11B, CYP17, TGFβ1, IGF1, IGF1R, IGF2, and IGF2R mRNA expression and the methylation level of sites within the DMRs of IGF2/H19 and IGF2R in the adrenal of twin and singleton fetuses at 136-138 days gestation. Being a twin resulted in a delayed prepartum increase in fetal ACTH and in a lower cortisol response to CRH in the control but not PCUN and PIUN groups. PCUN, but not PIUN, resulted in an increase in adrenal weight and CYP17 expression in singletons, a decrease in adrenal IGF2 expression in singletons, and an increase in adrenal IGF2R expression in both twins and singletons. IGF2/H19 and IGF2R DMR methylation levels and ACTHR expression were lower in the twin adrenal. Thus, exposure of the oocyte and embryo to maternal undernutrition or to the environment of a twin pregnancy have differential effects on epigenetic and other factors that regulate fetal adrenal growth and IGF2 and IGF2R expression., (Copyright © 2014 the American Physiological Society.)

For the past three decades, assisted reproductive technologies (ART) have revolutionized infertility treatments. The use of ART is thought to be safe. However, early investigations suggested that children born as a result of ART had higher risk of diseases with epigenetic etiologies, including imprinting disorders caused by a lack of maternal methylation at imprinting control elements. In addition, large epidemiology studies have highlighted an increased risk of obstetric complications, including severe intrauterine growth restriction (IUGR) in babies conceived using ART. It is plausible that the increased frequency of IUGR may be due to abnormal imprinting because these transcripts are key for normal fetal growth and development. To address this, we have collected a large cohort of placenta and cord blood samples from ART conceptions and compared the imprinting status with appropriate non-ART population. Using a custom DNA methylation array that simultaneously quantifies 25 imprinted differentially methylated regions, we observed similar epigenetic profiles between groups. A multiplex Sequenom iPLEX allelic expression assay revealed monoallelic expression for 11 imprinted transcripts in our placenta cohort. We also observe appropriate gestational age-dependent methylation dynamics at retrotransposable elements and promoters associated with growth genes in ART placental biopsies. This study confirms that children conceived by ART do not show variability in imprinted regulation and that loss-of-imprinting is not commonly associated with nonsyndromic IUGR or prematurity.

Hedgehog signaling is involved in regulation of ovarian function in Drosophila, but its role in regulating mammalian ovarian folliculogenesis is less clear. Therefore, gene expression of Indian hedgehog (IHH) and its type 1 receptor, patched 1 (PTCH1), were quantified in bovine granulosa (GC) or theca (TC) cells of small (1-5 mm) antral follicles by in situ hybridization and of larger (5-17 mm) antral follicles by real-time RT-PCR from ovaries of cyclic cows genetically selected (Twinner) or not selected (control) for twin ovulations. Expression of IHH mRNA was localized to GC and cumulus cells, whereas PTCH1 mRNA was greater in TC than in GC. Estrogen-active (E-A; follicular fluid concentration of estradiol > progesterone) versus estrogen-inactive follicles had a greater abundance of mRNA for IHH in GC and PTCH1 in TC. Abundance of IHH mRNA in GC was not affected by cow genotype, whereas TC PTCH1 mRNA was less in large E-A follicles of Twinners than in controls. In vitro, estradiol and wingless-type (WNT) 3A increased IHH mRNA in IGF1-treated GC. IGF1 and BMP4 treatments decreased PTCH1 mRNA in small TC. Estradiol and LH increased PTCH1 mRNA in IGF1-treated TC from large and small follicles, respectively. In summary, functional status of ovarian follicles was associated with differences in hedgehog signaling in GC and TC. We hypothesize that as follicles grow and develop, increased free IGF1 may suppress expression of IHH mRNA by GC and PTCH1 mRNA by TC, and these effects are regulated in a paracrine way by estradiol and other intra- and extragonadal factors.

Elevated concentrations of circulating progesterone (P₄) in the immediate post-ovulation period are associated with advancement of conceptus elongation in cattle. Superovulated (SOV) cattle have not only elevated plasma P₄ concentrations but also multiple embryos in the uterus because of the formation of multiple corpora lutea. We examined the relationship between plasma P₄ concentration and uterine glucose level in the immediate post-ovulation period and the presence and growth of multiple conceptuses in SOV cattle. SOV cattle were artificially inseminated with frozen-thawed semen at standing estrus (day 0), and the conceptuses were recovered by nonsurgical flushing of the uterus on day 13. In the SOV cattle, there were quadratic relationships between plasma P₄ concentration on days 4, 5 and 7 and conceptus length and between number of conceptuses in the uterus and conceptus length. These results suggest that conceptus growth in SOV cattle is regulated by both systemic P₄ level and number of conceptuses and that there are ranges of plasma P₄ concentrations and numbers of conceptuses in the uterus that are suitable for conceptus growth and development. Plasma P₄ concentrations on days 5 and 7, but not the numbers of conceptuses, were quadratically correlated with uterine glucose levels on day 13 in SOV cattle. In addition, conceptus length was positively correlated with uterine glucose level in SOV cattle. Accordingly, regardless of the number of conceptuses in the uterus, the plasma P₄ concentration was well correlated with the regulation of conceptus growth via changes in uterine glucose levels in SOV cattle.

Objective: We aimed to investigate the effects of progesterone on gene expression and function of both myometrium and circulating leukocytes., Methods: We recruited women participating in a randomized clinical trial of progesterone to prevent preterm delivery. These participants had a twin pregnancy and were managed in 1 of 2 tertiary referral centers. Participants were treated with progesterone (90 mg vaginally) or placebo from 24 to 34 weeks of pregnancy. The outcome measures were myometrial and leukocyte gene expression and expression of cell surface markers in circulating leukocytes, all quantified ex vivo., Results: Prolonged in vivo administration of progesterone inhibited myometrial expression of connexins 26 and 43, endothelial nitric acid synthase (eNOS), and the prostaglandin receptor EP2 ex vivo. Administration of progesterone also increased numbers of circulating neutrophils while decreasing lymphocyte proportions and decreasing neutrophil CD11b expression., Conclusion: The observed effects of prolonged in vivo administration of progesterone will minimize the ability of the uterus to contract as a synctium and the ability of peripheral blood leukocytes to migrate into the myometrium during parturition. We suggest that these are putative mechanisms by which progesterone might prevent preterm birth in women at high risk.

The present study evaluated the interaction of pregnancy type [PT; single (S) vs. twin (T)] and dry period feeding management [D; close-up (CU) diet (NE(l) = 1.54 Mcal/kg of DM)] throughout the entire dry period (8W) vs. far-off (FO) diet (NE(l) = 1.32 Mcal/kg of DM) from 60 to 21 d before expected calving date (ECD) followed by CU diet until calving (3W). Treatments were arranged in a 2 x 2 factorial with a randomized block design with primiparous (n = 8) and multiparous (n = 39) Holstein cows. We hypothesized that increasing the duration of feeding a CU diet would improve metabolic status and lactation performance for cows with T, but not for cows with S. All cows were fed similarly in late lactation (90 to 60 d before ECD; diet NE(l) = 1.58 Mcal/kg of DM) and in early lactation (calving to 105 DIM; diet NE(l) = 1.71 Mcal/kg of DM). Prepartum DMI as percentage of BW did not differ (P > 0.10) with D but tended to be greater (P = 0.10) for cows with S than with T. Cows with T tended to have greater (P = 0.08) BW than cows with S, but conceptus-free BW was less (P = 0.001) for cows with T than for cows with S. No differences (P > 0.10) were detected in prepartum BCS or BCS change with PT or D. Energy balance (EB) was greater for cows with S than with T (P < 0.001) and for cows fed 8W vs. 3W (P = 0.01). Cows with T had greater (P < 0.001) NEFA and a tendency for greater liver triglycerides (TG; P = 0.07) and plasma beta-hydroxybutyrate (BHBA; P = 0.06) than cows with S. Prepartum cows fed 3W had greater (P = 0.01) liver TG and greater (P = 0.02) plasma NEFA, but less (P = 0.02) plasma BHBA than cows fed 8W. Plasma glucose (P < 0.004) and liver glycogen (P = 0.02) were less for cows with T but were not affected (P > 0.10) by D. Postpartum, there was no effect (P > 0.1) of PT or D on mean DMI as percentage of BW, BW, and BCS, but there was an interaction (P = 0.02) of PT x D for mean BCS. Cows that calved T were in a more positive (P = 0.004) EB than cows that calved S. Milk production was 5.2 kg/d greater (P = 0.04) for cows fed 8W; however, they were in less (P = 0.01) EB than cows that received 3W. Postpartum cows that calved T had decreased concentrations of plasma NEFA (P = 0.02) and liver TG (P = 0.04) but greater concentrations of plasma glucose (P = 0.03) than cows that calved S. Plasma BHBA (P = 0.07) and NEFA tended (P = 0.06) to be greater for cows that received 8W than 3W. Neither PT nor D affected (P > 0.1) plasma glucose and liver glycogen. There was a tendency for an interaction of PT x D for plasma NEFA and liver TG. In contrast to our hypothesis, response to D was independent of PT. Based on milk production data from the present experiment, 8W is a more desirable feeding strategy than 3W.

Follicles > or = 5 mm were ablated at 4 day post-ovulation in heifers to induce a follicular wave, and prostaglandin F(2alpha) was given at day 6 to increase the incidence of double ovulations. Follicle diameters and plasma hormone concentrations were compared between single ovulators (n=12) and double ovulators (n=8). In double ovulators, the interval from follicle deviation to the peak of the pre-ovulatory LH surge was shorter (1.9+/-0.2 vs 2.5+/-0.2 days; P<0.02) and diameter of the largest pre-ovulatory follicle was smaller (12.2+/-0.5 vs 13.3+/-0.3 mm; P<0.02). The LH concentrations of the pre-ovulatory surge did not differ between single and double ovulators for 24 h on each side of the peak. When data were normalised to LH peak, the peak of the pre-ovulatory FSH and oestradiol (E(2)) surges occurred in synchrony with the peak of LH surge for both groups. Concentration of FSH for 24 h on each side of the peak showed a group effect (P<0.0001) from lower concentration in the double ovulators. A group-by-hour interaction (P<0.008) for E(2) reflected greater concentration in the double ovulators before and at the peak. Results indicated that two pre-ovulatory follicles resulted in an earlier and greater E(2) increase, leading to lower FSH concentration, an earlier LH surge, and ovulation at a smaller diameter. In conclusion, the difference in hormone concentrations during the pre-ovulatory period was an effect rather than a cause of double ovulations.

The aim of this study was the clearance assessment of renal function in single- and twin-pregnant goats and a comparison of selected parameters associated with calcium-phosphate management in terms of litter size. Clearance studies were carried out on 16 pregnant Polish White Improved goats (8 single pregnancies and 8 twin pregnancies). It was demonstrated that the kidneys of pregnant goats regulate the calcium-phosphate balance to a great extent. In spite of observed differences in parameters of renal functions, plasma calcium and inorganic phosphorus concentrations were comparable with normal reference values in further weeks of pregnancy. Significant differences in renal function between single and twin pregnancies were not observed. Gut absorption and/or bone tissue metabolism seem important for the maintenance of appropriate calcium-phosphate status.

Maturation of the fetal hypothalamus-pituitary-adrenal axis is critical for the timely somatic development of the fetus and readiness for birth. Recently, we proposed that prostaglandin generation within the fetal central nervous system is critical for the modulation of hypotension-induced fetal ACTH secretion. The present study was designed to test the hypothesis that the preparturient increase in fetal ACTH secretion is dependent upon fetal central nervous system prostaglandin synthesis mediated by the activity of prostaglandin endoperoxide synthase (PGHS)-2 (cyclooxygenase-2) in the fetal brain. We performed two studies in chronically catheterized fetal sheep. In the first study, we infused nimesulide or vehicle intracerebroventricularly (i.c.v) into singleton fetal sheep and collected blood samples until spontaneous parturition. Nimesulide significantly delayed parturition, and inhibited fetal ACTH and proopiomelanocortin secretion but did not prevent the preparturient increase in fetal plasma cortisol concentration. In the second study, we used twin fetuses. One fetus received intracerebroventricular nimesulide and the other intracerebroventricular vehicle. Nimesulide reduced brain tissue concentrations of prostaglandin estradiol, while not affecting plasma prostaglandin E(2) concentrations, demonstrating an action restricted to the fetal brain. Nimesulide reduced PGHS-2 mRNA and increased PGHS-2 protein, while not altering PGHS-1 mRNA or protein in most brain regions, suggesting an effect of the inhibitor on PGHS-2 turnover and relative specificity for PGHS-2 in vivo. We conclude that the preparturient increase in fetal ACTH and proopiomelanocortin is dependent upon the activity of PGHS-2 in the fetal brain. However, we also conclude that the timing of parturition is not solely dependent upon ACTH in this species.

In normal pregnancy, the fetal membranes become increasingly distended towards term and in multifetal gestations they become over-distended. Apoptosis of the amniotic epithelium increases with advancing gestation and may contribute to fetal membrane weakening and rupture. The effects of chronic static stretching for 36h have been investigated using primary amniotic epithelial cells. Pre-B cell colony-enhancing factor (PBEF) is a stretch-responsive cytokine and expression of its gene, intracellular and secreted protein were all significantly increased by 4h and its secretion sustained over 36h, contrasting with the rapid increase and decline in expression of IL-8. Increased expression of SIRT1 and decreased p53 paralleled the changes in PBEF, are known to be responsive to PBEF, and contribute to cell survival. Distension had no effects on proliferation or necrosis but protected the cells from apoptosis, knocking-down PBEF with antisense probes abrogated this protective effect. There was increased immunostaining of PBEF in the compact layer of the amnion in multifetal tissues and significantly fewer apoptotic amniotic epithelial cells. These results show that chronic stretching of the amniotic epithelial cells increases PBEF expression, which protects them from apoptosis.

For singleton, twin, and triplet pregnancies, uteri were collected on day 140 of pregnancy. For each ewe (n = 18), placentomes were fixed by arterial perfusion supplying the fetal (cotyledon) and maternal placenta (caruncle). Tissue sections were stained for determination of vascularity by image analysis. Further, protein expression for factor VIII, vascular endothelial growth factor (VEGF) and its receptor, VEGFR1, as well as basic fibroblast growth factor (FGF2) and its receptor, FGFR, in tissue sections was determined by immunohistochemistry and image analyses. Cotyledonary and caruncular samples were analyzed for expression of mRNA for Vegf and its two receptors, Vegfr1 and Vegfr2, as well as Fgf2 and Fgfr. Fetal number did not affect placental capillary density or factor VIII expression, whereas increased fetal number reduced total cotyledon and caruncle capillary volume. While expression of Vegf, Vegfr1, Vegfr2, and Fgfr mRNA in cotyledonary but not caruncular tissue was greater in twin pregnancies compared to singleton and triplet pregnancies, protein expression of VEGF in the placentome decreased with increasing numbers of fetuses, VEGFR1 did not change, and FGFR was greater in twin versus singleton and triplet pregnancies. Fetal number did not affect the expression of Fgf2 mRNA in placental tissues, whereas FGF2 protein expression was less in triplet compared to singleton and twin pregnancies. Reduced fetal and placental weights in twins and/or triplet pregnancies are associated with an overall decrease in total placental vascularity, VEGF and FGF2 and/or FGFR protein expression, but not in angiogenic factor mRNA expression or VEGFR1 protein expression in sheep.

Objective: Intrauterine growth restriction (IUGR) is characterized by decreased placental perfusion. Low oxygen has been shown to increase soluble fms-like tyrosine kinase 1 (sFlt-1) expression in the human placenta. The objective of this study was to examine sFlt-1 expression in different types of IUGR pregnancies, including early-onset severe cases characterized by abnormal umbilical and uterine artery Doppler and discordant IUGR twins in which the normal cotwin represents the optimal control because both placentas share the same uterine environment., Patients: Placentas from four subgroups were collected: early severe IUGR with umbilical artery absent end diastolic flow (n = 19), small for gestational age with normal uterine and umbilical artery Doppler (n = 11), severely growth-restricted dichorionic and monochorionic twins with abnormal umbilical artery Doppler (n = 9), preeclamptic twins (n = 3), and age-matched normal singletons (n = 19) and twin controls (n = 8)., Results: Expression of sFlt-1 mRNA and protein was significantly increased in IUGR placentas compared with small for gestational age and normal control placentas. sFlt-1 expression levels were also significantly greater in the small IUGR twin placentas from discordant twin pregnancies compared with the normal cotwin. In preeclamptic twins, sFlt-1 expression was increased in only one of the two placentas., Conclusions: Our results demonstrate that sFlt-1 expression is increased in severe IUGR placentas with abnormal umbilical artery Doppler of singletons and also in discordant IUGR twins. Reduced placental perfusion may contribute to the increased expression of sFlt-1 in IUGR pregnancies. Our data are compatible with differential sFlt-1 expression in placentas from discordant twins.

Preterm birth remains a major cause of perinatal mortality and long term handicap in surviving infants. This is one of the most important clinical problems in Europe and across the world. While some preterm births are iatrogenic, associated with severe complications of pregnancy (e.g. hypertensive disorders, antepartum haemorrhage, infection), or the result of multiple pregnancies following assisted reproduction, a high proportion of preterm births occur following spontaneous preterm labour of unknown cause. Early intervention in this group of women would have a significant impact on neonatal mortality and morbidity figures. However, the endocrine changes preceding parturition in women remain elusive and this makes it difficult to predict spontaneous labour at term, let alone preterm labour. Moreover our understanding of myometrial physiology remains rudimentary, limiting our options to devise improved pharmacological strategies to control uterine contractility when this is indicated. There is a need for concerted European and international research efforts to improve our knowledge of the mechanism of labour in women, to identify diagnostic markers to predict preterm labour and to develop uterine selective drugs to inhibit uterine contractions in a safe and efficient manner. This aim will be achieved by multidisciplinary research efforts from academics and industry, using traditional laboratory and clinical research methods, as well as novel technologies.

Objective: To assess if amniotic fluid alpha-fetoprotein (AFAFP) could be useful to determine if both sacs are sampled during an amniocentesis for twin pregnancies., Method: We reviewed all amniocenteses performed on twin pregnancies over a 5-year period. Inclusion criteria were restricted to pregnancies where both karyotypes and AFAFP were available on each fetus. Pregnancies complicated by fetal anomalies were excluded. The following information was obtained: maternal age, gestational age at the procedure, karyotypes, AFAFP values, pregnancy and neonatal outcome. Placental pathology reports were used to confirm chorionicity. Analysis was performed to evaluate the impact of the fetal gender and chorionicity on the AFAFP values., Results: 260 pregnancies were reviewed. Mean maternal age was 36.9 years (33.6, 40.1). Gestational age at the time of the procedure was 16.2 weeks (14.5, 17.9). Complications included 1.8% of misdiagnosis (discrepancy between karyotype and gender). The difference of AFAFP values between the two fetuses was statistically larger in dichorionic pregnancies than in monochorionic gestations. Fetal gender had no influence on the AFAFP., Conclusion: Amniocentesis in twin pregnancies is associated with a 1.8% risk of misdiagnosis. AFAFP can help to assess the chorionicity of a twin pregnancy. When the difference between the two values is <0.2 MoM and the chorionicity was thought to be dichorionic and the two karyotypes are similar, then failure to sample both sacs should be suspected., ((c) 2007 S. Karger AG, Basel.)

Multiple pregnancy represents a state of magnified nutritional requirements, resulting in a greater nutrient drain on maternal resources and an accelerated depletion of nutritional reserves. The accelerated starvation which occurs in pregnancy is exaggerated with a multiple gestation, particularly during the second half of pregnancy, with more rapid depletion of glycogen stores and resultant metabolism of fat between meals and during an overnight fast. A reduced glucose stream from mother to fetus results in slower fetal growth, smaller birth size, as well as a higher risk of preterm labor and preterm birth. For this reason, diet therapy with a diabetic regimen of 20% of calories from protein, 40% of calories from carbohydrate, and 40% of calories from fat may be particularly useful. Iron-deficiency anemia has also been linked to preterm delivery and other adverse pregnancy outcomes. Mobilization of maternal iron stores, in addition to an adequate amount and pattern of gestational weight gain (including BMI-specific weight gain goals by 20 and 28 weeks gestation), has been associated with significantly better fetal growth and longer gestations in twin pregnancies. Supplementation with calcium, magnesium, and zinc, as well as multivitamins and essential fatty acids may also reduce pregnancy complications and improve postnatal health for infants born from a multiple gestation. Diet therapy for women pregnant with multiples is an important component of effective prenatal care.

Phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) is secreted by decidual cells and may leak into cervical secretions during detachment of the fetal membrane. The aim of this study was to determine whether a rapid bedside test for phIGFBP-1 predicts preterm birth in women with preterm uterine contractions. This was a prospective study of pregnant women who sought medical care for symptoms of preterm labor. Cervical swabs were assayed for the presence of phIGFBP-1 by a rapid bedside test. Sixty-four patients were enrolled. Eleven of them (17%) delivered preterm (< 35 weeks). phIGFBP-1 in cervical secretions predicted preterm birth with a sensitivity of 72.7%, a specificity of 83.0%, a positive predictive value of 47.0%, and negative predictive value of 93.6%. Positive phIGFBP-1 bedside test in women with preterm uterine contractions may indicate a significant risk for subsequent preterm birth. The absence of phIGBP-1 is a reassuring sign that the likelihood of preterm birth is low.

Objective: The aims of the study were to compare the pharmacokinetics of betamethasone in singleton pregnancy with the pharmacokinetics in twin pregnancy and to assess the adrenal suppression produced by betamethasone., Study Design: We measured serial betamethasone and cortisol levels in 30 singleton and 21 twin pregnancies after the first dose of betamethasone and calculated the pharmacokinetic parameters for betamethasone including volume of distribution, half-life, and clearance. We also measured cord and maternal blood levels of betamethasone at the birth of infants of 13 singleton and 9 twin pregnancies., Results: The half-life of betamethasone in mothers with twin pregnancies was significantly shorter than that in mothers with singleton pregnancies (7.2 +/-2.4 versus 9.0 +/- 2.7 hours; P <.017). Clearance of betamethasone in the twin pregnancies appeared greater than in singleton pregnancies (8.4 +/- 6.4 versus 5.7+/- 3.1 L/h; P =.06) but did not reach statistical significance. Volume of distribution was similar in the two groups. Because the time between the last dose of betamethasone and birth varied widely (range, 2-158 hours), mothers with a longer interval after treatment tended to have a higher cord-to-maternal betamethasone ratio than did mothers with a shorter interval in both twin and singleton pregnancies. This finding indicated delayed fetal clearance, but the correlation was weak (R (2) = 0.29 for twins and 0.08 for singletons)., Conclusion: The shorter half-life of betamethasone in twin pregnancy than in singleton pregnancy may cause the level of betamethasone to be subtherapeutic for lung maturation in twin pregnancy.

Objective: We tested the hypothesis that preterm delivery in women with twins or polyhydramnios is associated with enhanced expression and activity of cyclooxygenase type 2 in the amnion., Study Design: We obtained amniotic tissue samples from women undergoing preterm delivery complicated by either twins or polyhydramnios and also from women undergoing preterm cesarean delivery before or after labor. We measured amniotic prostaglandin E2 content and determined cyclooxygenase type 1 and type 2 expressions. We inhibited cyclooxygenase type 1 and type 2 activities with selective inhibitors., Results: Preterm delivery attributed to twins or polyhydramnios was associated with higher prostaglandin E2 production and enhanced amniotic expression of cyclooxygenase type 2. In contrast, cyclooxygenase type 1 expression was unchanged. Incubation of amniotic samples in vitro with either indomethacin or the selective cyclooxygenase type 2 inhibitor SC-236, but not with the cyclooxygenase type 1 inhibitor SC-560, effectively reduced prostaglandin E2 production., Conclusion: Preterm delivery related to multiple gestation or polyhydramnios was associated with enhanced amniotic expression and activity of cyclooxygenase type 2.

We localised three important enzymes histochemically in placental trophoblasts from women who gave birth to dichorionic discordant twins, in which the co-twin was affected by foetal growth restriction (FGR). The enzymes studied were adenosine diphosphate-degrading enzyme (ADP-degrading enzyme, plasma membrane enzyme), cytochrome c oxidase (mitochondrial enzyme), and glucose-6-phosphatase (endoplasmic reticular enzyme). We compared these enzyme activities and their distribution patterns among placentas of the smaller (FGR) co-twin, larger co-twin, pre-eclamptic singleton with FGR, and normal singletons with birth weight of appropriate for their gestational ages. In FGR co-twin placentas, the intensity and localisation pattern of these three enzymes did not differ from those seen in the larger co-twin and normal singleton placentas. Decreased ADP-degrading activity and cytochrome c oxidase negative mitochondria, which were characteristic features of pre-eclamptic trophoblasts, were not observed in FGR co-twin placentas. These observations indicated that, in the FGR co-twin, enzyme-histochemically detectable trophoblastic cell dysfunction may be absent, or if present, less prominent, compared with pre-eclamptic FGR. We previously reported that placental trophoblasts from singleton idiopathic FGR also showed no reduction in these enzyme activities. In mechanism and pathophysiology, FGR in dichorionic discordant twins may be quite different from pre-eclamptic FGR, but somewhat resembles idiopathic FGR, though all three disorders lead to placental insufficiency, resulting in limited foetal growth.

The aim of the study was to investigate role of the feto-placental unit in the pregnancy-induced increase in maternal bone metabolism. To achieve this, circulating concentrations of carboxy terminal pro-peptide of type I pro-collagen (PICP, a marker of bone formation) and cross-linked carboxy terminal telopeptide of type I collagen (ICTP, a marker of bone resorption) were measured in three groups of pregnant women. Group 1 comprised 12 women with singleton pregnancies; group 2, nine women with twin pregnancies; and group 3, 19 women with multifetal pregnancies (> or =3 fetuses) before and after selective fetal reduction to twin pregnancies. Blood samples were obtained at 10-12 weeks gestation (groups 1-3, pre-fetal reduction in group 3) and 4 weeks and 8 weeks later (groups 2 and 3). Before fetal reduction there was a significant correlation between the number of fetuses and the concentrations of both PICP and ICTP (r = 0.503 and P = 0.001 and r = 0.573 and P < 0.001 respectively). The circulating concentrations of PICP and ICTP were significantly higher in the pre-reduction multifetal pregnancies than in the twin pregnancies (P < 0.001 and P = 0.0013 respectively). The circulating concentrations of ICTP in multifetal pregnancies fell by 4 weeks after fetal reduction to those observed in control twins. Concentrations of PICP were unaltered after fetal reduction. Higher order multiple pregnancies had the greatest decline in ICTP concentrations. These data suggest that the increased bone turnover observed in the multifetal pregnancies is due to a factor derived from the feto-placental unit and that this factor acts primarily to stimulate bone resorption.

Objective: We sought to determine the accuracy of amniotic fluid volume estimation (visually) in diamniotic twin pregnancy versus ultrasonography techniques., Study Design: In this prospective study the volume of each sac in 23 sets of diamniotic twin pregnancies was subjectively and objectively estimated by a second-year obstetric resident, nurse sonographer, maternal-fetal medicine fellow, and maternal-fetal medicine staff. The actual volume was confirmed by amniocentesis and a dye-dilution technique., Results: There was no difference in the total number of correct estimates of volume by level of operator experience (P =.98), ultrasonography technique (P =.87), or combined subjective versus objective correct estimates (P =.87). Identification of low volume was not different among the four evaluators (P =.48), but the percentage of correct estimates was poor (7%-29%). The 2-diameter pocket was a better predictor of oligohydramnios (57%) than the amniotic fluid index or the largest vertical pocket (12.5%; P =.002)., Conclusion: The extremes of volume (low or high) are poorly identified by the subjective or objective assessment of volume.

Hyperreactio luteinalis is characterized by moderate to marked cystic enlargement of the ovaries related to multiple theca lutein cysts and is associated with very high sex steroid concentrations. It is a rare condition especially in the first trimester. The case described below is believed to be the only case of hyperreactio luteinalis reported following frozen embryo transfer. This case provides an opportunity to gain further insight into the mechanism responsible for this unusual condition. The 30 year old woman demonstrated a slightly elevated LH/FSH ratio (5 and 3 mIU/ml respectively) and normal baseline androgen concentrations. Two years following oocyte retrieval she had a second frozen embryo transfer. The ovaries were normal size when the embryos were transferred and androgens were still normal. The ovaries did not begin to enlarge until 51 days from transfer. A dichorionic intrauterine pregnancy with monozygotic twins in the left gestational sac was seen. Eventually, 86 days from transfer, the ovaries enlarged to 145x103x116 mm right; and 83x95x117 mm left. Serum oestradiol was 30 078 pg/ml, beta-human chorionic gonadotrophin (HCG) 239 920 mIU/ml, serum progesterone >160 ng/ml, total testosterone 2254 ng/dl, free testosterone 42.3 pg/ml and androstenedione 7328 ng/dl. Throughout the first trimester, serum FSH was <1 mIU/ml. Thus, neither FSH nor a corpus luteum is necessary to initiate this syndrome.

Objective: We sought to investigate the amniotic fluid index for individual gestational sacs of twin pregnancies., Study Design: Four hundred eighty-eight patients with normal diamniotic twins were examined between 14 and 40 weeks' gestation. The dividing membrane between twin fetuses was identified. An amniotic fluid index was then obtained for each gestational sac., Results: The median amniotic fluid index in individual twin gestational sacs rises slowly from 14 to 16 weeks' gestation to 23 to 28 weeks' gestation and then gradually declines. The median amniotic fluid index values by gestational age for twin A and twin B are not statistically different. Although twin pregnancies have a slightly lower median amniotic fluid index value than singleton pregnancies, the difference is also not statistically significant., Conclusion: Individual amniotic fluid indices can be obtained in twin pregnancies, and the values are comparable with those of singleton gestations.

Our objective for this study was to determine the pattern of nutrient flux across the portal-drained viscera (PDV) and liver in ewes with varying numbers of fetuses. Catheters were placed in the hepatic portal vein, a branch of the hepatic vein, a mesenteric vein, and the abdominal aorta of ewes. Blood flow and net nutrient release across the PDV and liver were determined before exposure to rams. Ewes were then mated, which resulted in two ewes not pregnant and in six ewes with single and 11 ewes with twin lambs. Additional measurements were taken 103, 82, 61, 39, 19, and 6 d before parturition. Net PDV glucose release did not differ from zero (-.4 +/- 8.4 mmol/h; P = .58). In ewes with singles, premating net hepatic glucose release was 34.4 +/- 2.4 mmol/h, and 19 d before parturition it was 46.2 +/- 3.8 mmol/h. In ewes with twins, premating net hepatic glucose release was 36.8 +/- 2.7 mmol/h, and 19 d before parturition it was 47.4 +/- 2.8 mmol/h. Net PDV lactate release did not differ with litter size (P = .58) or days from parturition (P = .14; 9.7 +/- 4.6 mmol/h). Net lactate uptake by the liver increased in pregnant ewes as the pregnancy progressed (P < .001). The hepatic extraction ratio for lactate increased in late pregnancy (P = .02). Net PDV and hepatic release of acetate and propionate were not different with litter size or days from parturition. Hepatic extraction ratios of VFA did not differ with litter size or day from parturition. The patterns of change in hepatic metabolite fluxes are similar to the patterns of change in gravid uterus metabolite uptake. Hepatic lactate uptake seems to be regulated during pregnancy.

We prospectively evaluated the antenatal changes in antithrombin-III (AT-III) activity and liver enzymes in a woman with a triplet pregnancy. A gradual decline in AT-III activity occurred in the absence of clinical signs of preeclampsia and preceded the onset of the typical HELLP syndrome in this patient. Monitoring of AT-III activity might help to avoid the development of severe HELLP syndrome.

Objective: To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies., Participants: One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden., Methods: Cervical or vaginal fluid was sampled and determined for fetal fibronectin (> or = 0.05 microgram/mL was used as cutoff), endotoxin (> or = 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals., Main Outcome Measures: Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity., Results: All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2.2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff < or = 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity., Conclusions: Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

To assess changes in the serum uric acid level in the third trimester of twin pregnancies, a total of 152 consecutive women with twin pregnancies were examined. Serum uric acid levels were analyzed in the women at varying gestational weeks in the presence or absence of preeclampsia. A receiver operating characteristic curve was used to determine the optimal cutoff value of serum uric acid between 30 and 31 weeks of gestation predicting subsequent development of preeclampsia. Forty-four women (29%) developed preeclampsia (preeclampsia group) at 33.2 +/- 1.9 weeks (mean +/- SD) and gave birth at 35.4 +/- 1.5 weeks of gestation. The remaining 108 women (71%) gave birth at 35.6 +/- 1.7 weeks of gestation (control group without preeclampsia). Serum uric acid levels rose gradually with advancing gestation in both groups. In the preeclampsia group, they were already increased at 30-31 weeks of gestation and corresponded to those seen in the control group at 37 weeks. The cutoff value at 30-31 weeks was 5.5 mg/dl, with a sensitivity of 73% and a specificity of 74%. These results suggest that an elevation in serum urate preceded the onset of preeclampsia. Determination of the serum level of uric acid between 30 and 31 weeks of gestation was useful for detecting a higher risk of late-onset preeclampsia in twin pregnancies.

Purpose: This study measured serum early pregnancy factor (EPF) in pregnant red deer (Cervus elaphus) and ascertained whether EPF synthesis is associated with implantation., Methods: Serial serum samples were taken from mated hinds up to 42 days postconception and analyzed for EPF activity using the rosette inhibition test. EPF activity was then correlated with calving records and stages of preimplantation development., Results: EPF was detected in all pregnant animals, with a twin pregnancy giving increased EPF activity. Three animals gave an EPF response following fertilization but failed to continue beyond the preimplantation embryo stage. The increase in EPF synthesis previously associated with implantation in other mammals occurred at the blastocyst stage in red deer., Conclusions: EPF synthesis in red deer (Cervus elaphus) is consistent with the preimplantation period, as occurs in other mammals. However, the second phase of the biphasic increase in early pregnancy factor production is associated with blastocyst formation, not implantation.

The essential fatty acid (EFA) status of full-term infants born after an uneventful, singleton pregnancy has been reported to be marginal. If this low EFA status is caused by a limiting maternal EFA supply, the higher total fetal EFA demand associated with a multiple pregnancy would result in an even lower EFA status of the infants born after a multiple pregnancy. Therefore, we compared the EFA status at birth of 30 pairs of twins, seven sets of triplets, and one set of quintuplets with that of 94 infants (51 preterm, 43 full-term) born after a singleton pregnancy. Phospholipid-associated EFA profiles of the umbilical vessel walls, considered a longer-term reflection of the fetal EFA status, were studied. After correction for gestational age at birth, levels of n-6 and n-3 EFAs were generally lower, while levels of EFA-deficiency indicating n-9 polyunsaturated fatty acids were significantly higher both in the draining umbilical arteries and the supplying veins of infants born after a multiple pregnancy. EFA profiles of twins and triplets were similar, but the average EFA status of the set of quintuplets was lower than that of twins and triplets. In conclusion, the observation that the EFA status of infants born after a multiple pregnancy is lower than that of infants born after a singleton pregnancy supports the view that the maternal EFA supply to the fetus is limiting. Considering the importance of EFAs and their longer chain derivatives for proper growth and development, this finding warrants further studies of the adequacy of the maternal EFA intake during pregnancy.

Objective: To test the hypothesis that maternal bone turnover and mineral stress are greater in multiple pregnancy than in singleton pregnancy., Methods: We measured serum markers of bone turnover and mineral stress in 17 multiple and 30 singleton pregnancies during the third trimester., Results: Serum 25(OH) vitamin D, a marker of vitamin D intake, was higher (61 +/- 5 versus 39 +/- 2 ng/mL, P < .001), and 1,25(OH)2 vitamin D was lower (50 [95% confidence interval (CI) 24-102] versus 64 pg/mL [95% CI 30-135], P = .03) in multiple than in singleton pregnancy. Carboxyterminal telopeptide of type I collagen, a marker of bone resorption, increased with gestational duration and was higher in multiple gestation (5.8 [95% CI 3.3-10.1] versus 4.4 ng/mL [95% CI 2.5-7.8], P = .005). Carboxyl-terminal propeptide of type 1 procollagen, a marker of bone formation, increased with gestational duration and was not different between groups (110 [95% CI 36-337] versus 99 ng/mL [95% CI 34-286], P = .5). Calcitonin increased with gestational duration and was not different between groups (7.0 [95% CI 3.7-13.0] versus 7.8 pg/mL [95% CI 4.0-15.4], P = .37). Parathyroid hormone was not different between groups and decreased with increasing maternal age., Conclusion: Bone turnover indices increased with gestational duration. The bone resorption index was greater in multiple than in singleton gestation. Serum 25(OH) vitamin D was greater and 1,25(OH)2 vitamin D was lower in multiple gestation, presumably because of greater consumption of vitamin D and minerals by women carrying more than one fetus.

There is a paucity of information on the metabolic effects of undernutrition of the ewe carrying multiple fetuses in late pregnancy. In the present study the effects of induction of ketosis from 132 d gestation in ewes carrying twin fetuses were compared with a control group. The ewes were well fed up to 132 d. Ketotic ewes showed a loss of condition score from 3.7 (SE 0.11) at 130 d gestation to 3.0 (SE 0.15) 10 d later after clinical recovery, compared with control twin-pregnant ewes (P < 0.01). The weight loss during the same time period was from 70.6 (SE 2.7) kg at 130 d to 64.2 (SE 2.7) kg at 140.d gestation. As expected, both groups lost weight and condition score in the first 28 d of lactation. Induction of ketosis caused a significant shortening of the gestation period to 142.8 (SE 0.7) d compared with 150 (SE 0.4) d in normal twin-pregnant ewes (P < 0.001). Ewes with induced ketosis recovered clinically and showed a normal feed intake by 3.4 (SE 0.07) d; three required treatment. Induction of ketosis resulted in reduction of hepatic uptake of bromosulphthalein (P < 0.01) and its biliary excretion (P < 0.05), metabolic clearance rate (P < 0.001), fractional clearance (P < 0.001) and 15 and 30 min retention compared with control twin-pregnant ewes. Most values had returned to normal by the first week of lactation. It is thought that in human pregnancy similar changes in bromosulphthalein clearance may be related to reduced binding sites for bromosulphthalein in the liver caused by increased circulating oestrogens. Induction of ketosis resulted in a significant hypoglycaemic (P < 0.01), ketotic (P < 0.001) state compared with well-fed twin-pregnant ewes. These changes could be correlated with the severity of the clinical signs, together with a significant rise in plasma urea (P < 0.001) and NH3 (P < 0.05) concentrations. Again, the return of most of these values to normal by the first week of lactation lends support to the reversibility of hepatic lesions caused by fatty infiltration of the liver. The severity of this condition in naturally occurring cases suggests that factors other than undernutrition may be contributory, such as the general body condition of the ewe and glucose metabolism by the liver, including the conversion of propionate to glucose.

Objective: Our purpose was to determine the amniotic fluid volume in normal diamniotic twins., Study Design: The single amniotic fluid index for both twin members, the maximum depth and width of each twin's largest pocket, were measured every 4 to 6 weeks between 15 and 40 weeks in 91 normal diamniotic twin gestations. The two-diameter pocket in each twin was determined as its largest pocket's depth multiplied by its width. Normal twin gestations were defined as those with <20% birth weight discordance, appropriate for gestational age, no fetal anomalies, delivery at > or = 37 weeks, and normal newborns. Amniotic fluid index values, depths, and two-diameter pockets were stratified into 2-week intervals and transformed into base 10 logarithms because of their nongaussian distributions. The correlations of these measurement with gestational age were evaluated. Their means and 90%, 95%, and 98% confidence intervals were determined., Results: The amniotic fluid index changed significantly with gestational age. However, depths and two-diameter pockets did not. The amniotic fluid index rose from 15 to 24 weeks, plateaued until 36 weeks, and then declined. The 90%, 95%, and 98% confidence intervals for each twin's depth were 2.4 to 7.9, 2.1 to 8.8, and 1.9 to 10 cm, respectively (mean 4.3 cm). These respective confidence intervals for each twin's two-diameter pocket were 8 to 44, 7 to 52, and 5 to 63 cm2 (mean 19 cm2). The amniotic fluid index confidence interval curves were plotted from the log (amniotic fluid index)=0.8276 + 0.01675x-0.0000001900x4, R2=0.78, p=0.002 (where x is gestational age)., Conclusion: The amniotic fluid volume in normal diamniotic twin pregnancies was established ultrasonographically. Only the amniotic fluid index changed significantly with gestational age. These findings may have significance in the clinical management of twin gestation.

Gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) and its intestinal and placental isomers were measured at between 12 and 32 weeks after the LMP in the amniotic fluid of 492 pregnancies, including 400 used to establish normal values. Three cases of trisomy 21, 2 of trisomy 18 and one case of mucoviscidosis were tested. Amniotic GGT decreased during normal pregnancies while total ALP and the intestinal isoenzyme remained stable. These intestinal enzyme levels were lowered in the presence of chromosomal abnormalities (autosomal trisomy) or mucoviscidosis. Levels of these enzymes were determined in 5 multiple pregnancies which culminated in the birth of normal infants.

The impact of an increasing fetal and placental mass on maternal glucose disposal rate (GDR) was studied in 17 pregnant women. Eleven pregnancies were singleton pregnancies, five were twin and one was a triplet pregnancy. Both the maternal fasting glucose concentration [Glc] and the total fetal and placental weight (W) were significantly correlated with an increased maternal GDR. Glucose concentration and conceptus weight were interdependent. The multiple linear regression of glucose disposal rate on glucose concentration and total weight is given by GDR = -1.573 + 0.176W + 0.932[Glc] +/- 0.24, r2 = 0.52, P < 0.01. These data are utilized to estimate the glucose utilization rate of the human conceptus at a fasting glucose concentration of 3.9 mM with a range of 10-15 mg.kg-1.min-1. Maternal GDR increases with increasing glucose concentration at a rate similar to that reported for newborn infants, consistent with a high glucose utilization by the uterus.

In litter-bearing mammals, the course of development of male and female fetuses is affected by the presence of other fetuses of the same or opposite sex located nearby within the uterus. The transport of testosterone between rat fetuses was examined by implanting a Silastic capsule containing [3H]testosterone into the amniotic sac of a fetus at either the ovarian or cervical end of a uterine horn on days 19 and 20 of pregnancy. The amount of testosterone that was recovered from the amniotic fluid of other fetuses 12 h later was determined. The amniotic fluid surrounding the adjacent fetus on the cervical side of the implanted fetus contained three times as much [3H]testosterone as did the adjacent fetus on the ovarian side, regardless of where in the uterus the implant was made. The movement of dye injected into the uterine lumen was towards the cervix. Intraluminal fluid movement may thus mediate the greater transport of [3H]testosterone towards the cervix than towards the ovary. Our findings support the hypothesis that transport of testosterone between fetuses occurs across the fetal membranes via diffusion, such that any fetus (male or female) located between male fetuses receives the greatest supplement of testosterone.