Utero-ovarian Vein Research Articles

Analysis of blood parameters and molecular endometrial markers during early reperfusion in two ovine models of uterus transplantation.

The dissection of the veins is the trickiest step of Uterine transplantation (UTx). Performing the anastomosis of a single uterine vein could bring a therapeutic benefit and simplification of surgery and serve for managing unilateral venous thromboses. The objectives of this project were to evaluate the expression of early markers of ischemia-reperfusion and to compare findings following one or two vein anastomoses. Orthotopic uterine auto-transplantations were performed on an ovine model with anastomosis of either two (group 1) or one utero-ovarian veins (group 2). Blood gases, histology and ischemia- reperfusion markers transcripts (PTGS2, IL6, IL8, SOD2, C3, BAX/BCL2 and TLR4) were analyzed as well as PTGS2 protein expression using Western Blot and fluorescence immunolocalization on endometrial biopsies after 3h of reperfusion. Ten ewes were included in the experimentation, 4 were in group1, 3 in group 2, the others being sham operated controls. No significant differences were observed between the two phenotypes. Based on these results, the anastomosis of one single uterine vein appears to be an approach consistent with short-term graft survival. Further experiments will be needed to confirm the reliability of this approach, especially the long-term follow-up of the uterine graft including its ability to support gestation to term.

Human uterine vasculature with respect to uterus transplantation: A comprehensive review.

Due to the novelty of uterus transplantation, data on preferable inflow and outflow of the graft are limited. This paper reviews the technique, type of vessels and the outcome. A systematic search of the PubMed database was conducted. We extracted and analyzed data on the arteries and veins utilized, types of anastomosis, types of donors, complications and the outcome. Thirty eight sources reported 51 human uterine transplantations, 10 graft thromboses and 25 live births. Inflow was established with two uterine arteries (UA) with/without the anterior division of the internal iliac artery in 62% (n = 31) of cases, two UA arteries with a segment/patch of the internal iliac artery in 34% (n = 17) of cases or two UA with a conduit in 4% of cases (n = 2). Both cases with a conduit developed thrombosis (n = 2). Arterial thrombosis/ischemia developed in 8 of the 51 cases. In 50% of cases with arterial thrombosis, atherosclerosis was identified as a possible cause. Outflow was established by two internal iliac veins with patches/segments in 27.5% of cases (n = 14) followed by two utero-ovarian veins in 25.5% (n = 13). Venous thrombosis occurred in 3 of the 51 cases. Uterine arteries with/without anterior division of the internal iliac artery were the most frequent arteries used for inflow and produced the highest patency rate. The presence of atherosclerosis and complex arterial reconstruction was associated with a high rate of arterial thrombosis. None of the veins utilized in the procedures appeared to be superior. There are insufficient data to draw a definite conclusion.

Meeting Report: First State-of-the-Art Meeting on Uterus Transplantation.

Meeting Report: First State-of-the-Art Meeting on Uterus Transplantation.

DUETS (Dallas UtErus Transplant Study): The role of imaging in uterus transplantation.

Objective:Uterus transplantation is rapidly becoming a viable clinical option for women with uterine-factor infertility and a desire for parenthood. Radiological imaging plays a central role in selecting the optimal living donors for uterus transplantation and serves to exclude any pathology and evaluate the uterine vasculature. The latter is the most important variable in the ultimate technical success of the uterus transplant. In this first report of imaging in the setting of uterus transplantation, we report our experience with living-donor selection, and the evolution of the imaging techniques that ultimately allowed a significant improvement in donor selection and transplant outcome. We also suggest a framework for preoperative imaging in uterus transplantation.Methods:Between 2016 and 2018, 27 potential living donors were evaluated by imaging prior to uterine donation for uterus transplantation. Predonation imaging included a screening chest radiograph, dual-phase computed tomography (CT) angiograms of the abdomen and pelvis in the arterial and venous phases and pelvic sonography with Doppler. Seventeen potential donors additionally underwent multiphasic pelvic MR angiograms. The imaging performed was meant to display features of the vascular anatomy relevant for uterus transplantation.Results:Out of the 27 potential live donors who were evaluated by imaging, 9 eventually donated their uterus for transplantation. The most frequent reason for exclusion was suboptimal quality of the vessels (33%), including small uterine arteries, the presence of atherosclerosis or small size/poor quality of the uterine or utero-ovarian veins, or both. The next most common reason was voluntary patient withdrawal or failure to complete the evaluation process (28%). Three potential donors (16.6%) were rejected for uterine factors, fibroids, and/or adenomyosis. Other reasons for donor rejection included ABO incompatibility and unfavorable psychological evaluation.Conclusion:Diagnostic imaging plays a crucial role in selecting appropriate potential donors, screening prospective recipients, planning the graft procedure, and following up on any graft or nongraft-related complications in both the donor and recipient after the transplantation procedure is performed. Contrast-enhanced CT and MR angiographies have complementary roles, especially when evaluating the donor for adequacy of the arterial and venous supply to the uterine graft and the experience gained from our series indicates that the inclusion of both modalities contributed directly to successful uterus transplant graft survival by selecting patients with favorable arterial and venous vasculature.

Novel Anastomotic Technique for Uterine Transplant Using Utero-ovarian Veins for Venous Drainage and Internal Iliac Arteries for Perfusion in Two Laparoscopically Harvested Uteri

Study ObjectiveTo evaluate 2 cases of uterine transplant surgery that used utero-ovarian veins as outflow channels, internal iliac arteries for perfusion, and the organ harvest surgery performed laparoscopically. DesignCase study (Canadian Task Force Classification III). SettingAn urban, private, tertiary care hospital. PatientsTwo patients, ages 30 and 24years, diagnosed with absolute uterine factor infertility secondary to Mayer-Rokitansky-Küster-Hauser syndrome underwent related living donor uterine transplants; donors were their mothers with normal menses. InterventionsRetrieval of organs through minilaparotomy and laparoscopic harvest of donor internal iliac arteries and ovarian veins. Measurements and Main ResultsAnastomosis was completed with bilateral donor internal iliac arteries to recipient internal iliac arteries in an end-to-end manner and with bilateral donor ovarian veins to recipient external iliac veins in an end-to-side manner. The lengths of utero-ovarian veins of both donors were 11 and 11cm on both sides; the lengths of the internal iliac arteries of both donors were 10 and 7.5cm on the left side and 10 and 6cm on the right side. The operative times for harvest surgery, bench surgery and transplant surgery were 2:40 and 3:20 hours, 34:32 and 33:30 min and 4:00 and 4:30 hours respectively for recipients 1 and 2. Daily postoperative uterine Doppler was completed through day 8 and then every other day and showed good intrauterine blood flow (i.e., low resistance arcuate vessel flow; resistance index < .5). Cervical biopsies on postoperative days 7 and 14 showed no evidence of rejection in either recipient. Both recipients started menstruating within 2 months of surgery. ConclusionBy using ovarian veins as outflow channels, the challenges involved in dissection along the internal iliac vein are avoided, and harvesting the donor internal iliac artery reduces the tension on vascular anastomosis. The selection of vessels to be harvested could make the technique reproducible, although larger studies are warranted to confirm results.

Team preparation for human uterus transplantation: Autologous transplantation in sheep model.

We performed autologous uterus transplantation using the living-sheep donor model for team preparation before human uterine transplantation. Five sequential operations (in 3 ewes) were prospectively conducted. Surgical technique included uterus retrieval, graft preparation, and uterus transplantation. Anastomoses were performed at the level of the external iliac. At 3-week follow-up, the uterus and anastomoses were checked for strictures and thrombosis. Two successful auto-transplantations were made, and one failed because of undeveloped uterine arteries (< 1mm in diameter). In the first two ewes, we identified and used a deep, separate uterine vein, which was not described in other publications. In the third ewe, we used the utero-ovarian vein. The team was able to perform safe dissection and auto-transplantation, with no signs of strictures or thrombosis after 3weeks. Cold ischemic time was 60minutes, and warm ischemic time was between 40 and 60minutes, with no need for re-anastomoses. We noticed that using the deep uterine vein in the sheep model can anatomically simulate better the human uterine vein and the difficulty to approach it. To avoid using unsuitable vessels for anastomoses, the uterine transplantation protocol in humans should include imaging of the donor's uterine vessels.

Uterus Transplantation Model in Sheep With Heterotopic Whole Graft and Aorta and Cava Anastomoses

Uterine transplantation in the sheep model has been described as a partial or whole orthotopic graft from a living donor with vascular anastomoses. As an alternative to surrogate pregnancy or adoption uterus transplantation might be indicated for cases of infertility of uterine origin. The main complications might be rejection and thrombosis. The objective of this work was to develop a model of whole uterus transplantation that was applicable to the human setting, using grafts obtained from brain-dead donors, and suitable for immunologic and viability follow-up with a reduced risk of thrombosis. Two donors and 1 recipient were operated. The first graft was used for an anatomic study; the second was used for transplantation. The donor operation consisted of an en bloc harvest of the uterus, adnexa, and proximal vagina with the distal aorta and cava. After harvest the donor sheep was humanely killed. In the recipient ewe, heterotopic implantation was performed in the lower abdomen. An End-to-side anastomoses of aorta and cava were performed below the recipient's renal vessels. A cutaneous vaginal stoma was performed in the right lower quadrant. The recipient ewe was humanely killed for an autopsy study. The anatomy of uterine veins of the ewe differs from the human. The uterine and ovarian veins join, forming the utero-ovarian vein, which drains at the confluence of the common iliac to the cava. En bloc harvesting allows for rapid graft preparation, with vascular cuffs easily anastomosed with a low risk of thrombosis. The vaginal stoma seems appropriate to facilitate follow-up and graft biopsy. This approach can be a suitable experimental model applicable to humans using grafts from brain-dead donors.

Spontaneous Rupture of Uterine Vein in Twin Pregnancy

Objective. Aim of our study is to present a case of a twin pregnancy following invitro fertilization cycle complicated with hemoperitoneum at third trimester. Case. A 26-year-old nulliparous pregnant woman at 32 weeks of gestation with twin pregnancy following invitro fertilization cycle complained of abdominal pain. After 48 hours of admission, laparotomy was performed with indications of aggravated abdominal pain and decreased hemoglobin levels. Utero-ovarian vein branch rupture was detected on the right posterior side of uterus and bleeding was stopped by suturing the vein. Etiopathogenesis of the present case still remains unclear. Conclusion. Spontaneous rupture of the uterine vessels during pregnancy is a rare complication and may lead to maternal and fetal morbidity and mortality. Diagnosis and treatment are based on the clinical symptoms of acute abdominal pain and laboratory tests of hypovolemic shock signs.

Transport of Prostaglandin F2α Pulses from the Uterus to the Ovary at the Time of Luteolysis in Ruminants Is Regulated by Prostaglandin Transporter-Mediated Mechanisms

In ruminants, prostaglandin F2alpha (PGF(2alpha)) is the uterine luteolytic hormone. During luteolysis, PGF(2alpha) is synthesized and released from the endometrium in a pulsatile pattern. The unique structure of the vascular utero-ovarian plexus (UOP) allows transport of luteolytic PGF(2alpha) pulses directly from the uterus to the ovary, thus bypassing the systemic circulation. However, the underlying molecular mechanism is not known. The objective of the present study was to determine a role for PG transporter protein (PGT) in the compartmental transport of PGF(2alpha) from uterus to ovary through the UOP at the time of luteolysis using the sheep as a ruminant model. [(3)H]PGF(2alpha), with or without a PGT inhibitor, was infused into UOP, and PGF(2alpha) transport and PGT protein expression were determined. Results indicate that PGT protein is expressed in tunica intima, tunica media, and tunica adventitia of the utero-ovarian vein and the ovarian artery of the UOP, and the expression levels are higher on d 10-15 compared with d 3-6 of the estrous cycle. Pharmacological inhibition of PGT prevented transport of exogenous [(3)H]PGF(2alpha) as well as oxytocin-induced endogenous luteolytic PGF(2alpha) pulse up to 80% from uterine venous blood into ovarian arterial blood through the UOP at the time of luteolysis in sheep. Taken together, these results indicate that at the time of luteolysis, transport of PGF(2alpha) from uterus to ovary through the UOP is regulated by PGT-mediated mechanisms. These findings also suggest that impaired PGT-mediated transport of PGF(2alpha) from the utero-ovarian vein into the ovarian artery could adversely influence luteolysis and thus affect fertility in ruminants.

The lack of relationship between progesterone level in utero-ovarian vein and the number of corpora lutea in the pigs.

Progesterone (P4) level in blood taken from both left and right utero-ovarian vein of cyclic sows was determined and number of corpora lutea in adjacent ovaries was recorded. No relationship between these two parameters has been shown.

Evidence for Relaxin and Progesterone Synchronous Secretion on Days 13 to 17 of the Oestrous Cycle in Sows1)

Concentrations of relaxin in both the utero-ovarian vein (UOV) and jugular vein (JV) as well as those of progesterone and prostaglandin F2 alpha in the UOV were studied on Days 13-17 of the oestrous cycle in sows. Mean relaxin plasma concentrations in the UOV and JV were correlated (r = 0.55; P less than 0.001) and were significantly higher (P less than 0.01) in the UOV (1.67 +/- 0.07 ng/ml), than in the JV (0.59 +/- 0.1 ng/ml). The great similarity between relaxin and progesterone profiles was ascertained (r = 0.57; P less than 0.001). The steep decrease of progesterone plasma concentration on the day of luteolysis was observed together with synchronous relaxin concentration decline. A significant correlation between relaxin and PGF2 alpha plasma concentration was demonstrated one day before luteolysis (r = 0.41; P less than 0.001).

Uterine mechanisms of ipsilateral directed spermatozoa transport: Evidence for a contribution of the utero-ovarian countercurrent system

Objective Spermatozoa transport into uterus and fallopian tubes is directed to the side of the dominant follicle and seems to be controlled by the ipsilateral ovary. The objective of this study was to evaluate the temperature in the fallopian tubes as well as the concentrations of estradiol and progesterone in the utero-ovarian veins draining the ipsilateral ovary and compare these to the contralateral side of the uterus. Study design A prospective clinical study. Setting Academic-assisted reproductive technology program. Subjects Temperature was measured in both oviducts of 10 patients each in the early phase as well as during the late follicular phase during the course of examination of tubal patency and function. Blood samples of the ovarian veins were obtained during hysterectomy in 10 premenopausal patients with regular menstrual cycles. Five of the women were in the early follicular phase and 5 were in the late follicular phase. Results Late follicular phase temperature as well as concentrations of estradiol and progesterone were significantly higher in the ipsilateral tube and the utero-ovarian veins draining the ipsilateral ovary as compared to the contralateral side. No such differences were found during the early follicular phase of the cycle. Conclusions These data support our view that the uterus and fallopian tubes during the late follicular phase immediately before ovulation are composed of two functional units with different functional properties acting as a peristaltic pump resulting in increased transport of spermatozoa into the oviduct ipsilateral to the ovary bearing the dominant follicle and that this effect is mediated in part by the utero-ovarian countercurrent system.

Insuffisance veineuse pelvipérinéale et varices des membres inférieurs. Diagnostic par écho-doppler et traitement endoluminal chez trente patientes

Pelvic congestion is the most commonly recognized consequence of pelvi-perineal venous insufficiency (PPVI). The implication of PPVI in the generation of varicoceles and varicose veins of the lower limbs arising from perineal varices has not been studied specifically. We report our duplex-Doppler findings in a series of 150 women seen over a period of 36 months. All patients presented perineal varices and, more specifically, utero-ovarian venous reflux. Thirty women were retained for phlebography then treatment by embolization. All of the left utero-ovarian veins were incontinent, the right utero-ovarian vein could not be explored in one patient, and only three of the eight opacified veins were incontinent. Twenty-two patients presented an associated incontinence of the hypogastric branch (7 left, 15 bilateral). Embolization was performed on 29 left utero-ovarian veins and one right vein with, as complementary treatment, embolization of 15 hypogastric branches, six during a second session. There were no serious complications. At six months (range 2-20 months), no improvement was noted in 10% of the patients, symptoms had improved or the varices had diminished in 59%, and all symptoms had disappeared in 31%. A duplex-Doppler exploration should be performed to search for perineal involvement in all patients presenting varicose veins of the lower limbs. The good preliminary results obtained after embolization of the pelvic veins, and particularly the left utero-ovarian vein, suggests this therapeutic approach should be pursued. The long-term effect should be assessed because of the plexiform nature of recurrent venous disorders.

Changes in prostaglandin production and ovarian function in gilts during endometritis induced by Escherichia coli infection

The aim of this study was to determine the prostaglandins (PGs) production and ovarian function in gilts after intrauterine infusions of 10 6 and 10 9 colony-forming units (cfu)/ml of Escherichia coli ( E. coli). In Experiments 1 and 2, 30 ml of saline or 30 ml of E. coli suspension containing 10 6 or 10 9 cfu/ml, were infused once into each uterine horn in three groups of gilts on day 3 of the estrous cycle, respectively. In Experiment 1, 17 days after treatment it was revealed that inoculation of E. coli 10 9 cfu/ml induced severe acute or subacute endometritis while 10 6 cfu of E. coli evoked moderate acute endometritis or resulted in no inflammatory changes. In the gilts receiving 10 9 cfu/ml of E. coli, the concentration of 13,14-dihydro-15-keto-PGF 2α in blood from the jugular vein was elevated ( P < 0.05–0.001) compared to concentration in the gilts inoculated with 10 6 cfu on days 8–17 after treatment. Both the E. coli-treated groups had a lower ( P < 0.05, P < 0.01) progesterone plasma level from days 10 to 14 after administration than the control group. On day 17 of the study, infusion of E. coli 10 9 cfu/ml, in comparison to 10 6 cfu, resulted in the greater ( P < 0.001) content of PGE 2 in the myometrium. The content of both PGs in the endometrium as well as PGF 2α in the myometrium of gilts-treated with 10 9 cfu/ml of E. coli was lower ( P < 0.001) than in gilts-treated with 10 6 cfu of bacteria. Newly formed corpora lutea were found in the gilts infused with 10 6, but not those infused with 10 9 cfu/ml of E. coli on day 17 after infusion. On day 8 of the study (Experiment 2), the blood from utero-ovarian vein of the gilts-treated with 10 9 cfu/ml of bacteria had a higher ( P < 0.05) PGF 2α level and lower ( P < 0.001) PGE 2 level than following infusion of E. coli 10 6 cfu/ml. Also on day 8 of the study, the content of PGE 2 in the endometrium, both the PGs in the myometrium as well as cyclooxygenase-2 in the endometrium and myometrium was greater ( P < 0.01, P < 0.001) after applying 10 9 cfu/ml than 10 6 cfu/ml of E. coli. These results indicate that intrauterine infusions of 10 6 or 10 9 cfu/ml of E. coli lead to the development of inflammatory states of different intensities which is connected with different PGF 2α and PGE 2 production and function of ovaries.

Changes in the expression of prostaglandin E and F synthases at induced and spontaneous labour onset in the sheep.

The differential production of prostaglandin (PG) F(2 alpha) and PGE(2) within the uterine compartment may play a role in controlling myometrial contraction. We hypothesized that the enzymes downstream of PG endoperoxide synthase-2 (PGHS-2) determine the ratio of PGF(2 alpha) and PGE(2) in the utero-ovarian vein plasma and the time of normal and preterm labour onset. The aim of this study was to simultaneously determine the expression of PGF and PGE synthases (PGFS and PGES) in gestational tissues at spontaneous and induced-preterm labour in sheep. Myometrial, endometrial and placental tissue were obtained from ewes in dexamethasone-induced preterm labour, age-matched control ewes, and ewes in spontaneous term labour for analysis of mRNA expression by real-time PCR. PGFS mRNA expression was significantly increased following dexamethasone-induced and spontaneous labour onset in placentome (P<0.01) but was unchanged in the myometrium and endometrium. In contrast, PGES mRNA expression remained unchanged or decreased. PGHS-2 mRNA expression was increased in all tissues examined in both dexamethasone-induced and spontaneous labour (P<0.001). Plasma PGE(2) and PGF(2 alpha) concentrations rose in both dexamethasone-induced and spontaneous labour with the ratio of PGF(2 alpha):PGE(2) increased with labour onset (P<0.05). These results are consistent with the hypothesis that the increased expression, of PGFS is responsible for the increased PGF(2 alpha):PGE(2) ratio and this, together with increased PGHS-2 expression, accounts for myometrial activity at labour onset. The findings point to PGFS expression as a key factor in regulating the uterotonic process in the sheep.

Rotura espontánea de los vasos uteroováricos en el posparto

Spontaneous rupture of utero-ovarian veins occurring during pregnancy or in the peripartal period is generally considered to be a medical curiosity (approximately 100 cases reported), rarely mentioned in obstetric textbooks.It is nevertheless a dramatic cause of maternal and/or fetal mortality.The available statistics are the following: 60% of cases are directly related to labour, and 50% occur in primigravidas; when the rupture is associated with labour, mortality is 40%. Occurring out of labour, mortality is approximately 10%. Perinatal mortality remains high at 30%; in 75% of cases, the broad ligament is the site of rupture (in many cases the site of rupture is not found, either at laparotomy or autopsy).We report the case of a patient who developed ovarian vein rupture on the 2nd postpartum day.

Spontaneous Rupture of the Uterine Artery in a Non-Pregnant Woman

Spontaneous rupture of the uterine artery is a rare event. Our Medline search revealed only 4 cases all of which occurred during pregnancy or puerperium. These haemorrhagic events present as acute abdomen with haemodynamic instability. In this report we describe a case of a non-pregnant woman with spontaneous rupture of the uterine artery. The aetiology of the condition is largely speculative. (excerpt)

Secretion of oxytocin in pregnant and parturient cows: corpus luteum may contribute to plasma oxytocin at term.

Plasma oxytocin (OT) concentrations were determined in 14 late-pregnant and parturient Angus-Hereford cows. Jugular and utero-ovarian veins were cannulated for simultaneous withdrawal of blood samples. Samples were collected at 10-min intervals for 6 h once weekly beginning 60-14 days before the date of expected delivery (group 1), or daily 3-7 days before the due date (group 2). In a third group, samples were collected at 15-min intervals every other day for 12 h beginning 1 wk before calving. Basal levels of OT were low, the overall mean for both veins was 0.46 +/- 0.03 microU/ml until a week before parturition, and then increased to 0.77 +/- 0.1 microU/ml (P < 0.02). Spurts of OT occurred intermittently on all days. Interpeak intervals averaged 71.0 +/- 10.7 min until Day -14, and from Day -14 to Day -1 the intervals were 44.0 +/- 5.3 min (P < 0.05). From Day -60 to Day -25 the amplitudes of OT peaks were low and similar in both veins (mean 1.37 +/- 0.1 microU/ml). From Day -14 to Day -1 the peak amplitudes were 3.6 +/- 0.4 microU/ml on average (P < 0.02). During the last 2 wk the utero-ovarian peak of OT was frequently higher than the peripheral peak. In addition, a number of spurts were observed in the utero-ovarian vein only (solo peaks). On the day of parturition during the first stage of labor, peak amplitudes had increased to 7.3 +/- 2.0 microU/ml, and the interpeak intervals had become shorter than before labor (mean 25.1 +/- 2.6 min). A large surge of OT initiated the expulsive stage of labor. Basal levels rose to 43.1 +/- 16 microU/ml and 38.7 +/- 12.6 microU/ml, and peak levels to 77.4 +/- 19.1 microU/ml and 91.6 +/- 21 microU/ml in the jugular and utero-ovarian veins, respectively. Interpeak intervals had decreased to 17.2 +/- 3.3 min (P < 0.05). Oxytocin levels remained high after delivery of the calf until the placenta was expelled. The posterior pituitary was the source of circulating OT during most of gestation and labor, but the solo peaks observed during late gestation in the utero-ovarian vein were probably of luteal origin or possibly of caruncular origin, because near term, both tissues express OT mRNA. Fetal posterior pituitary is another possible source for these peaks. Our conclusions are that during bovine pregnancy, low amplitude spurts of OT are secreted intermittently; near term, both the frequency and peak amplitude of the spurts increase; and during labor, a dramatic increase in plasma OT precedes the expulsion of the calf. The main source of OT is the posterior pituitary, but near term, a utero-ovarian source secretes additional OT into the systemic circulation.

Spontaneous rupture of a utero-ovarian vein during pregnancy

Atraumatic rupture of a utero-ovarian vein during pregnancy is a potentially lethal complication that is likely to be misdiagnosed because of its rarity. We report the case of a 31-year-old woman at 25 weeks’ gestation who had an acute abdomen and shock. (Am J Obstet Gynecol 2001;184:241-2.)

Inhibition of premature labor in sheep by a combined treatment of nimesulide, a prostaglandin synthase type 2 inhibitor, and atosiban, an oxytocin receptor antagonist

Objective: The aim of this study was to compare the effects of the selective prostaglandin synthase type 2 inhibitor nimesulide, alone or in combination with the oxytocin receptor antagonist atosiban, on the progression of glucocorticoid-induced premature labor in sheep. Effects on circulating maternal and fetal prostaglandin concentrations and on fetal well-being were also examined. Study Design: Premature labor was induced in ewes with long-term catheterized fetuses by infusion of dexamethasone (1 mg/d) starting at 138 ± 1 days’ gestation. Ewes also received an infusion of either nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 5), nimesulide alone (20.0 mg/kg per day; n = 5), or vehicle only (n = 9). Plasma 13,14-dihydro-15-keto-prostaglandin F2α and prostaglandin E2 concentrations were measured before and during infusions in plasma samples obtained from the maternal and fetal carotid arteries and the utero-ovarian vein. Results: No fetuses from ewes treated with nimesulide and atosiban were delivered during treatment. These animals were killed electively 98.0 ± 6.8 hours after the commencement of dexamethasone induction. This was significantly longer than the delivery times for those ewes treated with nimesulide alone (71.2 ± 3.9 hours; n = 5) and for vehicle-treated ewes (51.4 ± 1.7 hours; n = 9). Both maternal and fetal plasma 13,14-dihydro-15-keto-prostaglandin F2α and prostaglandin E2 concentrations in nimesulide and atosiban–treated ewes and in nimesulide-treated ewes decreased during treatment. In contrast, vehicle-treated ewes showed a significant increase in maternal and fetal plasma 13,14-dihydro-15-keto-prostaglandin F2α and prostaglandin E2 concentrations during dexamethasone induction. Uterine electromyographic activity observed in nimesulide and atosiban–treated ewes was significantly suppressed with respect to activities in both vehicle- and nimesulide-treated ewes during the treatment period. All fetuses were alive at delivery or scheduled death. Conclusions: These results indicate that the combination of an inhibitor of prostaglandin endoperoxidase H synthase type 2 with an oxytocin receptor antagonist is more effective in inhibition of preterm labor than is treatment with a prostaglandin endoperoxidase H synthase type 2 inhibitor alone. The clinical use of atosiban to prevent the oxytocin-stimulated increase in uterine activity associated with labor in combination with nimesulide may permit reduction of the dose of nimesulide used to a level that has minimal impact on fetal well-being. (Am J Obstet Gynecol 2000;183:649-57.)