Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

[This corrects the article DOI: 10.1055/a-2044-0203.].

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

[This corrects the article DOI: 10.1055/a-2044-0345.].

The Posttraumatic Impact of Recurrent Pregnancy Loss in Both Women and Men.

Introduction Recurrent pregnancy loss is usually associated with significant psychological distress for both partners of the couple. It may act as a traumatic experience resulting in a posttraumatic stress disorder. The object of this study is to examine the posttraumatic impact of recurrent pregnancy loss on men and women and their interdependencies. Methods Cross-sectional study. All couples referred to the special unit for recurrent pregnancy loss between March 2019 and October 2020 were asked to participate with a sample size of 105 couples and 17 women. They were invited to complete a questionnaire package estimating the prevalence of posttraumatic stress, with anxiety, depression, lack of social support and dysfunctional coping strategies as contributing risk factors. Couple data were analysed with the Actor Partner Interdependence Model, taking the couple as a dyad. Results The response rate was 82.3 percent, with posttraumatic stress being measured in 13.7% of the women versus 3.9% of the men (p = 0.017). For women, number of curettages, controlled for the number of losses, correlated with the severity of posttraumatic stress (p < 0.05). Higher levels of anxiety, depression and lack of social support in women correlated positively with posttraumatic stress in their partners. The men's coping strategy "trivialization and wishful thinking" as well as "avoidance" correlated with more severe posttraumatic stress in the female partners (both p < 0.05). Conclusion The posttraumatic risks within a couple with recurrent pregnancy loss are interdependent. Recurrent pregnancy loss clinics should assess posttraumatic risks of both partners in their routine diagnostic process.

17-Hydroxyprogesterone Caproate for the Prevention of Recurrent Preterm Birth - A Systematic Review and Meta-analysis Taking into Account the PROLONG Trial.

Background Prior spontaneous preterm birth is a strong risk factor for the recurrence of spontaneous preterm birth in a subsequent pregnancy and has been evaluated in prevention studies using progesterone (natural progesterone administered orally or vaginally, and 17-hydroxyprogesterone caproate [17-OHPC]) as a selection criterion. Based on the findings of a randomized, placebo-controlled study, 17-OHPC was approved for use in 2011 by the Food and Drug Administration in the USA for the prevention of recurrent preterm birth. The approval was granted with qualification that a subsequent confirmatory study would need to be carried out, the results of which have just been published (PROLONG trial). Method A systematic literature search for the period from 1970 to April 2020 using the search terms "preterm birth" and "17-OHPC" or "progesterone" was carried out. Only randomized, placebo-controlled studies of women with singleton pregnancies who received 17-OHPC to prevent recurrent preterm birth were included in the subsequent meta-analysis. The relative risk and associated 95% confidence intervals were calculated. The heterogeneity between studies was evaluated with I 2 statistics. Results In addition to the original study used for the approval and the PROLONG trial, only one other study was found which met the inclusion criteria (total number of patients: 2221). With considerable heterogeneity between the studies, particularly with respect to the risk factors for preterm birth, the comparison between 17-OHPC and placebo showed no significant reduction in preterm birth rates before 37, 35 and 32 weeks of gestation and no significant differences with regard to the prevalence of miscarriage before 20 weeks of gestation or fetal deaths (antepartum or intrapartum) after 20 weeks of gestation and neonatal morbidity. Conclusion Based on the currently available data, 17-OHPC cannot be recommended for the prevention of recurrent preterm birth. Further randomized, placebo-controlled studies with clearly defined, comparable risk factors are required to identify the group of pregnant women which could benefit from the use of 17-OHPC to prevent preterm birth.

Maternal smoking as an independent risk factor for the development of severe retinopathy of prematurity in very preterm infants.

BACKGROUND/OBJECTIVES: Retinopathy of prematurity (ROP) is a severe neonatal complication potentially leading to visual impairment and blindness. Known risk factors include preterm birth, low birth weight and respiratory support. Limited and contradictory data exist on the risk of maternal smoking during pregnancy on the development of ROP. This study aims to investigate smoking as an independent risk factor for the development of severe ROP (≥stage 3). SUBJECTS/METHODS: This is a single centre retrospective case-control study of prospectively collected clinical data of infants born before 32 weeks of gestation between 2001 and 2012 at a tertiary care university hospital. The association between maternal smoking during pregnancy and the development of severe ROP was analyzed by multivariate logistic regression. RESULTS: In total, n = 751 infants born < 32 weeks of gestation were included in this study. In total, 52.9% (n = 397) were diagnosed with ROP and 10.8% (n = 81) developed ROP ≥ stage 3. In total, 8.4% (n = 63) mothers presented with a history of smoking during pregnancy, which was associated to a higher rate of ROP (OR 2.59, 95% CI 1.10-6.12). Low gestational age, low birth weight and prolonged respiratory support were confirmed as independent risk factors for the development of severe ROP. CONCLUSIONS: To date, this is the largest study evaluating the effect of maternal smoking on the development of ROP. Maternal smoking during pregnancy is identified as an independent risk factor for the development of severe ROP in preterm infants born < 32 weeks of gestation.

Recurrent pregnancy loss: a shared stressor---couple-orientated psychological research findings.

OBJECTIVE: To compare the psychological impact of recurrent pregnancy loss (RPL) on affected men and women and to determine risk and protective factors in both partners. DESIGN: Cross-sectional study. SETTING: University-affiliated fertility center. PATIENT(S): Ninety female/male couples and 14 women. INTERVENTION(S): Participants completed a questionnaire covering psychological risk factors (ScreenIVF), experience of pregnancy losses, coping strategies, and partnership satisfaction. MAIN OUTCOME MEASURE(S): Comparison of psychological risk factors, perception of RPL, and coping strategies between both partners and analysis of the influence of risk and protective factors. RESULT(S): In the ScreenIVF, 47.7% of women versus 19.1% of men showed a risk for anxiety, 51.7% versus 19.1% a risk for depression, and 28.1% versus 30.7% a risk for limited social support. The use of avoiding coping styles seems to be less favorable with regard to the psychological risk than active strategies. Having a child together and a satisfying partnership correlated with a lower risk for depression. Sharing the experience of RPL with others and being in a satisfying relationship correlated with a higher social support. CONCLUSION(S): Both men and women affected by RPL show high risks for developing depression and anxiety, underlining the importance of also including the male partners. The factors of communication with others, a satisfying relationship, and already having a child together correlate with decreased psychological risks. We advocate for health care professionals to implement screening for anxiety, depression, and social support for both partners and support them in dealing with RPL. REGISTRATION NUMBER: The study is registered in the German Clinical Trials Register (DRKS), number DRKS00014965.

Two of a kind? Immunological and clinical risk factors differ between recurrent implantation failure and recurrent miscarriage.

Recurrent miscarriage (RM) and recurrent implantation failure (RIF) are unsolved challenges in reproductive medicine. Whether RIF patients share the same risk factors as RM patients is a matter of debate. Besides clinical factors, immune alterations are discussed in both conditions. The scope of this study was to compare the prevalence of clinical and immunological risk factors in a large cohort of RM and RIF patients. Between 11/2011 and 02/2019, 613 RM and 185 RIF patients were included. A screening for anatomical malformations, endocrine, autoimmune, prothrombotic and parental chromosomal disorders was performed. The immune status was assessed using flow cytometry analysis of peripheral lymphocyte subpopulations and uterine natural killer cells (uNK cells) using immunohistochemistry. RM patients showed a higher rate of intrauterine adhesions and elevated antinuclear antibodies ≥ 1:160 (p < 0.05). A higher prevalence of submucous fibroids and increased factor VIII levels were observed in RIF patients (p < 0.05). The prevalence of an antiphospholipid syndrome (APLS) was low and did not differ between the two groups. RIF patients had higher numbers of peripheral regulatory T-cells (p < 0.05). Significant more RIF patients were diagnosed with elevated uNK cells (p < 0.05). Differences in clinical and immunological risk factors of RM and RIF patients reflect different entities. Lower Tregs in RM and higher uNK cells in RIF patients might be related to the previous exposure of the immune system to fetal cells. The low prevalence of an APLS indicates a potential overestimation of this factor in the pathophysiology of RM and RIF.

Antenatal exposure to fenoterol is not associated with the development of retinopathy of prematurity in infants born before 32 weeks of gestation.

PURPOSE: Despite safety concerns, ß2-sympathomimetics are still widely used as tocolytic agents. ß-Blockers in turn are used to treat vasculo-proliferative diseases of the newborn such as retinopathy of prematurity (ROP), which may lead to visual impairment and blindness. The scope of this study was to investigate whether antenatal exposure to the ß2-sympathomimetic fenoterol contributes to the development of ROP. METHODS: For this single-center retrospective case-control study of prospectively collected clinical data, all infants born before 32 weeks of gestation between 2001 and 2012 were included. The association of prenatal exposure to fenoterol and the development of ROP were analyzed by multivariate logistic regression. RESULTS: n = 1134 infants < 32 weeks of gestation were screened for eligibility, out of which n = 722 met the inclusion criteria. Exposure to fenoterol (n = 505) was not associated with a higher rate of ROP (OR 0.721, 95% CI 0.463-1.122). Further, duration of exposure (days) did not alter the incidence of ROP (OR 1.001, 95% CI 0.986-1.016). Frequency distribution of different ROP stages and the need for therapeutic intervention was also not affected by prenatal exposure to fenoterol. Risk factors for the development of ROP like low birth weight, low gestational age, prolonged respiratory support and multiple gestation were confirmed in our large study cohort. CONCLUSION: ß2-Sympathomimetic tocolysis does not increase the rate of ROP in premature infants born < 32 weeks of gestation. Our results render fenoterol a safe tocolytic agent regarding neonatal ROP development.

Progesterone - Effective for Tocolysis and Maintenance Treatment After Arrested Preterm Labour?: Critical Analysis of the Evidence.

Numerous experimental studies indicate that natural progesterone, through various mechanisms, exerts an inhibitory effect on uterine contractility and sensitises the myometrium for tocolytics. It was therefore appropriate to investigate the possible benefits of oral/vaginal progesterone and the synthetic progesterone derivative 17-α-hydroxyprogesterone caproate, applied intramuscularly, in clinical studies on primary tocolysis, additively to established tocolytics ("adjunctive tocolysis") and as maintenance treatment after successful tocolysis in cases of threatened preterm birth. Three studies with a small number of cases do not yield any sufficient evidence for recommending progesterone/17-α-hydroxyprogesterone caproate as primary tocolysis in women with preterm labour. There is also no evidence that progesterone or 17-α-hydroxyprogesterone caproate combined with commonly used tocolytics leads to a prolongation of pregnancy and a significant decrease in the rate of preterm birth. The data on the use of progesterone as maintenance treatment is controversial. While randomised, controlled studies with low quality showed promising results, studies with high quality did not reveal any significant differences with regard to the rate of preterm birth < 37 weeks of gestation, the latency period until delivery and in the neonatal outcome between progesterone/17-α-hydroxyprogesterone caproate and placebo or no treatment. Significant differences in the methodology, the inclusion and outcome criteria, the mode of application and the dosages of the substances as well as the inadequate statistical power as a result of low numbers of cases make interpretation and comparability of the studies difficult. Therefore, well-designed randomised, placebo-controlled, double-blind studies with uniform primary outcome criteria are needed in order to clarify whether progesterone and via which route of administration and at which dosage is of clinical benefit for patients with manifest preterm contractions and as maintenance treatment after arrested preterm labour.

Progesterone for the Prevention of Preterm Birth - an Update of Evidence-Based Indications.

The prevention and treatment of preterm birth remains one of the biggest challenges in obstetrics. Worldwide, 11% of all children are born prematurely with far-reaching consequences for the children concerned, their families and the health system. Experimental studies suggest that progesterone inhibits uterine contractions, stabilises the cervix and has immunomodulatory effects. Recent years have seen the publication of numerous clinical trials using progestogens for the prevention of preterm birth. As a result of different inclusion criteria and the use of different progestogens and their methods of administration, it is difficult to draw comparisons between these studies. A critical evaluation of the available studies was therefore carried out on the basis of a search of the literature (1956 to 09/2018). Taking into account the most recent randomised, controlled studies, the following evidence-based recommendations emerge: In asymptomatic women with singleton pregnancies and a short cervical length on ultrasound of ≤ 25 mm before 24 weeks of gestation (WG), daily administration of vaginal progesterone (200 mg capsule or 90 mg gel) up until 36 + 6 WG leads to a significant reduction in the preterm birth rate and an improvement in neonatal outcome. The latest data also suggest positive effects of treatment with progesterone in cases of twin pregnancies with a short cervical length on ultrasound of ≤ 25 mm before 24 WG. The study data for the administration of progesterone in women with singleton pregnancies with a previous preterm birth have become much more heterogeneous, however. It is not possible to make a general recommendation for this indication at present, and decisions must therefore be made on a case-by-case basis. Even if progesterone use is considered to be safe in terms of possible long-term consequences, exposure should be avoided where it is not indicated. Careful patient selection is crucial for the success of treatment.

Reducing the Risk of Preterm Birth by Ambulatory Risk Factor Management.

BACKGROUND: The preterm birth rate in Germany has remained unchanged at 8-9% since 2009. Preterm birth is the most common cause of neonatal morbidity and mortality. In the absence of a causal treatment, it is important to lower the risk of preterm birth by preventive measures in prenatal outpatient care. METHODS: This review is based on pertinent publications from the years 2000-2019 that were retrieved by a selective search in PubMed. RESULTS: The clinical risk factors for preterm birth-known mainly from retrospective cohort studies-include previous preterm birth (adjusted odds ratio [aOR]: 3.6), multiple pregnancy (relative risk [RR]: 7.7), nicotine consumption (aOR: 1.7), and a short uterine cervix, i.e., <25 mm in the second trimester (aOR: 6.9). In women with a short cervix, vaginally administered progesterone significantly lowers the preterm birth rate (22.5% vs. 14.1% for birth before 33 weeks of gestation, RR: 0.62; 95% confidence interval [0.47; 0.81]). Nicotine abstinence is associated with a lower pre- term birth rate as well (aOR: 0.91; [0.88; 0,.94]), while working more than 40 hours per week (aOR: 1.25; [1,.01; 1,.54]) and heavy lifting during pregnancy (hazard ratio [HR]: 1.43; [1.13; 1.80]) are associated with a higher preterm birth rate. Avoidance of physical exertion, or bed rest, in the face of impending preterm birth does not lower the preterm birth rate, but it does increase the risk of complications, such as thromboembolism. CONCLUSION: The meticulous assessment and elimination of treatable risk factors at the outset of ambulatory prenatal care can help lower the preterm birth rate. Further velopment of causally directed treat- ments (e.g., changes of relevant environmental and epigenetic factors).

Tocolysis with the ß2-sympathomimetic fenoterol does not increase the occurrence of infantile hemangioma in preterm and term infants.

PURPOSE: ß2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the ß2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other ß2-mimetic tocolytic agents like fenoterol. METHODS: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. RESULTS: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005). CONCLUSIONS: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different ß2-sympathomimetic tocolytic drugs.

Uterine natural killer cells in patients with idiopathic recurrent miscarriage.

PROBLEM: Uterine natural killer (uNK) cells are major players during implantation and early pregnancy. The aim of our study was to analyze uNK cell concentration in the endometrium of idiopathic recurrent miscarriage (iRM) patients and fertile controls. METHOD OF STUDY: Out of n=130 couples with ≥3 consecutive, clinical RM screened according to a standardized diagnostic protocol, n=58 patients with iRM were identified. Endometrial biopsies were investigated in patients and n=17 fertile women (controls) via immunohistochemistry. RESULTS: Compared to controls, the concentration of uNK cells was significantly higher in iRM patients (257±212 vs. 148±73 uNK cells/mm², P=.04). IRM patients showed a higher prevalence of >300 uNK cells/mm² than controls (34.5% vs. 5.9%, P=.02). In 88% of controls and 62% of iRM patients, uNK cells were detected within the range of 40-300/mm². CONCLUSION: Idiopathic recurrent miscarriage patients showed higher uNK cell levels than controls supporting the possible impact of uNK cells in the pathophysiology of miscarriage. Our cutoff levels might help to select RM patients which may benefit from immunomodulatory treatment.

Pre-Pregnancy Levels of Peripheral Natural Killer Cells as Markers for Immunomodulatory Treatment in Patients with Recurrent Miscarriage.

Immunological risk factors in patients with recurrent miscarriage (RM) are discussed controversially. Abnormalities of natural killer cells (NK) have been described in RM patients. Lipid infusions are known to modulate lymphocyte subsets. The aim of this study was to identify immune parameters that predict success of treatment with lipid infusions in RM patients with elevated NK. In sum, n = 341 couples with RM were screened for established risk factors and peripheral lymphocyte subpopulations as well as uterine NK cells. We identified n = 136 patients with ≥ 2 consecutive RM and elevated NK. So far, n = 40 RM patients with NK disorders were treated with lipid infusions starting at positive pregnancy test, every 2 weeks until 12 + 0 weeks of gestation (GW) or miscarriage. The pre-pregnancy immune diagnostics in idiopathic RM (iRM) patients with ongoing pregnancy were compared to the group with miscarriages and healthy controls (n = 15). Pre-pregnancy immune diagnostics differed significantly between the groups, with significant higher levels of peripheral NK (% and /µL) in iRM patients who miscarried again compared to controls (p = 0.0035 and p = 0.0019). Furthermore, iRM patients show lower percentages of CD3+ lymphocytes than healthy controls (p = 0.0049). In n = 22/40 (55%) patients, pregnancy is ongoing >12 + 0 GW. RM patients with very high pre-pregnancy peripheral NK (pNK) lymphocytes might not benefit from lipid infusions. Pre-pregnancy immunomodulatory treatment in RM patients might be helpful to lower pNK levels and establish an immune environment which is supportive for fetal development.

Impaired Neonatal Outcome after Emergency Cerclage Adds Controversy to Prolongation of Pregnancy.

OBJECTIVE: Emergency cervical cerclage is one of the treatment options for the reduction of preterm birth. The aim of this study is to assess neonatal outcome after cerclage with special focus on adverse effects in very low birth weight infants. STUDY DESIGN: Retrospective cohort study. Classification of cerclages in history-indicated (HIC, n = 38), ultrasound-indicated (UIC, n = 29) and emergency/ physical examination-indicated (PEIC, n = 33) cerclage. Descriptive analysis of pregnancy and neonatal outcome (admission to NICU, duration of hospitalization, respiratory outcome (intubation, CPAP, FiO2max), neonatal complications (ROP, IVH)). Statistical comparison of perinatal parameters and outcome of neonates <1500 g after cerclage with a birth weight matched control group. RESULTS: Neonates <1500 g after PEIC show significantly impaired outcome, i.e. prolonged respiratory support (total ventilation in days, CPAP, FiO2max) and higher rates of neonatal complications (IVH ≥ II, ROP ≥ 2). Placental pathologic evaluation revealed a significantly higher rate of chorioamnionitis (CAM) after PEIC. Neonates <1500 g after UIC or HIC show no significant difference in neonatal complications or CAM. CONCLUSIONS: In our study PEIC is associated with adverse neonatal outcome in infants <1500 g. The high incidence of CAM indicates a potential inflammatory factor in the pathogenesis. Large well-designed RCTs are required to give conclusive answers to the question whether to prolong or to deliver.

Assessment of parturition with cervical light-induced fluorescence and uterine electromyography.

Parturition involves increasing compliance (ripening) of the uterine cervix and activation of the myometrium. These processes take place in a different time frame. Softening and shortening of the cervix starts in midpregnancy, while myometrial activation occurs relatively close to delivery. Methods currently available to clinicians to assess cervical and myometrial changes are subjective and inaccurate, which often causes misjudgments with potentially adverse consequences. The inability to reliably diagnose true preterm labor leads to unnecessary treatments, missed opportunities to improve neonatal outcome, and inherently biased research of treatments. At term, the likelihood of cesarean delivery depends on labor management, which in turn depends on accurate assessments of cervical change and myometrial contractility. Studies from our group and others show that noninvasive measurements of light-induced fluorescence (LIF) of cervical collagen and uterine electromyography (EMG) objectively detect changes in the composition of the cervix and myometrial preparedness to labor and are more reliable than clinical observations alone. We present a conceptual model of parturition constructed on cervical LIF and uterine EMG studies. We also explore how these methodologies could be helpful with managing patients experiencing preterm contractions and with optimizing labor management protocols aimed to reduce cesarean section.

Progestin treatment for the prevention of preterm birth.

Progestin supplementation appears to be a promising approach to both preventing initiation of preterm labor and treating it once it is already established, given the role of progesterone in maintaining pregnancy, as well as support from basic and clinical research. Progesterone and 17α-hydroxyprogesterone acetate slow the process of cervical ripening, and this is the rationale for prophylactic long-term progestin supplementation mostly studied so far. However, progesterone (but not 17α-hydroxyprogesterone acetate) also inhibits myometrial activity even after the cervix has already ripened. Moreover, these effects depend greatly on the vehicle used and the route of administration. Understanding different mechanisms of action, as well as the importance of progestin formulation, vehicle and route of administration, is the key to finding the optimal progestin treatment for prevention of preterm birth.

A novel optical method to assess cervical changes during pregnancy and use to evaluate the effects of progestins on term and preterm labor.

OBJECTIVE: The purpose of this study was to determine whether optical methods can estimate cervix function during pregnancy and whether progestins modify this process. STUDY DESIGN: Photos of the external cervix of timed-pregnant rats were taken every other day from day 13 until postpartum day 5 after daily treatments with vehicle (controls) or progestin treatments (progesterone, subcutaneously or vaginally; 17-alpha-hydroxyprogesterone caproate [17P] and RU-486 subcutaneously, once on day 16). The surface area of the cervix was estimated from photos. RESULTS: The surface area of cervix increases throughout pregnancy and reverses after delivery in controls. In the progesterone subcutaneously or 17P subcutaneously groups, increases in surface area are lower (17P group until day 19 only; P < .05). Vaginal progesterone does not prevent surface area increases. Only the progesterone subcutaneously blocked delivery. RU-486 increases the surface area of the cervix (P < .05) during preterm delivery. CONCLUSION: An optical method is useful for quantitative assessment of the cervix and evaluation of agents that modify cervical function.

Use of uterine electromyography to diagnose term and preterm labor.

Current methodologies to assess the process of labor, such as tocodynamometry or intrauterine pressure catheters, fetal fibronectin, cervical length measurement and digital cervical examination, have several major drawbacks. They only measure the onset of labor indirectly and do not detect cellular changes characteristic of true labor. Consequently, their predictive values for term or preterm delivery are poor. Uterine contractions are a result of the electrical activity within the myometrium. Measurement of uterine electromyography (EMG) has been shown to detect contractions as accurately as the currently used methods. In addition, changes in cell excitability and coupling required for effective contractions that lead to delivery are reflected in changes of several EMG parameters. Use of uterine EMG can help to identify patients in true labor better than any other method presently employed in the clinic.

Pharmacologic actions of progestins to inhibit cervical ripening and prevent delivery depend on their properties, the route of administration, and the vehicle.

OBJECTIVE: The purpose of this study was to evaluate cervical changes and delivery at term during pregnancy in rats after various progestin treatments. STUDY DESIGN: Pregnant rats were treated by various routes and vehicles with progesterone, 17-alpha-hydroxyprogesterone caproate (17P), R5020, and RU-486. Delivery time was determined and cervical ripening was assessed in vivo by collagen light-induced fluorescence. RESULTS: The cervix is rigid in the progesterone injection, 17P, and vaginal R5020 groups vs controls. Vaginal progesterone had no effect. RU-486 treatment softened the cervix during preterm delivery. Only subcutaneous injected progesterone, R5020 (subcutaneous and vaginal), and topical progesterone in sesame and fish oil inhibits delivery. Delivery is not changed by subcutaneous injection of 17P, vaginal progesterone, oral progesterone, and topical progesterone in Replens (Crinone; Columbia Labs, Livingston, NJ). CONCLUSION: Inhibition of cervical ripening and delivery by progestins depends on many factors that include their properties, the route of administration, and the vehicle. This study suggests reasons that the present treatments for preterm labor are not efficacious.