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Objective: To identify the current and future state of the practice of reproductive medicine.Design: Cross-sectional survey.Setting: Not applicable.Patient(s): None.Intervention(s): Not applicable.Main Outcome Measure(s): The survey included 57 questions designed to assess practice patterns/metrics and professional satisfaction and morale.Result(s): A total of 336/1,100 (31%) responded, and they were 38% women, 61% men, and 76% Caucasian, with a mean age of 54. Respondents averaged 2.3 jobs and averaged 53 hours of work per week: 44% work in academia and 50% in private groups. Average practice size was 5.5, with an average of 470 fresh IVF cycles performed per year. Percent effort included 63% infertility, 10% endocrinology, 10% surgery, and 9% research. Respondents performed an average of 13 major surgeries, 69 minor surgeries, and 128 oocyte retrievals per year. A total of 60% were salaried, and 40% were equity partners. Compensation was highly skewed. Greater than 84% had a positive morale and had a positive view of the future, and 92% would again choose REI as a career. The most satisfying areas of employment were patient interactions, intellectual stimulation, interactions with colleagues, and work schedule. The least satisfying areas were work schedule and financial compensation. Training was felt to be too focused on female factor infertility and basic research with insufficient training on embryology, genetics, male factor infertility, and clinical research. In the next 5 years, 57% suggested that the need for specialists would stay the same, while 20% predicted a decrease. A total of 58% felt we are training the correct number of fellows (37% felt we are training a surplus). Compared with academia, those in private practice reported higher compensation, less major surgery, more IVF, less endocrinology, and less research. Men worked more hours, conducted more surgery and IVF cycles, and had higher compensation than women. Morale was similar across age, gender, practice type, and geography.Conclusion(s): Our subspecialty has an extremely high morale. We are a middle-aged subspecialty with disparate compensation and a focused practice. Some respondents sense a need for a change in our training, and most anticipate only mild growth in our field. [ABSTRACT FROM AUTHOR]

Well-designed and -conducted clinical trials are needed to further advance the field for reproductive medicine. However, current reporting of outcomes of trials is ambiguous and disparate. In this review it is offered that the preferred outcome for clinical trials in reproductive medicine should be live birth. Multiple births should be listed, and it should be specified whether this is multiple births per couple or multiple births per conception. The unit of measure should be women (or couples) and not cycles. The duration of exposure should also be clearly identified (i.e., treatment was one cycle, a prespecified number of cycles, or a period of time). Pregnancy loss should be specified, and the denominator should be those who conceived. Although live birth is the primary outcome, complications should be defined and reported, including multiple births and other objective markers, such as preterm delivery, small-for-gestational age, or stillbirth. [Copyright &y& Elsevier]

Early pregnancy failure is the most common complication of pregnancy, and 1% to 2% of all pregnancies will be ectopic. As one of the leading causes of maternal morbidity and mortality, diagnosing ectopic pregnancy and determining the fate of a pregnancy of unknown location are of great clinical concern. Several serum and plasma biomarkers for ectopic pregnancy have been investigated independently and in combination. The following is a review of the state of biomarker discovery and development for ectopic pregnancy and pregnancy of unknown location. [ABSTRACT FROM AUTHOR]

A biomarker can be used for early diagnosis of a disease, identification of individuals for disease prevention, as a potential drug target, or as a potential marker for a drug response. A biomarker may also limit the use of drug (and therefore costs) to the population of patients for which the drug will be safe and efficacious. A biomarker in reproduction could be used to improve assessment of exposure, identify subgroups susceptible to treatment, predict outcome, and/or differentiate subgroups with potentially different etiologies of disease. Despite many potential uses there is low participation in reproductive biology to develop molecular biomarkers, which may be directly related to the low number of new molecular entities entering clinical trials. As the number of candidate markers in reproductive medicine is increasing, it is important to understand the pathway of development from discovery to clinical utility and recognize that the vast majority of potential markers will not be clinically useful, owing to a variety of pitfalls. Extensive testing, validation, and modification needs to be performed before a biomarker is demonstrated to have clinical utility. New opportunities and partnerships exist and should hasten the development of biomarkers in reproduction. As more biomarkers are moved into practice, a better-educated biomarker consumer will enhance the possibility that biomarker(s) will realize their great potential. [ABSTRACT FROM AUTHOR]

Interrogating the association between assisted reproductive technologies (ART) and perinatal outcome is complicated but very important. This is an introduction to a series of articles that review this potential association with an eye toward etiology of risk, and what aspects of in vitro fertilization (IVF) can be modified to reduce this risk. When an association is not due to chance (i.e., statistically significant), one must also consider how the association may be affected due to bias or confounding. Despite lack of the perfect study, perinatal consequences of ART are apparent, even though the vast majority of children conceived with ART are healthy. Pregnancy after IVF is altered as evidenced by risk of preterm delivery, low birth weight among infants, and an alerted prevalence of preeclampsia. The long-term clinical implications of ART, such as childhood development and metabolism, have not been established and ongoing study is proceeding. The risk attributed to multiple births is iatrogenic and needs to be minimized. Optimizing the environment at the time a woman conceives will likely have an effect on gestation as well as the health of children. Reproduction effects health and health effects reproduction. [ABSTRACT FROM AUTHOR]

Objective: To assess a scoring system to triage women with a pregnancy of unknown location. Design: Validation of prediction rule. Setting: Multicenter study. Patient(s): Women with a pregnancy of unknown location. Intervention(s): None. Main Outcome Measure(s): Scores assigned to factors identified at clinical presentation, total score calculated to assess risk of ectopic pregnancy (EP) in women with a pregnancy of unknown location, and a proposed three-tiered clinical action plan. Result(s): The cohort of 1,400 women (284 ectopic pregnancies, 759 miscarriages, and 357 intrauterine pregnancies) was more diverse than the original cohort used to develop the decision rule. The recommendations of the action plan were low risk, intermediate risk, and high risk; the recommendation based on the model score was compared with clinical diagnosis. A total of 29.4% intrauterine pregnancies were identified for less frequent follow-up observation, and 18.4% nonviable gestations were identified for more frequent follow-up observation (to rule out an ectopic pregnancy) compared with intermediate risk (i.e., monitor in current standard fashion). For a decision of possible less frequent monitoring, the specificity was 90.8% (89.0–92.6) with negative predictive value of 79.0% (76.7–81.3). For a decision of more intense follow-up observation, the specificity was 95.0% (92.7–97.2). Test characteristics using the scoring system were replicated in the diverse validation cohort. Conclusion(s): A scoring system based on symptoms at presentation has value to stratify risk and influence the intensity of outpatient surveillance for women with pregnancy of unknown location but does not serve as a diagnostic tool. [ABSTRACT FROM AUTHOR]

The evolution of the diagnosis and management of women with an early pregnancy loss has been a success story. The mortality from ectopic pregnancy has objectively been decreased in the past few decades. However, modern management has resulted in a new set of issues. Over-interpretation of a single ultrasound, misunderstanding of the utility of serial hCG values, and inappropriate use of methotrexate can result in iatrogenic complications. Modern management has successfully improved the diagnosis of ectopic pregnancy before rupture; it should now also focus on ensuring that an intrauterine pregnancy is not interrupted as a result of diagnosis and treatment. This article reviews some of the pitfalls of the modern management of early pregnancy failure and introduces a series of articles on the subject. [ABSTRACT FROM AUTHOR]

The National Institute of Child Health and Human Development has conducted a series of vision workshops to set an ambitious but tenable broad agenda, transcending traditional organizational and disciplinary boundaries. This presentation sets forth a vision regarding how the aspects of a woman’s reproductive lifespan are interrelated, likely starting from childhood all the way to the later reproductive years. As a woman propagates, this circular interaction is then transmitted to the next generation. We need an understanding of the clinical processes, the time course, the natural history, and disruptors of these processes. With that understanding, we can then bring tools to bear to assess these issues, whether these tools are epidemiology, demography, social science, molecular biology, proteomics, genomics, or epigenomics. Our future research agenda should investigate how reproduction affects health and how health affects reproduction. [ABSTRACT FROM AUTHOR]

Objectives: To provide an overview of the studies that have evaluated the return to fertility following cessation of oral contraceptives (OCs), including recent evidence in women discontinuing extended-cycle and continuous-use regimens. Design: Comprehensive review. Patient(s): None. Intervention(s): Relevant articles were identified through a PubMed literature search (1960–2007) and a cross-reference of published data. Main Outcome Measure(s): Time to fertility following contraceptive use. Result(s): Numerous studies have demonstrated some delay in the time to conception in previous users of OCs who discontinued use in order to conceive, but this impairment appears to be temporary and typically limited to the early months following cessation of OC use. Reported 12-month conception rates in former cyclic OC users range from 72%–94% and are similar to those observed in women discontinuing intrauterine devices (71%–92%), progestin-only contraceptives (70%–95%), condoms (91%), and natural family planning (92%). There is a limited amount of data on the time to conception in women stopping extended-cycle and continuous-use OCs, but the data suggest that subsequent return to fertility is generally comparable to that of cyclic OCs. Conclusion(s): A comprehensive survey of reported data indicates that the return of fertility in former OC users (both cyclic and extended/continuous regimens) in women who stop use in order to conceive is comparable to that observed with other contraceptive methods. [Copyright &y& Elsevier]

Objective: To evaluate the association between ectopic pregnancy (EP) and clinical and historical factors among women presenting with pain and/or bleeding in early pregnancy. Design: Nested case–control study. Setting: University medical center. Patient(s): Women with symptomatic early pregnancies of unknown location presenting for care between January 1, 1990 and July 31, 1999. Intervention(s): None. Main Outcome Measure(s): Clinical and historical risk factors were compared between women with EP and women with ongoing intrauterine pregnancies or spontaneous abortions. Result(s): The following factors were associated with increased risk of EP: prior EP (odds ratio, 2.98 [95% confidence interval, 1.88–4.73] for one prior EP and 16.04 [5.39–47.72] for 2 or more), pelvic inflammatory disease history (1.5 [1.11–2.05]), pain at presentation (1.42 [1.06–1.92]), vaginal bleeding at presentation (1.42 [1.04–1.93]), and hCG of 501–2,000 mIU/mL (1.73 [1.24–2.42]). Age younger than 25 years (0.59 [0.41–0.85]) and a history of abortion were protective from EP (0.58 [0.38–0.90]). Prior nontubal pelvic surgery, past intrauterine device use, prior cesarean section, and current cervical infection demonstrated no association with EP. Conclusion(s): Evaluation of women with a symptomatic early pregnancy confirms and refutes some of the classical risk factors for EP. Prior EP is a strong risk factor, whereas pelvic inflammatory disease has an unexpected weak association. Previous abortion was found to have a negative association, whereas nontubal surgery, cesarean section, and a history of or concomitant cervical infection have no association. Knowledge of historical and clinical factors associated with EP may aid in early diagnosis. [Copyright &y& Elsevier]

: ObjectiveTo evaluate serial hormone concentrations in subjects treated with vaginally administered misoprostol for early pregnancy failure.: DesignAs part of a randomized clinical trial, serum was collected on treatment days 1, 3, 8, and 15.: SettingMulticenter clinical trial.: Patient(s)Women with a nonviable first-trimester pregnancy.: Intervention(s)Serum concentrations of human chorionic gonadotropin (hCG), progesterone, and sex hormone binding globulin (SHBG) were evaluated.: Main outcome measure(s)A logistic regression model was constructed to assess the associations of percent and complete expulsion of the gestational sac and/or successful management.: Result(s)The percent change from the day of treatment until the first follow-up visit was predictive for complete expulsion for progesterone (P) (P<.005) and hCG (P<.005), but not for SHBG. The actual value was not significantly associated with complete expulsion or successful management. A decrease (day 1–3) of 79% for both hCG and P was associated with a 90% probability of complete passage of the gestational sac. A 90% probability of successful management was noted if P decreased by 78% on day 3 or 59% on day 7, or hCG decreased by 74% on day 3 or 78% on day 7 compared with pretreatment values.: Conclusion(s)Percent change, but not absolute change, in serial hormone values are strongly associated with both the complete expulsion of the gestational sac with one dose of misoprostol and ultimate success. [Copyright &y& Elsevier]

: ObjectiveThe diagnosis of ectopic pregnancy (EP) is often confirmed at presentation (acute), but often requires serial β-hCG levels to confirm the diagnosis (chronic). The purpose of this study is to analyze whether these clinical presentations represent a spectrum of disease.: DesignThe retrospective cohort study of 452 patients diagnosed with EP at the University of Pennsylvania in the years 1990–1999.: SettingUniversity of Pennsylvania, Philadelphia, Pennsylvania.: Patient(s)Four hundred fifty-two patients diagnosed with EP. Patients diagnosed with EP were divided into two groups according to the time of diagnosis.: Main outcome measure(s)A total of 37 parameters were examined including historic and demographic factors, findings at presentation, and treatment and outcome variables.: Result(s)The two groups were similar in terms of historic EP risk factors. Multivariable analysis demonstrates that women with a chronic presentation were less likely to have received fertility medications (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.06–0.84), less likely to present with pain (OR 0.29; 95% CI 0.12–0.71), have a lower β-hCG level at presentation (9,849 mIU/mL ± 16,726 vs. 1,787 mIU/mL ± 4,717), lower chance of rupture (OR 0.19; 95% CI 0.05–0.73), and less frequently have blood type 0.: Conclusion(s)Women diagnosed with ectopic pregnancy can be categorized into two groups, those with an acute presentation and those with a chronic presentation. Differences in risk factors, presentation, and outcome may reflect differences in trophoblast viability or invasive potential. [Copyright &y& Elsevier]

Infertility has long-term effects beyond the inability to conceive. Infertility may be a harbinger of future disease and altered longevity. Understanding the mechanisms of how fertility is a window to health opens new avenues of important investigation addressing interdependent physiologic processes. Identification of healthy persons at risk for future cardiovascular disease, diabetes, or cancer could allow a change in reproductive medical care by altering long-term surveillance and reduction of risk. [ABSTRACT FROM AUTHOR]

The majority of perinatal morbidity after in vitro fertilization (IVF) is due to multiple pregnancy; however, even singleton infants are at an increased risk for adverse outcomes. We have summarized data that evaluates adverse outcomes in IVF infants and recent attempts to delineate the underlying causes of this risk. We submit that practitioners of reproductive medicine should remain at the forefront of this investigation. [Copyright &y& Elsevier]

The science of contraceptive medicine and reproductive medicine are similar. At present contraceptive medicine has moved beyond understanding the mechanism of action of steroid hormones with the introduction of many safe and effective methods. Long-acting reversible contraceptives are increasing in acceptance and providing very high efficacy. The science has pivoted toward optimization of family planning in selected high-risk populations, such as those with a high-risk of thrombosis, as well as addressing the challenge of obesity. The pipeline for male and female related methods will continue to advance the science and public health impact. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are the cornerstone of evidence-based medicine. In this series in Fertility and Sterility, several aspects of RCTs are discussed, with contributions on multicenter RCTs, different international settings, and integrity of RCTs. The present contribution deals with methodologic issues. We discuss different types of RCTs based on null hypothesis (superiority vs. noninferiority vs. equivalence) as well as frequentist versus Bayesian interpretation. We also discuss the use of RCTs in the era of personalized medicine and RCTs to address diagnostic and prognostic questions. Finally, we address the use of big data compared with the use of RCTs. [ABSTRACT FROM AUTHOR]

The probability of live birth from an in vitro fertilization (IVF) cycle is modest. Many additional treatments (add-ons) are available which promise to improve the success of IVF. This review summarizes the current evidence for common IVF add-ons which are suggested to improve endometrial receptivity. Systematic reviews of randomized controlled trials and individual trials were included. Five add-ons were included: immune therapies, endometrial scratching, endometrial receptivity array, uterine artery vasodilation, and human chorionic gonadotropin instillation. The results suggest there is no robust evidence that these add-ons are effective or safe. Many IVF add-ons are costly, consuming precious resources which may be better spent on evidence-based treatments or further IVF. Large randomized controlled trials and appropriate safety assessment should be mandatory before the introduction of IVF add-ons into routine practice. [ABSTRACT FROM AUTHOR]

The use of estrogens and progestins in reproductive medicine is widespread and has spanned decades. Often the effect is therapeutic, but sometimes its use has unintended consequences. In this Views and Reviews, old and new indications for the use of ovarian sex steroids are examined with attention to updating knowledge, breaking bad habits, and providing evidence for use (or nonuse). [ABSTRACT FROM AUTHOR]

The rationale to freeze all embryos to avoid transfer into a supraphysiologic environment to improve safety and efficacy is compelling, but not yet proven. How do we decide? [ABSTRACT FROM AUTHOR]

Objective: To determine if very early serum hCG, a marker of trophoblast differentiation, is associated with adverse perinatal outcomes in singleton pregnancies.Design: Retrospective cohort study.Setting: University fertility program.Patient(s): A total of 360 singleton IVF live births.Intervention(s): Serial hCG measurements were used to determine the within-woman slope for hCG (hCG rise).Main Outcomes Measure(s): Primary outcomes included birth weight and gestational age at delivery. Statistical comparisons used t test, chi-square test, and linear and logistic regressions as appropriate.Result(s): hCG rise was positively associated with birth weight but not gestational age at delivery. Infant sex, gestational age, and type of embryo transfer (fresh vs. frozen/thawed) were significantly associated with birth weight and confounded the associations of interest. hCG rise was slower among subjects delivering an infant with low birth weight (slope 0.386 ± 0.05 vs. 0.407 ± 0.06) or small for gestational age (slope 0.371 ± 0.07 vs. 0.406 ± 0.06). Analysis of hCG rise by quartile showed that, compared with the first quartile (slowest), subjects with a rate of hCG rise in the fourth quartile (fastest) had a significantly decreased risk of delivering an infant of low birth weight. No relationship was noted between hCG rise and hypertensive disorders of pregnancy.Conclusion(s): Slower very early first-trimester hCG rise is associated with low birth weight but not gestational age at delivery among singleton IVF conceptions. The rate of increase in serum hCG may reflect early trophoblast differentiation and placentation and, possibly, may predict subsequent development. [ABSTRACT FROM AUTHOR]

The trend toward a decline in the percentage of women with infertility in the United States appears real. While the factors associated with this trend are likely many, complex, and interrelated, we cannot overlook the positive impact of those individuals who practice in the field of reproductive medicine. [Copyright &y& Elsevier]

The hypothesis that bacteria in the uterus may be detrimental to an embryo is very thought provoking. The data, however, do not yet support that this is a clinically relevant issue. [Copyright &y& Elsevier]

Three-dimensional imaging of the human vagina demonstrates that the cross section can be a “W,” rather than an “H,” and that intravaginal gel can ascend into the endocervix and presumably into the endometrium. [Copyright &y& Elsevier]

To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment. International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management. A systematic review without meta-analysis of studies published in English from January 2015 to May 2022. Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon—occurring in <5% of couples with infertility—and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence. True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age). Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement. [ABSTRACT FROM AUTHOR]

To assess the benefit of frozen vs. fresh elective single embryo transfer using traditional and novel methods of controlling for confounding. Retrospective cohort study using data from the National Assisted Reproductive Technology Surveillance System. Not applicable. A total of 44,750 women aged 20–35 years undergoing their first lifetime oocyte retrieval and embryo transfer in 2016–2017, who had ≥4 embryos cryopreserved. Fresh elective single embryo transfer and frozen elective single embryo transfer. The primary outcome was a singleton live birth. Secondary outcomes included rates of total live birth (singleton plus multiple gestations), twin live birth, clinical intrauterine gestation, total pregnancy loss, biochemical pregnancy, and ectopic pregnancy. Outcomes for infants included gestational age at delivery, birth weight, and being small for gestational age. The eligibility criteria were met by 6,324 fresh and 2,318 frozen cycles. Patients undergoing fresh and frozen transfer had comparable mean age (30.69 [standard deviation {SD} 0.08] years vs. 31.06 [SD 0.08] years) and body mass index (24.76 [SD 0.20] vs. 25.65 [SD 0.15]); however, women in the frozen cohort created more embryos (8.1 [SD 0.12] vs. 6.8 [SD 0.08]). Singleton live birth rates in the fresh vs. frozen groups were 51.4% vs. 48.8% (risk ratio 1.05; 95% confidence interval [CI], 1.00–1.10). After adjustment with a log-linear regression model and propensity score analysis, the difference in singleton live birth rates remained nonsignificant (adjusted risk ratio, 1.05; 95% CI, 0.97–1.14 and 1.02; 95% CI, 0.96–1.08, respectively). A novel dynamical model confirmed inherent fertility (probability of ever achieving a pregnancy) was balanced between groups (odds ratio, 1.23; 95% CI 0.78–1.95]). The per-cycle probability of singleton live birth was not different between groups (odds ratio 1.11 [95% CI 0.94–1.3]). In this retrospective cohort study of fresh vs. frozen elective single embryo transfer, there was no statistically significant difference in singleton live birth rate after adjustment using log-linear models and propensity score analysis. The successful application of a novel dynamical model, which incorporates multiple assisted reproductive technology cycles from the same woman as a surrogate for inherent fertility, offers a novel and complementary perspective for assessing interventions using national surveillance data. [ABSTRACT FROM AUTHOR]

To verify the accuracy of an online algorithm using Bayes' theorem for diagnosing ectopic pregnancy (EP) using human chorionic gonadotropin (hCG), ultrasound, and clinical data in a real cohort. A retrospective cohort study. Gynecologic emergency unit in a tertiary teaching hospital. First-trimester pregnant women who attended the gynecologic emergency unit for any reason. Those who had <13 weeks of pregnancy confirmed by a recent positive pregnancy test; a digital image or electronic report of transvaginal ultrasound (TVUS) obtained from hospital database; and a follow-up with a pathology report or a clinical resolution of a confirmed pregnancy were included in the study. Clinical signs and symptoms, the presence of risk factors for EP, the TVUS findings in each consultation, and the hCG levels were independent variables obtained from the electronic medical records. From these data, the pretest probability, based on the clinical presentation and risk factors, and the likelihood ratio for each variable were calculated for their use in the algorithm, yielding a posttest probability. Not applicable. The accuracy of the online algorithm to identify cases of EP using clinical signs and symptoms, the presence of risk factors for EP, the TVUS findings in each consultation, and the hCG levels. The main outcome was EP, confirmed either by pathology report or by the presence of fetal heartbeat or gestational sac outside the uterine cavity. Between January 1, 2009 and December 27, 2016, 2,495 women were analyzed, and the algorithm was applied to 2,185 of them. The incidence of EP was 8.5% (212/2,495); 310 women were excluded because they were submitted to surgery with decision thresholds <95%. The algorithm was applied to 2,185 women. Just one case remained inconclusive after 3 consultations, and it was considered as an error in prediction. The sensitivity, specificity, and accuracy values (95% confidence interval) of the algorithm were 98.9% (96.1%–99.8%), 98.9% (98.3%–99.2%), and 98.9% (98.3%–99.2%), respectively. The accuracy of the Bayesian algorithm to confirm or rule out EP is excellent. Online Nomogram https://docs.google.com/spreadsheets/d/1jStXlMBjbPyDf6_W0deKGKQLZHU5EFAe8rLhNVPuJuY/edit?usp=sharing [ABSTRACT FROM AUTHOR]

Objective: Successful medical management of an ectopic pregnancy is inversely associated with initial hCG level. The purpose of this publication is to assess whether there is a level of hCG above which failure rate substantially increases. Design: A systematic review and summary analysis was performed, including studies reporting methotrexate treatment outcomes as stratified by various hCG ranges. Setting: Academic medical center. Patient(s): Review of published information regarding patients treated with methotrexate. Intervention(s): None. Main Outcome Measure(s): Success and failure rate of medical management. Result(s): Five observational studies, including 503 women, were found that reported successes in using single-dose methotrexate stratified by initial hCG concentration. Failure rates increase with increasing hCG levels. A substantial and statistically significant increase in failure rates is seen when comparing patients who have initial hCG levels of >5,000 mIU/mL with those who have initial levels of <5,000 mIU/mL (odds ratio: 5.45; 95% confidence interval: 3.04, 9.78). The failure rate for women who had an initial concentration between 5,000 and 9,999 mIU/mL was significantly higher than that for those who had initial levels between 2,000 and 4,999 mIU/mL (odds ratio: 3.76; 95% confidence interval: 1.16, 12.33). Conclusion(s): Results support a substantial increase in failure of medical management with single-dose methotrexate when the initial hCG is above 5,000 mIU/mL. Methotrexate should be used with caution in patients with ectopic pregnancy who present with hCG levels above this level. [Copyright &y& Elsevier]

Objective: To compare the cost and complication rate of two alternative strategies for the diagnosis and medical management of ectopic pregnancy when ultrasound is nondiagnostic. Design: A decision tree was constructed to compare [1] dilatation and curettage (D&C) followed by treatment of all ectopic pregnancies with methotrexate versus [2] empiric treatment of all patients with possible ectopic pregnancies with methotrexate without D&C. Setting: University setting. Patient(s): Ten thousand hypothetical women with nonviable pregnancies and a known incidence of ectopic pregnancy were entered into a computer model. Main outcome measure(s): The two approaches were compared with respect to the number of missed ectopic pregnancies, complications, procedures performed, admissions to the hospital, and cost. Result(s): The D&C group had 1% more failed managements of ectopic pregnancies and 13.4% fewer patients with a miscarriage undergo a second treatment for resolution. The D&C group had 13.7% fewer complications including 6.3% fewer hospitalizations. D&C costs $173 to $223 more than empiric use of methotrexate per patient. Conclusion(s): Empirically treating women at risk for ectopic pregnancy with methotrexate does not reduce complications or save money. In the absence of such savings, the desire to make an accurate and definitive diagnosis, allowing objective prognosis on future fertility and risk of repeat ectopic pregnancy, supports the need to distinguish a miscarriage from ectopic pregnancy before treatment with methotrexate. [Copyright &y& Elsevier]