Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss.

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5-18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3-11·4%), two miscarriages is 1·9% (1·8-2·1%), and three or more miscarriages is 0·7% (0·5-0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need to be available. We recommend that miscarriage data are gathered and reported to facilitate comparison of rates among countries, to accelerate research, and to improve patient care and policy development.

Cost-effectiveness of cytogenetic evaluation of products of conception by chorionic villus sampling in recurrent miscarriage.

OBJECTIVE: To compare the cost-effectiveness of performing chorionic villus sampling (CVS) of products of conception (POC) in the evaluation of recurrent miscarriage versus standard evidence-based work-up (EBW) of the couple. MATERIAL AND METHODS: A decision-analytic model was performed in couples with a third miscarriage. Three strategies were considered: (1) the standard EBW of all the patients, comprising parental karyotype, uterine cavity assessment and antiphospholipid antibodies; (2) performing a CVS of POC and a standard karyotype, and if euploid, follow with EBW; and (3) performing a CVS of POC and an arrayCGH and, if normal, follow with EBW. Estimated cost and diagnostic yield of each strategy was analysed. Sensitivity analysis and threshold cost were considered. RESULTS: The expected cost-effectiveness of CVS and karyotype of POC in recurrent miscarriage was: $US769.79 versus $US 1361.8 for the standard EBW of the couple. When stratified by maternal age the results remained cost-effective for this strategy. The arrayCGH strategy has a higher diagnostic yield, but still expensive in our setting to be considered cost-effective. CONCLUSIONS: Chorionic villus sampling and karyotype analysis of products of conception in a third miscarriage proved a more cost-effective strategy than standard EBW of the couple. © 2017 John Wiley & Sons, Ltd.

The Importance of an Evidence-based Workup for Recurrent Pregnancy Loss.

Choosing an evidence-based workup and treatment for recurrent pregnancy loss is imperative to provide best patient care and create a culture that permits rigorous research into potential (not yet evidence-based) tests and therapeutics. As health sciences technologies become more sophisticated, more precise, and less expensive, new tools may be developed that allow better evaluation and treatment of couples with recurrent pregnancy loss. The goal must remain optimizing value and adhering to evidence-based care.

Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss.

OBJECTIVE: To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). DESIGN: Decision analytic model comparing costs and clinical outcomes. SETTING: Academic recurrent pregnancy loss programs. PATIENT(S): Women with unexplained RPL. INTERVENTION(S): IVF/PGS with 24-chromosome screening and expectant management. MAIN OUTCOMES MEASURE(S): Cost per live birth. RESULT(S): The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. CONCLUSION(S): In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management.

Should factor V Leiden mutation and prothrombin gene polymorphism testing be done in women with recurrent miscarriage from North India?

PURPOSE: Role of thrombophilic factor (FV) in the etiology of recurrent miscarriages is not confirmed till date. It has been hypothesized that thrombophilic G1691A factor V Leiden (FVL), if detected well ahead in time among recurrent miscarriages may be a treatable. The role of FVL mutation in the pathogenesis of sporadic and recurrent miscarriages among North Indian women was studied to construct the frequency data in this part of the country. Further, we have evaluated the cost-benefit factor. METHODS: This is a case-control study, women with recurrent miscarriages (n = 1,000) as cases and healthy parous women (n = 500) as controls were enrolled in the study between January 2003 and January 2012. DNA was extracted from peripheral blood and analyzed for the presence of FVL mutation and prothrombin gene polymorphism (G20210A). We have carried out the meta-analysis taking into consideration 20 other world populations. RESULTS: In total, 50 (5.0 %) cases and 12 (2.4 %) controls were heterozygous for the FVL mutation. The incidence of FVL was higher in recurrent miscarriage cases as compared to the control group (OR 2.14; 95 % CI 1.12-4.05). CONCLUSION: Our results revealed the absence of FVL mutation in a homozygous state among patients and controls. Although the heterozygous mutation is almost double in cases as compared to controls, we still suggest that looking at the cost-benefit analysis this test may not be included in the battery of tests performed on recurrent miscarriages among North Indians from this part of the country.

Cost-effectiveness of cytogenetic evaluation of products of conception in the patient with a second pregnancy loss.

OBJECTIVE: To compare the cost of two strategies for managing the patient with recurrent pregnancy loss (RPL). DESIGN: Cost analysis using a decision analytic model was used to compare obtaining an evidence-based workup (EBW) for RPL versus obtaining a karyotype of the products of conception (POC) and proceeding with an EBW only in the setting of euploid POC. SETTING: Outpatient care. PATIENT(S): A simulated cohort of patients experiencing a second pregnancy loss. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Total cost of investigating the cause of RPL after a second pregnancy loss. RESULT(S): For all age categories, obtaining a karyotype of POC was less costly than an evidenced-based RPL evaluation. Monte Caro analysis demonstrated a net economic benefit for the karyotype strategy ($4,498 [±$792] vs. $5,022 [±$1,130]). CONCLUSION(S): Our model suggests an economic advantage for obtaining a karyotype of POC in women with second miscarriage.

Is chromosome testing of the second miscarriage cost saving? A decision analysis of selective versus universal recurrent pregnancy loss evaluation.

OBJECTIVE: To compare the cost of selective recurrent pregnancy loss (RPL) evaluation, which is defined as RPL evaluation if the second miscarriage is euploid, versus universal RPL evaluation, which is defined as RPL evaluation after the second miscarriage. Traditionally, an RPL evaluation is instituted after the third miscarriage. However, recent studies suggest evaluation after the second miscarriage, which dramatically increases health care costs. Alternatively, chromosome testing of the second miscarriage, to determine whether an RPL evaluation is required, has been proposed. DESIGN: Decision-analytic model. SETTING: Academic medical center. PATIENT(S): Couples experiencing a second miscarriage of less than 10 weeks size. INTERVENTION(S): Selective versus universal RPL evaluation after the second miscarriage. MAIN OUTCOME MEASURE(S): Estimated cost for selective versus universal RPL evaluation. RESULT(S): The estimated cost of selective RPL evaluation after the second miscarriage was $3,352, versus $4,507 for universal RPL evaluation, resulting in a cost savings of $1,155. With stratification by maternal age groups, selective RPL evaluation resulted in increased cost savings with advancing maternal age groups. CONCLUSION(S): Selective RPL evaluation, which is based upon chromosome testing of the second miscarriage, is a cost-saving strategy for couples with RPL when compared with universal RPL evaluation. With advancing maternal age groups, the cost savings increased.

Frequency of etiological factors and cost effectiveness of the work up for patients with history of recurrent pregnancy loss.

OBJECTIVE: To assess the frequency of the etiological factors during the evaluation of patients with recurrent abortions. The cost effectiveness of the most frequent positive findings will be assessed. STUDY DESIGN: This is a retrospective study in which 97 patient charts were evaluated and only 90 charts were included in this study. The diagnostic studies for every patient including hysterosalpingogram, endometrial biopsy, cervical cultures for Chlamydia and ureaplasma, and chromosomal karyotyping for the couple were assessed. The cost analysis was based on the CPT coding for each test. RESULTS: The frequency of the tests with highest positive findings were hysterosalpingogram, endometrial biopsy, cervical cultures, and immunologic studies. Chromosomal karyotyping has a low positive yield in evaluation of these patients. CONCLUSION: In evaluating patients with recurrent miscarriages, treating physicians should take into consideration the tests which have a high positive yield as a first step. Chromosomal karyotyping should be evaluated in specific situations.

Resection of uterine septum using gynaecoradiological techniques.

This paper presents further refinements in our technique for the resection of uterine septum. Fourteen patients [infertility (n = 9) and recurrent miscarriages (n = 5)] underwent in-office resection of a uterine septum under fluoroscopic control. The main outcome measure was complete resection of uterine septum. Resections were carried out using either hysteroscopic scissors in combination with a specially designed uterine balloon catheter, or microlaparoscopy scissors in conjunction with a cervical cannula. In all patients the septum was successfully resected without any intra-operative complications. We conclude that ambulatory gynaecoradiological resection of uterine septa is a safe and simple procedure. It avoids utilization of expensive operating room time, general anaesthesia, and some complications associated with hysteroscopic resection, such as fluid retention and electrolyte imbalance.