Higher-order Multiple Gestations Research Articles

Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients.

To compare frequency of perinatal death between pregnant patients who completed the mRNA coronavirus disease 2019 (COVID-19) vaccination series and unvaccinated patients. This retrospective cohort study included 15,865 pregnant patients who delivered 16,132 newborns after 20 weeks of gestation within a large regional health system between January 1, 2021, and December 31, 2021. Patients who received two doses of mRNA vaccine (Pfizer-BioNTech [BNT162b2] or Moderna [mRNA-1273]) were included in the vaccinated group and were compared with unvaccinated patients. Exclusions included partial vaccination, viral-vector vaccine, major congenital anomalies, and higher-order multiple gestation. Our primary outcome was perinatal death, including stillbirth and neonatal death, which was evaluated by logistic regression. Unadjusted odds ratios and adjusted odds ratios (aORs) were reported, controlling for age, body mass index (BMI), diabetes, hypertension, smoking, twin gestation, and insurance status. Propensity score matching was also performed. A total of 15,865 patients were included in the final analysis: 2,069 in the vaccination group and 13,796 in the control group. Only 13.0% of the cohort was included in the vaccination group; however, the vaccination rate increased over the course of the study period as the vaccine became more widely available and accepted. Vaccinated patients were older, with higher rates of people of non-Black racial non-Hispanic ethnic backgrounds, people with private insurance, and those with higher BMIs. Vaccination was associated with a lower incidence of perinatal death (0.5% vaccinated group vs 0.8% unvaccinated group, aOR 0.20 0.05-0.88). Vaccination against COVID-19 was also associated with lower rates of preterm delivery (aOR 0.63, 0.48-0.82), neonates with very low birth weight (aOR 0.35, 0.15-0.84), and neonatal intensive care unit (NICU) admission (aOR 0.66, 0.52-0.85). The association between vaccination and lower rates of perinatal death was no longer significant after propensity score matching. In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. Although the decreased rates of perinatal death did not remain significant after propensity score matching, there was evidence of directional benefit for vaccinated patients.

Factors associated with appropriate administration of magnesium sulfate for neuroprotection prior to early preterm birth

To evaluate factors associated with appropriate administration of magnesium sulfate (MgSO4) for fetal neuroprotection prior to preterm birth (PTB) in a large United States university-based health system. Multicenter retrospective cohort of all PTBs between 23 0/7-31 6/7 weeks’ gestation from 1/1/2019 to 12/31/21. Exclusion criteria included patients with hypertensive disorders of pregnancy (to assure only indication for MgSO4 administration was fetal neuroprotection and not maternal seizure prophylaxis), stillbirths, higher-order multiple gestations, and extramural deliveries. Cases were stratified into two groups based on whether MgSO4 was administered prior to PTB or not. Maternal characteristics were compared between the two groups using Chi-squared or Mann-Whitney U test with statistical significance set at P < 0.05. A subgroup analysis evaluating reasons for lack of administration in those who did not receive MgSO4 prior to delivery was also performed. Of the 527 patients included, 438 (83.1%) received MgSO4 prior to delivery. Baseline characteristics and delivery outcomes compared between the two groups are displayed in Table 1. Patients who did not receive MgSO4 prior to delivery were more commonly admitted for fetal status abnormalities and non-obstetric complaints, and had a significant shorter median time interval from arrival to delivery (1.5 hours vs. 59.0 hours, P = < 0.001) (Table 1). Lack of adherence to health system protocol for MgSO4 administration occurred in 16.9% (15/89, 2.8% of overall study cohort) of patients who did not receive MgSO4 prior to delivery (Table 2). The overall adherence to a protocol of MgSO4 administration for fetal neuroprotection prior to early PTB was high. Admission for fetal status abnormalities and non-obstetric complaints were more common among patients who did not receive MgSO4 prior to delivery, with most patients who did not receive MgSO4 either arrived < 2 hours from delivery or had an acute change in maternal/fetal status requiring immediate delivery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Making and selecting the best embryo in the laboratory

Over the past 4 decades our ability to maintain a viable human embryo invitro has improved dramatically, leading to higher implantation rates. This has led to a notable shift to single blastocyst transfer and the ensuing elimination of high order multiple gestations. Future improvements to embryo culture systems will not only come from new improved innovative media formulations (such as the inclusion of antioxidants), but plausibly by moving away from static culture to more dynamic perfusion-based systems now made a reality owing to the breakthroughs in three-dimensional printing technology and micro fabrication. Such an approach has already made it feasible to create high resolution devices for intracytoplasmic sperm injection, culture, and cryopreservation, paving the way not only for improvements in outcomes but also automation of assisted reproductive technology. Although improvements in culture systems can lead to further increases in pregnancy outcomes, the ability to quantitate biomarkers of embryo health and viability will reduce time to pregnancy and decrease pregnancy loss. Currently artificial intelligence is being used to assess embryo development through image analysis, but we predict its power will be realized through the creation of selection algorithms based on the integration of information related to metabolic functions, cell-free DNA, and morphokinetics, thereby using vast amounts of different data types obtained for each embryo to predict outcomes. All of this will not only make assisted reproductive technology more effective, but it will also make it more cost effective, thereby increasing patient access to infertility treatment worldwide.

Spontaneously Conceived Quadruplet with Three Viable Babies &amp; A Papyraceous Fetus: A Case Report

Background: High order multiple gestations are an uncommon occurrence. The incidence of multiple gestation continues to decrease as the number of fetuses increase as calculated using Hellin’s rule: incidence = 1:80n-1 births, where n is the number of fetuses. Thus, the expected incidence of quadruplets is estimated at 1 in 512,000 births. All these have changed with the advent of reproductive technology. However, the occurrence of quadruplets as a natural process has remained rare globally. Objective: To report a case of a successful spontaneously conceived quadruplet with the death of one of the fetuses and delivery of 3 live fetuses and a twin papyraceous fetus at the 36th week of gestation. Methods: We report a case of a 28-year-old para-2 woman who had a spontaneous conception resulting in a quadruplet. She had an ultrasound diagnosis of death of one of the fetuses at 25 weeks of gestation. She was admitted twice in the course of the pregnancy and subsequently delivered at the 35th week of gestation. Results: A successful caesarean delivery of 2 fem ales and 1 male with a male papyraceous fetus.

Restorative reproductive medicine for infertility in two family medicine clinics in New England, an observational study

BackgroundRestorative reproductive medicine (RRM) seeks to identify and correct underlying causes and factors contributing to infertility and reproductive dysfunction. Many components of RRM are highly suitable for primary care practice. We studied the outcomes amongst couples who received restorative reproductive medicine treatment for infertility in a primary care setting.MethodsTwo family physicians in Massachusetts trained in a systematic approach to RRM (natural procreative technology, or NaProTechnology) treated couples with infertility. We retrospectively reviewed the characteristics, diagnoses, treatments, and outcomes for all couples treated during the years 1989 to 2014. We compared pregnancy and live birth by clinical characteristics using Kaplan-Meier analysis. We employed the Fleming-Harrington weighted Renyi test or the logrank test to compare the cumulative proportion with pregnancy or with live birth.ResultsAmong 370 couples beginning treatment for infertility, the mean age was 34.8 years, the mean prior time trying to conceive was 2.7 years, and 27% had a prior live birth. The mean number of diagnoses per couple was 4.9. Treatment components included fertility tracking with the Creighton Model FertilityCare System (80%); medications to enhance cervical mucus production (81%), to stimulate ovulation (62%), or to support the luteal phase (75%); and referral to female laparoscopy by a surgeon specializing in endometriosis (46%). The cumulative live birth rate at 2 years was 29% overall; this was significantly higher for women under age 35 (34%), and for women with body mass index < 25 (40%). There were 2 sets of twins and no higher-order multiple gestations. Of the 63 births with data available, 58 (92%) occurred at term.ConclusionsFamily physicians can provide a RRM approach for infertility to identify underlying causes and promote healthy term live births. Younger women and women with body mass index < 25 are more likely to have a live birth.

895 Maternal and neonatal outcomes associated with preimplantation genetic testing in IVF twin pregnancies

The impact of preimplantation genetic testing (PGT) on pregnancy outcomes with twin gestations is not well known. The objective of this study was to determine whether PGT is associated with adverse maternal and neonatal outcomes in twin pregnancies conceived using vitro fertilization (IVF). Retrospective cohort of multiple gestations conceived via IVF and delivered within a university health system between January 2014 and August 2019. Higher-order multiple gestations (triplet or higher) and cases with missing outcome data were excluded. Adverse maternal outcomes, i.e. hypertensive disorders of pregnancy, abnormal placentation, preterm birth, and adverse neonatal outcomes were compared between twin pregnancies conceived after transfer of one or two PGT screened euploid embryos versus untested embryos. Statistical analysis included use of Chi-square and Wilcoxon rank sum tests, as well as multivariate backwards-stepwise logistic regression, with significance defined as P value < 0.05. Data was presented as adjusted Odds Ratios (OR) with 95% confidence intervals (95% CI). Of 145 twin pregnancies, 43 (29.7%) were conceived following euploid embryo transfer and 102 (70.3%) were conceived following untested embryo transfer. Women who underwent PGT had a significantly lower mean body mass index compared to those that did not (Table 1). Use of donor egg and IVF cycle type (fresh vs. frozen) also differed between the two groups (Table 1). After adjusting for potential confounders, there was no significant difference between the two groups with respect to adverse maternal outcomes or in adverse neonatal outcomes (Table 2). Our data suggest no increase in adverse maternal or neonatal outcomes associated with PGT in twin IVF pregnancies. While our findings are reassuring, future studies utilizing larger cohorts of twin pregnancies are needed.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction.

Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade > I, retinopathy of prematurity Stage > II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n=18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

The impact of cesarean section on neonatal outcomes at a university-based tertiary hospital in Jordan

BackgroundOver the past two decades, there has been a steady rise in the rate of Cesarean section delivery globally. As a result, short-term and long-term maternal and neonatal complications are rising. The objective of this study is to determine the rate and indications for Cesarean section at King Abdullah University Hospital (KAUH) in Jordan and to assess the resulting neonatal outcomes.MethodsA retrospective chart review was conducted for all women and neonates delivered by Cesarean section during the period January 2016 to July 2017 at KAUH tertiary academic center. Collected data include demographic characteristics, indication for delivery, and neonatal outcomes such as NICU admission, respiratory complications, sepsis, mortality, and length of hospitalization.ResultsTwo thousand five hundred ninety-five Cesarean section deliveries were performed over 18 months representing a rate of 50.5% of all deliveries. Sixty percent were scheduled procedures. Seventy-two percent were performed at full term gestation. The most common indication was previously scarred uterus (42.8%) followed by fetal distress (15.5%). The rate of admission to the neonatal ICU was 30% (800/2595). After multilogistic conditional regression analysis, the factors associated with increased risk of neonatal ICU admission were found to include grandmultiparity (Adjusted OR 1.46), gestational diabetes (Adjusted OR 1.92), maternal employment (Adjusted OR 1.84), prolonged rupture of membranes (Adjusted OR 5), fetal distress (Adjusted OR 1.84), prematurity (Adjusted OR 43.78), low birth weight (Adjusted OR 42), high order multiple gestation (Adjusted OR 9.58) and low 5-min APGAR score (Adjusted OR 10). Among the babies electively delivered at early term (37–38.6 weeks), 16% were admitted to the NICU for a median length of stay of 4 days (IQR 2, 8). The most common diagnoses for admitted term neonates were transient tachypnea of newborns and respiratory distress syndrome.ConclusionsCS deliveries account for more than half the number of deliveries at our institution and almost one third of the delivered babies are admitted to the NICU. Together with the resulting maternal and neonatal consequences, this carries a major burden on the newborns, health care facilities, and involved families. Local strategies and policies should be established and implemented to improve the outcome of births.

Prevalence of Gestational Diabetes in Triplet Pregnancies: A Retrospective Cohort Study and Meta-Analysis.

Background: Over the last decades, there has been a substantial increase in the incidence of higher-order multiple gestations. Twin pregnancies are associated with an increased risk of gestational diabetes mellitus (GDM). The literature on GDM rates in triplet pregnancies is scarce. Methods: A retrospective cohort study was performed to assess the prevalence of GDM in women with a triplet pregnancy. GDM was defined through an abnormal oral glucose tolerance test (OGTT). A meta-analysis of GDM prevalence was also carried out. Results: A cohort of 60 women was included in the analysis. Of these, 19 (31.7%) were diagnosed with GDM. There were no differences in pregnancy outcomes between women with and without GDM. In the meta-analysis of 12 studies, which used a sound GDM definition, an estimated pooled prevalence of 12.4% (95% confidence interval: 6.9–19.1%) was found. In a leave-one-out sensitivity analysis, the estimated GDM prevalence ranged from 10.7% to 14.1%. Conclusion: The rate of GDM seems increased in women with triplets compared to singleton pregnancies. However, GDM did not impact short-term pregnancy outcomes.

Mature Follicle Count and Multiple Gestation Risk Based on Patient Age in Intrauterine Insemination Cycles With Ovarian Stimulation.

To estimate the risk of a multiple gestation pregnancy in ovarian stimulation intrauterine insemination (IUI) cycles when stratified by patient age and mature follicle number. We conducted a retrospective cohort study at a single private practice fertility center of IUI cycles performed from 2004 to 2017. Intervention(s) were ovarian stimulation and IUI if postwash total motile sperm count was more than 8 million. Mature follicles were defined as 14 mm or more as measured on the day of ovulation trigger. Main outcomes and measures were rates of clinical pregnancy and multiple gestation. We identified 24,649 women who underwent a total of 50,473 IUI cycles. Increasing the number of mature follicles from one to five at the time of IUI in women younger than age 38 years increased the clinical pregnancy rate from 14.6% to 21.9% (adjusted odds ratio [aOR] 1.6, 95% CI 1.4-1.9), almost entirely from a marked increase in multiple gestations per cycle from 0.6% to 6.5% (aOR 9.9, 95% CI 6.9-14.2). There was little increase in singleton pregnancies per IUI (14.1-16.4%) regardless of mature follicle number. The per-pregnancy twin and higher-order multiple gestation risk significantly increased (3.9-23.3%, P<.01 and 0.2-10.6%, P<.01, respectively) when comparing one with five mature follicles present at the time of IUI (P<.01). In women younger than age 38 years with more than three follicles present, more than one quarter of all pregnancies were multiples. Similar findings occurred in women aged 38-40 years. In women older than age 40 years, up to four follicles tripled the odds of pregnancy (aOR 3.1, 95% CI 2.1-4.5) while maintaining a less than 12% risk of multiple gestation per pregnancy and a 1.0% absolute risk of multiples. Caution should be used in proceeding with IUI after ovarian stimulation when there are more than two mature follicles in women younger than age 40 years owing to the substantially increased risk of multiple gestation without an improved chance of singleton clinical pregnancy.

Predictors of Gestational Diabetes Among Women Living in Food Deserts [30D

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with many adverse maternal and fetal outcomes. The aim of this study is to identify the relationship between GDM and access to affordable grocery stores. METHODS: This is a retrospective review of patients delivering at a single institution. Food insecurity was determined using patient address overlaid with USDA Food Access Research Atlas. Patients living &gt;0.5 miles from a supermarket were identified as living in a food desert (FD). GDM clinical data was compared to FD data using chi square, regression analyses. RESULTS: Of 744 patients meeting inclusion criteria, 74 (9.94%) were diagnosed with GDM during their current pregnancy with 2.55% having a previous history of GDM. 517 patients lived in FD and were more likely to be multiparous and of minority race. 60.8% (45/74) of patients diagnosed with GDM during the current pregnancy lived in a FD. The frequency of GDM in women living in FDs was lower than those in Food Secure (FS) tracts (0.09% vs 1.2%, P=.1). Women living in FDs with GDM experienced greater rates of chronic hypertension than those in FS areas (15.2% vs 10.3%, P=.002). Higher order multiple gestation, advanced maternal age, preeclampsia with severe features, and history of GDM were significant predictors for GDM in women living in FD (P&lt;.05). CONCLUSION: Women living in food deserts are not at an increased risk for GDM but are for having chronic hypertension if they have GDM compared to those living in FS.

Families with children resulting from ART: psychosocial and financial implications.

STUDY QUESTIONWhat are the psychosocial and financial issues experienced among families with children 2–12 years of age conceived by ART?SUMMARY ANSWEROur results suggest that families with children, 2–12 years of age, conceived via ART are doing well, although impacts were identified on parents of twins and higher-order multiples.WHAT IS KNOWN ALREADYMultiple births have been associated with higher morbidity and mortality of children, as well as financial costs to families and society.STUDY DESIGN, SIZE, DURATIONThis study was an assessment of familial response to birth of singletons, twins and higher order multiples at child’s ages of 2–12.PARTICIPANTS/MATERIALS, SETTING, METHODSSemi-structured interviews and surveys were conducted with mothers (n = 348) and fathers (n = 338) of singletons, twins and higher-order multiple gestations who received fertility services.MAIN RESULTS AND THE ROLE OF CHANCENo significant differences were observed between the groups in domains of primary caregiving or parental separation/divorce. Impacts were identified on parent’s ability to maintain employment. The revised 15-item scores of the Impact on Family Scale were significantly lower, reflecting more negative impacts, among families with twins (beta = −2.6, 95% confidence interval (CI), −4.7, −0.5, P = 0.014) and multiples (beta = −7.4, 95% CI, −10.4, −4.5, P < 0.001) than among families with singletons. Similarly, the Parenting Stress Index total scores were significantly lower among families with twins and multiples, indicating greater levels of stress, when compared to those with singletons. In addition, the Beck Depression Inventory total score were significantly higher for twins and multiples, and the Child Behaviour Checklist for ages 1.5–5 total problem score was significantly higher for twins when compared to singletons.LIMITATIONS, REASONS FOR CAUTIONThe study was limited to families who received fertility treatment and constitutes a population that was well educated and had higher incomes. Additionally, interview data was self-reported.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) U10 HD39005 (to M.P.D.), U10 HD077680 (to K.R.H.), U10 HD077844 (to A.Z.), U10 HD077841 (to M.C.), U10 HD38992 (to R.S.L.), U10 HD27049 (to C.C.), U10 HD055925 (to H.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or NIH.Dr Virginia Miller—no conflicts; Dr Michael P. Diamond—NIH Funding, AbbVie, Bayer and ObsEva Funding; Board of Directors and Stockholder for Advanced Reproductive Care; Dr Karl R. Hansen—Yale University/Reproductive Medicine Network/NICHD, Roche Diagnostics and Ferring International Pharmascience Center US funding; Dr Anne Steiner—NIH Funding; Dr Marcelle I. Cedars—no conflicts; Dr Richard Legro—consultant for Ogeda, Millendo, Kindex and Bayer; Ferring and Astra Zeneca funding; Dr Stephen A. Krawetz—no conflicts; Dr Christos Coutifaris—NIH Funding; Dr Hao Huang—no conflicts; Dr Nanette Santoro—no conflicts; Dr Heping Zhang—NIH Funding.TRIAL REGISTRATION NUMBERN/A

Outcomes of singleton versus twin pregnancies in the fifth and sixth decades

BackgroundPregnancies in the fifth and sixth decades of life have been increasing, but current data are limited regarding the outcomes of twin compared with singleton pregnancies in this age group and to twin pregnancies at younger age. ObjectiveTo compare obstetrical and neonatal outcomes of IVF conceived pregnancies, in twin gestations of women who were ≥45 years old at delivery to singletons at similar age and twin gestations at the age of <35 years, and to assess if the complications are mainly influenced by the very advanced maternal age or by the multifetal pregnancy. Study DesignA retrospective cohort study from a single tertiary medical center of women aged ≥45 at delivery between March 2011 and January 2018 and women aged <35 at delivery with twin pregnancies that conceived by IVF. Exclusion criteria were spontaneous pregnancies or pregnancies after ovulation induction, monochorionic twin pregnancies, higher order multiple gestations, or women that underwent fetal reduction. Pregnancy, delivery, postpartum and neonatal outcomes were compared between singleton and twin pregnancies. Multivariate logistic regression was used to evaluate the association between twin pregnancies and adverse outcomes. ResultsOut of 67,355 deliveries, 612 were of women ≥45 years old, of whom 492 women conceived via IVF (395 singleton and 97 twin pregnancies). Of those, 60 women were ≥50 years old, 49 of them carried singleton and 11 carried twin pregnancies. Baseline characteristics were similar between groups. Women at the fifth and sixth decades with twins had significantly higher rates of preeclampsia (32.0% vs. 10.9%, p < 0.001), gestational diabetes mellitus (35.4% vs. 23.8%, p = 0.020), preterm deliveries <32 weeks of gestation (8.2% vs. 1.3%, p = 0.001), and fetal growth restriction (18.6% vs. 7.6%, p = 0.001) compared with singleton pregnancies at similar maternal age. After multivariate analysis adjusting for confounders, the odds ratio for the composite of preeclampsia, gestational hypertension, intrauterine fetal growth restriction, and placental abruption was 3.19 for twin compared with singleton pregnancies and 1.73 for gestational diabetes mellitus. Pregnancy complications among older women with twins were also significantly higher when compared with younger women with twins (<35 years old). Women in the fifth and sixth decades with twins had higher rates of cesarean deliveries (91.8% vs. 56.4%, p<0.001), gestational hypertension, preeclampsia, and gestational diabetes mellitus (10.3% vs. 4.2%., p=0.016; 32.0% vs. 6.2%, p<0.001; 35.1% vs. 8.1%, p<0.001, respectively) than the younger group carrying twins. ConclusionsTwin pregnancies in the fifth and sixth decades carry significantly higher complications rate compared with singleton pregnancies at the same age and twin pregnancies at younger age.

Multi-fetal pregnancy reduction (MFPR) to twins or singleton - medical justification and ethical slippery slope.

Multi-fetal pregnancy reduction (MFPR) is an ethically acceptable procedure aimed to increase survival and well-being of the remaining fetuses from high-order multiple gestations. In most cases we offer the procedure to triplets or quadruplets and opt to preserve twins; lately, the option to maintain a single fetus was suggested. We examined the outcomes of 140 pregnancies that underwent MFPR in our center and were followed to delivery - 105 were reduced to twins and 35 to singletons. The rate of procedure-related pregnancy loss was identical (2.9%). Leaving only one fetus was associated with a higher gestational age at delivery (35.4±2.4 weeks vs. 37.7±2.1 weeks, P<0.0001), with heavier neonates (2222 g vs. 3017 g, P<0.0001) and with a reduction in the cesarean section (CS) rate (76% in twins vs. 51.4% in singletons, P=0.02). Six pregnancies reduced to twins (5.8%) ended before 32 weeks as compared to one pregnancy reduced to a singleton. We conclude that reduction of triplets to singletons is medically and ethically acceptable, after thorough counseling of patients. However, considering the pregnancy loss risk of MFPR and the relatively good outcome of twin gestations, reduction of twins to singletons is ethically acceptable only in extraordinary maternal or fetal conditions.

Economic implications of the Society for Assisted Reproductive Technology embryo transfer guidelines: healthcare dollars saved by reducing iatrogenic triplets

To estimate the national cost savings resulting from reductions in higher-order multiple (HOM) live births (defined as three or more fetuses), following the initial publication of the Society for Assisted Reproductive Technology (SART) guidelines on ET in1998. Descriptive use and cost analysis. Not applicable. Not applicable. Not applicable. Estimates of the total number of HOM deliveries prevented (from 1998-2012) following the publication of SART guidelines; the associated healthcare savings (2014 US dollars). A singleton live birth was estimated to cost $17,100-$24,200. A twin live birth was estimated at $66,000-$117,500. A triplet live birth was estimated at $190,800-$456,300. The percentage of HOM gestations among all ART pregnancies decreased from 11.4% in 1997 to 2.0% in 2012, with the sharpest year-over-year decline of 20.3% occurring in the year following the publication of the guidelines. The number of prevented HOM deliveries from 1998 through 2012 was estimated to be between 13,500 and 16,300, corresponding to cost savings of $6.02B (billion) (range, $2.35B-$7.03B, 2014 US dollars). Iatrogenic HOM gestations represent a substantial economic burden to our healthcare system. The introduction of guidelines for ET in 1998 coincided with a dramatic decrease in the HOM rate in subsequent years and an associated cumulative cost savings of more than $6B. Further reductions in HOM gestations could save up to an additional $2B annually.

In-vitro fertilization and spontaneous pregnancies: matching outcomes in Douala, Cameroon.

BackgroundCouples are considered infertile if they do not conceive over a 12-month period of unprotected intercourse. Studies have shown that female causes accounted for between 25 to 37 percent of infertility worldwide (with larger proportions in sub-Saharan Africa and Southeast Asia) and male causes accounted for between 8 to 22 percent. Both male and female causes accounted for between 21 to 38 percent. Although the majority of ART children are normal, there are concerns about the increased risk for adverse pregnancy outcomes. More than 30 % of ART pregnancies are twins or higher-order multiple gestations (triplets or greater) and more than one half of all ART neonates are the products of multifetal gestations, with an attendant increase in prematurity complications. The aim of this study was to evaiuate the outcome of pregnancies conceived by In-vitro fertilisation compared to those conceived naturally in two hospitals in Douala, Cameroon.MethodsThis was a prospective study carried out from October 1, 2011 to September 30, 2012. Participants were recruited from two hospitals: the Douala General Hospital (DGH) and the Clinique de l’ Aéroport (CDA), also in Douala. A total of 102 women were recruited for study: 51 who conceived by IVF (cases) and 51 who conceived naturally (controls). Of the 102 women, 52.9 % were between 31 – 39 years of age, while 21.6 % were above 40.ResultsParticipants who conceived through IVF-ET were 4.1 times more likely to undergo cesarean delivery than those who conceived naturally [OR 4.10, 95 % CI 1.78–9.42]. Similarly, a higher percentage of patients in the IVF group than those in the control group have never given birth (33.3 % vs 2.0 %) (P < 0.0001). The percentage of multiple pregnancies was 7.5 times higher in the IVF group than in the control group (14.7 % vs.1.96 %) (P = 0.000).The leading indication for cesarean delivery was advanced maternal age (27.3 %) followed by IVF or precious pregnancy (18.2 %).ConclusionsCesarean delivery was more frequent amongst the IVF group than in the control group. The leading indications for cesarean delivery were advanced maternal age and IVF or precious pregnancy.The long-term neonatal outcomes of IVF babies beyond 5-min Apgar scores should be studied in Cameroon and follow-up beyond 1 year encouraged.

Higher-order Multiples

Higher-order multiple gestations have increased since the advent of advanced reproductive technologies. These pregnancies present unique risks to both mothers and fetuses. It is imperative that early diagnosis of chronicity be determined and that proper counseling is performed, so patients understand the risks, evaluation, and management needed.

Multifetal Pregnancy Reduction.

Multiple gestations of triplets or more have a significant increase in perinatal morbidity and mortality compared with twins. On average, triplet gestations deliver at approximately 33.5 weeks. Approximately 25% deliver at <32 weeks and 10% deliver <28 weeks. Maternal complications are also significantly increased. Multifetal pregnancy reduction involves the ultrasonically guided injection of KCl into the fetal thorax to induce asystole. It is performed to reduce the potential for early preterm delivery associated with higher-order multiple gestations. Multifetal pregnancy reduction to twins increases gestational age at delivery by 4 weeks and significantly improves maternal and fetal outcomes.

AB076. Standardization and individualization in controlled ovarian stimulation

Due to the complexity of controlled ovarian stimulation (COS), in its decision-making process, there are a number of factors that should be taken into consideration, like the choices of gonadotropins (Gn) and gonadotropin releasing hormone (GnRH) analogues, COS and luteal phase support protocols, et al. Based on experience from over 30 years of practice, physicians have come to an agreement that more oocytes resulted from an aggressive COS strategy is not always better, while we should do a comprehensive evaluation about the trade-off between maximal accumulative live birth rate and the medical and monetary burden, including the risk of ovarian hyperstimulation syndrome (OHSS) and high-order multiple gestations. In order to individualize COS treatment, the key is to standardize evaluation and categorization of the patients undergoing COS treatment. All the patients could be generally divided into four categories: normal responders, slow responders, hyper responders and poor responders. Most young patients undergoing COS treatment with undiminished ovarian reserve should be categorized as normal responders. For these patients, large-scale meta-analysis suggests that the optimal daily recombinant follicular stimulating hormone (recFSH) stimulation dose is 150-225 IU/day, and patient-tailored adjustment should done based on individual patients characteristics including basal FSH, Anti-Müllerian hormone (AMH), body mass index and age et al. The definition of the term ‘hyper response’ refers to the retrieval of >15 oocytes and a rapid rise in estradiol levels. Previous history of OHSS and makers of ovarian reserve, in particular AMH and antral follicle counting (AFC) strongly suggest the possibility of showing a high response to a standard COS protocol. The prevalence of hyper response in all IVF cycles is estimated to be 3-6%. Patients with polycystic ovary syndrome (PCOS) have increased Gn sensitivities and present a higher risk of developing OHSS. The narrow margin between an inadequate Gn dose and excessive stimulation (OHSS) is a challenging situation. An inadequate Gn dose is not capable to stimulate multiple follicles development, resulting in cycle cancellation, while excessive ovarian stimulation in these patients commonly leading to a certain degree of OHSS. A low starting dose of Gn, 37.5 IU, is recommended by the consensus on PCOS infertility treatment endorsed by both the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine. Poor ovarian response indicates a reduction in follicular response, at least two of the following features must be present: (I) advanced maternal age (≥40 years) or any other risk factor for poor ovarian response; (II) a previous poor ovarian response (≤3 oocytes with a conventional stimulation protocol); (III) an abnormal ovarian reserve test (i.e., AFC <5-7 follicles or AMH <0.5-1.1 ng/mL). For these poor responders, the supplementation of recLH is beneficial. Significantly more oocytes and better clinical pregnancy rate could be achieved in women treated with recFSH plus recLH vs. recFSH alone. In our reproductive medical center, a comprehensive protocol is employed to better the outcomes of the poor responders, including DHEA pretreatment, oral contraceptive pretreatment, high-dose recFSH priming, supplementation of recLH et al. Besides these categories of patients with different sensitivity to ovarian stimulation, slow responders are featured by no follicles larger than 10 mm and low estradiol level (E2 <180 pg/mL) on the 6th day of stimulation. The velocity of their follicle development is also reduced (<2 mm for three consecutive days). According to our practice, adding recombinant luteinizing hormone might be beneficial.

Current practices in the prediction and prevention of preterm birth in patients with higher-order multiple gestations

We sought to determine the interventions utilized by maternal-fetal medicine specialists in the prediction and prevention of preterm labor in higher-order multiple (HOM) gestations. Online questionnaires and email surveys were sent to all the maternal-fetal medicine specialists in Canada (n=122). Questionnaire items included interventions physicians routinely recommended for HOM gestations including: (1) bed rest; (2) cervical length measurement on transvaginal ultrasound; (3) corticosteroids use; (4) cerclage; and (5) tocolytic therapy. Response rate was 66% (81/122), with 68% of respondents in practice for >10 years. Of physicians, 91% did not routinely recommend bed rest (95% confidence interval [CI], 84.7-97.2). In all, 82% (95% CI, 73.63-90.4%) recommended routine cervical length assessment with 32.3% (95% CI, 20.7-43.2) and 37.1% (95% CI, 25.3-48.6) of this group suggesting assessment at 16-18 and 19-21 weeks, respectively. Frequency of assessment varied from biweekly (53.3%; 95% CI, 40.9-65.0), to monthly (23.3%; 95% CI, 12.8-33.1), to a single measurement repeated only if abnormal (12.5%; 95% CI, 4.5-20.8). In all, 28% (95% CI, 18.2-37.8) recommended routine administration of corticosteroids for lung maturation. Timing of administration varied, with 24% initiating steroids between 24-26 weeks, 59% between 27-28 weeks, and 17% after 28 weeks. None reported routine cerclage placement. However, 71% (95% CI, 61.1-80.8) would perform cerclage based on history or ultrasound. Of respondents, 81% (95% CI, 72.4-89.5) would consider using tocolytic agents for threatened preterm labor including calcium channel blockers (94%), nonsteroidal antiinflammatory drugs (5%), and nitroglycerin transdermal patch (24%). The variable practice guidelines and paucity of data for management of HOM pregnancy places the onus on individual practitioners to develop their own management schemes. This results in heterogeneous management, which is based on conflicting international guidelines, studies, expert opinion, or past experience.