Quadruplet pregnancy outcome with and without fetal reduction: Danish national cohort study (2008-2018) and comparison with dichorionic twins.

OBJECTIVES: To perform a nationwide study of quadrichorionic quadriamniotic (QCQA) quadruplet pregnancies and to compare the pregnancy outcome in those undergoing fetal reduction with non-reduced quadruplets and dichorionic diamniotic (DCDA) twin pregnancies from the same time period. METHODS: This was a retrospective Danish national register-based study performed using data from the national Danish Fetal Medicine Database, which included all QCQA quadruplets and all non-reduced DCDA twin pregnancies with an estimated due date between 2008 and 2018. The primary outcome measure was a composite of adverse pregnancy outcomes, including pregnancy loss or intrauterine death of one or more fetuses. Secondary outcomes included gestational age at delivery, the number of liveborn children, preterm delivery before 28, 32 and 37 gestational weeks and birth weight. Data on pregnancy complications and baseline characteristics were also recorded. Outcomes were compared between reduced and non-reduced quadruplet pregnancies, and between DCDA pregnancies and quadruplet pregnancies reduced to twins. A systematic literature search was performed to describe and compare previous results with our findings. RESULTS: Included in the study were 33 QCQA quadruplet pregnancies, including three (9.1%) non-reduced pregnancies, 28 (84.8%) that were reduced to twin pregnancy and fewer than three (6.1%) that were reduced to singleton pregnancy, as well as 9563 DCDA twin pregnancies. Overall, the rate of adverse pregnancy outcome was highest in non-reduced quadruplets (66.7%); it was 50% in quadruplets reduced to singletons and 10.7% in quadruplets reduced to twins. The proportion of liveborn infants overall was 91.1% of the total number expected to be liveborn in quadruplet pregnancies reduced to twins. This was statistically significantly different from 97.6% in non-reduced dichorionic twins (P = 0.004), and considerably higher than 58.3% in non-reduced quadruplets. The rates of preterm delivery < 28, < 32 and < 37 weeks were decreased in quadruplets reduced to twins compared with those in non-reduced quadruplet pregnancies. Quadruplets reduced to twins did not achieve equivalent pregnancy outcomes to those of DCDA twins. CONCLUSION: This national study of QCQA quadruplets has shown that multifetal pregnancy reduction improves pregnancy outcome, including a decreased rate of preterm delivery and higher proportion of liveborn children. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Delayed interval delivery in a quadruplet pregnancy: a case report and literature review.

BACKGROUND: As the rate of multiple pregnancies increases, delayed interval delivery (DID) is increasingly being implemented to improve perinatal outcomes. But there are no international guidelines for DID in multiple pregnancies. We report a case of DID in a quadruplet pregnancy and review the relevant literature to summarize the management of DID in multiple pregnancies. CASE PRESENTATION: A 22-year-old woman, 22 2/7 weeks' gestation, with quadruplets, was admitted to the hospital for a first cervical cerclage due to cervical dilation. Twenty-five days later, it was found that the cervix was dilated again, so after removing the cervical cerclage, the first quadruplet was delivered vaginally (25 6/7 weeks), and a second cervical cerclage was performed. Four days later, due to re-dilation of the cervix, after removal of the cervical cerclage, the second quadruplet was delivered vaginally (26 3/7 weeks), followed by a third cervical cerclage. Six days later, the pregnancy was terminated by cesarean section due to fetal distress, and the third and fourth quadruplets were delivered (27 2/7 weeks). The patient had no postoperative complications, and all four infants were treated in the neonatal intensive care unit and discharged successfully. CONCLUSION: This case emphasizes that comprehensive management of delayed interval delivery can improve perinatal outcomes in multiple pregnancies, including anti-infection, tocolytic therapy, practice to promote fetal lung, and cervical cerclage.

Quadruplet Pregnancy with Complete Mole and Three Viable Fetuses.

Background: The coexistence of a hydatidiform mole and a fetus can occur in a multiple pregnancy, being less frequent in triplets and quadruplets because of their infrequency. With assisted reproduction, multiple pregnancies are becoming more frequent, and we can expect more frequent coexistence with a molar pregnancy. Case report: This G3, P1 30-year-old mother, after assisted conception, was diagnosed with a quadruplet pregnancy, one of which was a molar conceptus. Due to the potential for malignancy, the pregnancy was electively terminated. Conclusion: Despite the difficulty in conceiving, elective termination of a multiple pregnancy associated with a molar pregnancy may be the most judicious course of action to protect the mother's life.

Heterotopic Quadruplet Pregnancy. Literature Review and Case Report.

Heterotopic pregnancy is the condition where both intrauterine and ectopic pregnancy are present. It rarely occurs after natural conception, but is more common with assisted reproductive techniques, when more than one embryo is transferred. Quadruplet heterotopic pregnancy is exceedingly rare. METHODS: A literature review was conducted aiming to highlight the diagnosis difficulties and the management options in heterotopic quadruplet pregnancies. RESULTS: Nine relevant studies were identified by researching PubMed up to 2021 for "heterotopic quadruplet pregnancy", "quadruplet intrauterine and ectopic pregnancy", "synchronous intrauterine and ectopic pregnancy". CONCLUSIONS: In this paper, we present a case of heterotopic quadruplet pregnancy and address the difficulty in diagnosing this condition and make formal recommendations.

Analysis of 122 triplet and one quadruplet pregnancies after single embryo transfer in Japan.

RESEARCH QUESTION: What is the prevalence of triplet and quadruplet pregnancies after single embryo transfer (SET) in Japan. DESIGN: A retrospective observational study was conducted on 274,605 pregnancies after 937,848 SET cycles in registered assisted reproductive technology (ART) data from the Japanese ART national registry database between 2007 and 2014. A questionnaire survey of ART centres was also conducted. Data on pregnancies with embryo division into three or more after SET were analysed. RESULTS: According to the Japanese ART national registry database, SET resulted in 109 triplet pregnancies (0.04% of pregnancies), and the questionnaire reports from 31 centres revealed 33 triplet and one quadruplet pregnancies. After exclusion of 20 duplicated cases, 122 triplet and one quadruplet pregnancies included 46 monochorionic (one gestational sac [37.4%]), 18 dichorionic (two gestational sacs [14.6%]) and 59 trichorionic pregnancies (three gestational sacs [48.0%]). Compared with singleton pregnancies, patients with monozygotic triplet or quadruplet pregnancies were less frequently diagnosed with unexplained infertility (P = 0.004), more often received gonadotrophin injections for ovarian stimulation in 39 cases with information available (P = 0.021) and underwent more blastocyst transfers and assisted hatching (P = 0.002 and P < 0.001, respectively). The proportion of live birth, defined as at least one baby born, excluding induced abortion, was 64.6% (73/116 pregnancies) of monozygotic triplet or quadruplet pregnancies. CONCLUSIONS: Combined Japanese ART national registry and survey data revealed 122 triplet and one quadruplet pregnancies, the majority after cryopreserved embryo transfer. Most were conceived after blastocyst transfer and often after assisted hatching, which are potential risk factors for zygotic splitting.

Single center experience in selective feticide in high-order multiple pregnancy: clinical and ethical issues.

OBJECTIVE: This paper describes the 20-year experience with selective feticide (SF) of high-order multiple quadruplet and higher pregnancies in a single center. METHODS: The paper describes protocols, procedures, management, outcomes, and ethical issues. RESULTS: SF was performed in 49 pregnancies with 244 fetuses, with median gestational age of 12+2 weeks. The initial number was nine (one case), eight (one case), seven (three cases), six (11 cases), five (eight cases), and four (27 cases). Nuchal translucency was utilized prior to the procedure starting in 1996. The technique was transabdominal ultrasound-guided and intrathoracic injection of potassium chloride. One pregnancy (with seven fetuses) was reduced to three, 42 to two, and four (starting with four fetuses) to singletons. There were ten pregnancy losses (20.4%). A decreasing trend in losses was evident over the 20-year time period: 7/23 (30.4%) from 1994 to 2004 down to 3/26 (11.5%) for 2004-2014. No chromosomal abnormalities were present in any of the survivors. The ethical issues focus on the justification of SF in high-order multifetal pregnancies. CONCLUSION: In this series, pregnancy loss decreased with operator experience. Excellent outcomes can be achieved with the ethically justified use of feticide in high-order multiple pregnancies.

Monochorionic quadramniotic and triamniotic pregnancies following single embryo transfers: two case reports and a review of the literature.

PURPOSE: The purpose of this study is to report two cases of monozygotic quadruplet and triplet pregnancies following single embryo transfer (ET). METHODS: A 29-year-old woman and a 34-year-old woman underwent ART treatment in two affiliated University based ART units. The first woman underwent ICSI with day 3 embryo biopsy for pre-implantation genetic diagnosis (PGD) followed by day 4 transfer, which resulted in a monochorionic quadramniotic (MCQA) quadruplet pregnancy. The second woman underwent conventional IVF with transfer of a single blastocyst, which resulted in a monochorionic triamniotic (MCTA) triplet pregnancy. RESULTS: The first patient underwent successful selective foetal reduction at 16 + 3 and 17 + 4 weeks of gestation. Two healthy twin girls were delivered by elective caesarean section at 35 + 6 weeks of gestation. The second patient underwent successful selective foetal reduction at 14 + 1 weeks of gestation. The remaining monochorionic diamniotic (MCDA) twins are well at the time of writing this article. CONCLUSIONS: To our knowledge, these cases represent the first case of viable MCQA pregnancy following single ET in the world and the third case of a viable MCTA pregnancy following conventional IVF with single ET. Several factors including blastocyst stage transfer and zona pellucida manipulation have been thought to contribute to monozygotic twinning in the context of ART. These two cases add to the growing literature of monozygotic multiple pregnancies following ART.

Outcomes of expectantly managed pregnancies with multiple gestations and preterm premature rupture of membranes prior to 26 weeks.

OBJECTIVE: The objective of the study was to determine the obstetric and neonatal outcomes of expectantly managed multifetal pregnancies complicated by early preterm premature rupture of membranes (PPROM) prior to 26 weeks. STUDY DESIGN: This was a retrospective cohort of all multifetal pregnancies complicated by documented PPROM occurring before 26 0/7 weeks and managed expectantly by a single maternal-fetal medicine practice between July 4, 2002, and Sept. 1, 2013. Neonatal and maternal outcomes were assessed and comparisons made between the fetus with ruptured membranes and the first fetus to deliver with intact membranes. RESULTS: Twenty-three pregnancies (46 fetuses) were analyzed with a median gestational age at PPROM of 22.9 weeks; 74% experienced PPROM at less than 24 weeks' gestation. A median latency of 11 days was achieved with expectant management. Of the 46 neonates, 20 (43%) survived to hospital discharge. Of these, 12 (60%) experienced severe neonatal morbidity defined as defined as grade III or IV intraventricular hemorrhage, bronchopulmonary dysplasia, pulmonary hypoplasia, necrotizing enterocolitis requiring surgical intervention, and/or grade 3 or 4 retinopathy of prematurity. Eight neonates survived to hospital discharge without severe neonatal morbidity. The multiple with ruptured membranes was more likely to experience intrauterine demise but otherwise had similar outcomes as the multiple with intact membranes. Maternal morbidity was considerable, with 7 of 23 pregnancies (30%) complicated by clinical chorioamnionitis, 12 of 23 (52%) delivering by cesarean, of which 3 of 12 (25%) were classical cesarean deliveries. CONCLUSION: Overall, neonatal survival to hospital discharge was 43%, but only 17% survived without significant neonatal morbidity. These data provide a basis for counseling and management of women with multifetal gestation complicated by very early PPROM.

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.

Quadruplet pregnancy complicated by ovarian hyperstimulation syndrome with spontaneous ovulation.

Ovarian hyperstimulation syndrome (OHSS) commonly occurs as a complication of ovarian stimulation with gonadotrophins. Spontaneous OHSS is an extremely rare event, but can occur as a result of stimulation with pregnancy-derived hCG. We herein report a case of quadruplet pregnancy complicated by OHSS with spontaneous ovulation. The patient had previously undergone ovarian stimulation with clomiphene citrate plus FSH. After that, she conceived spontaneously and developed OHSS after three weeks of amenorrhea. The OHSS was managed by conservative treatment and improved at six weeks of gestation. However, a quadruplet pregnancy became apparent on ultrasound examination. The patient therefore elected to have an induced abortion. Besides the conception in the cycle without administration of exogenous gonadotrophins, the symptoms in this case had the same kinetics as iatrogenic OHSS caused by ovarian stimulation.

Multifetal pregnancies: preterm admissions and outcomes.

OBJECTIVE: To describe the rates of antenatal hospital admission during twin or higher order multifetal pregnancies, and the admission outcomes as discharge undelivered, transfer to higher care, or spontaneous or elective delivery. METHODS: Cohort study using linked birth and hospital data. The cohort comprised women who gave birth to twins or higher order multiple infants of≥24 weeks gestation in 2001-2008 and who were admitted to hospital in weeks 20-36 of the pregnancy. RESULTS: In 63.4% of 10 779 twin pregnancies and 99.5% of 197 triplet and quadruplet pregnancies, the woman was admitted to hospital at least once in weeks 20-36 of the pregnancy, for a total 10 985 admissions. Almost half the admissions (46.3%) ended in discharge without delivery, 10.7% in transfer to higher care, 21.1% in spontaneous labour and birth, and 21.8% in elective delivery (induction or prelabour Caesarean section). The reason for admission was preterm labour in 34.2% of admissions. CONCLUSIONS: Hospital admission during pregnancy is common for women with multifetal pregnancies, with many of these admissions resulting in preterm birth. This is the first study to report the rate of pregnancy admissions for women with multifetal pregnancies, and provides a baseline for future studies of hospital use in this population.

Dichorionic quadruplet pregnancy comprising monozygotic triplets and singleton after intracytoplasmic sperm injection and transfer of two fresh embryos: a case report.

Monozygotic triplet pregnancies are very rare in assisted reproductive technology, and the relationship between monozygotic multiple pregnancies and several assisted reproductive techniques, including blastocyst transfer, remains unclear. Here, the case of a 28-year-old female patient with dichorionic quadruplet pregnancy following intracytoplasmic sperm injection and transfer of two day-3 fresh embryos, without assisted hatching, is reported. At 7 weeks following embryo transfer, the dichorionic quadruplet pregnancy, comprising monozygotic monochorionic triamniotic (MCTA) triplets plus a singleton, was detected by a transabdominal ultrasound scan. After counselling, the patient underwent selective reduction of the MCTA triplet pregnancy at 7 weeks after embryo transfer. The remaining singleton pregnancy was uneventful, resulting in a live birth at 38+ weeks. As the predictors of monozygotic multiple gestations remain poorly characterized, clinicians and patients should give great consideration to the risks associated with monozygotic multiple pregnancies, even if the patient has not undergone blastocyst transfer.

Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations.

OBJECTIVE: To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies. METHODS: We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort. RESULTS: Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies. CONCLUSION: Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations.

Management of Quadruplet Pregnancy: A Case Report.

Quadruplet pregnancy is a pregnancy state where four fetuses grow simultaneously inside a mother's womb. Four fetuses developing in a womb is a challenge not only to the mother but to the obstetrician who has to calculate every risk associated with such pregnancy. High order pregnancy is considered a high risk pregnancy due to increase in maternal, fetal and neonatal morbidity and mortality. So a multidisciplinary approach with early involvement of neonatologists and anesthesiologists for the assessment of such case is essential for a successful obstetric outcome. Here we present a case report of 27 years G3P1L1A1 at 33 weeks 2 days of gestation with quadruplet pregnancy with previous lower segment Cesarian section with history of ovulation induction, delivered successfully via cesarean section with successful outcome of all 1 female and 3 male babies. Keywords: case report; cesarean section; fertility agent; multiple pregnancy; pregnancy; quadruplets.

Quadruple pregnancy after post-IVF/ICSI transfer of blastocysts.

Clinical case of a quadruple pregnancy (monochorionic diamniotic and dichorionic diamniotic) after the transfer of two blastocysts generated by intracytoplasmic sperm injection (ICSI). This is the case of a 29-year-old woman patient with transfer of two blastocysts after long cultivation of 6 embryos generated by ICSI and vitrified on day +3. This revealed quadruple clinical pregnancy (monochorionic diamniotic and dichorionic diamniotic) of 56 days of evolution by transvaginal ultrasound. The couple decided to undergo a selective embryonic reduction of the monochorionic diamniotic pregnancy after receiving information about the risks arising from it. After that embryonic reduction the uncomplicated pregnancy continued until 36 weeks of gestation, achieving reproductive success with the birth of two babies alive and healthy.