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.

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.

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.

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.

All for One and One Delivery Room Approach for All?

Multiple births are increasing in frequency related to advanced maternal age and fertility treatments, and they have an increased risk for congenital anomalies compared to singleton births. However, twins have the same congenital anomalies <15% of the time. Thus, having multiple births with discordant anomalies is a growing challenge for neonatologists. Although external anomalies can often be spotted quickly at delivery or sex differences between multiples can rapidly identify those with internal anomalies described on prenatal ultrasound, we present a case of male multiples, who would optimally receive different initial resuscitation strategies on the basis of the presence or absence of an internal anomaly. The similar size of 4 extremely preterm quadruplets raises concern for whether accurate, immediate identification of 1 neonate with a congenital diaphragmatic hernia will be reliable in the delivery room. Clinicians discuss the ethical considerations of an "all for one" approach to this resuscitation.

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.

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.

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.

A rare case of heterotopic quintuplets pregnancy.

OBJECTIVE: We report a rare case of heterotopic pregnancy and high-order pregnancy occurring simultaneously following the use of the assisted reproductive technique (ART). CASE REPORT: A 29-year-old woman, Gravida 2 Para 1, became pregnant after receiving intrauterine insemination (IUI). She came to our emergency room due to diffuse low abdominal pain at seven weeks of gestational age. Transabdominal sonography (TAS) revealed a quadruplet intrauterine pregnancy with an enlarged left adnexa and intrapelvic fluid accumulation. Simultaneous occurrence of high-order pregnancy and left tubal pregnancy with internal hemorrhage was suspected. The patient received an emergent laparoscopic resection of the affected Fallopian tube and recovered well for the remaining hospitalization course. Afterwards, she received fetal reduction procedure and eventually gave birth to twin babies. CONCLUSION: Gynecologist should increase the awareness of heterotopic pregnancy in patients receiving ART. On the other hand, reproductive endocrinologist should reduce the risk of high-order pregnancy without compromising pregnancy rate.

Gestación cuádruple: reporte de caso y revisión de la literatura / Quadruplet pregnancy: case report and review of the literature

RESUMEN Objetivo: Reportar un caso de embarazo cuádruple y revisar la literatura disponible con respecto a la edad gestacional en la que se identifica el tipo de placenta (mono o policoriónica) en la que finaliza el embarazo, el peso del recién nacido y la frecuencia del cuidado prenatal de este tipo de gestaciones. Materiales y métodos: Se presenta del caso de una mujer con embarazo cuádruple secundario a técnica de reproducción asistida, atendida en una institución de cuarto nivel de complejidad, ubicada en la ciudad de Bucaramanga, Colombia. Se realizó una revisión de la literatura publicada en las bases de datos Medline vía PubMed, Embase, SciELO y UptoDate® con los términos de búsqueda: "embarazo múltiple", "cuádruples", "atención prenatal" y "resultado perinatal". La búsqueda se limitó por idioma (artículos en inglés y español). Resultados: Se recuperaron 19 referencias que cumplían con los criterios de inclusión y de exclusión. No hay información sobre la frecuencia con la que se debe hacer el control prenatal. El tipo de placenta se pudo establecer entre las semanas 9 y 25; la edad gestacional varió entre 26 y 34 semanas. El peso varió entre 1.076 y 1.770 g. Los embarazos multigestación se acompañan frecuentemente de complicaciones maternas y perinatales. Conclusiones: El diagnóstico del embarazo cuádruple puede hacerse temprano en la gestación. Frecuentemente se acompaña de prematuridad y bajo peso al nacer. Se requieren estudios que evalúen el manejo más seguro y efectivo de esta condición.

ABSTRACT Objective: To report the case of a quadruplet pregnancy and conduct the review of the available literature regarding gestational age at which the type of placenta (monochorionic or polychorionic) is identified, the gestational age at which the pregnancy comes to an end, the weight of the neonate, and the frequency of prenatal care in this type of gestation. Materials and methods: Case report of a woman with a quadruplet pregnancy secondary to assisted reproduction technique, seen at a Level IV complexity centre in the city of Bucaramanga, Colombia. A review of the literature was conducted in Medline vía PubMed, Embase, SciELO and UptoDate® databases using the search terms "multiple pregnancy," "quadruplets," "prenatal care," and "perinatal outcome". The search was limited by language to articles in English and Spanish. Results: Overall, 19 references that met the inclusion and exclusion criteria were retrieved. There is no information on the required frequency of prenatal visits. It was possible to identify the type of placenta between 9 and 25 weeks; gestational age varied between 26 and 34 weeks. Weight varied between 1,076 and 1,770 g. Multigestation pregnancies are frequently associated with maternal and perinatal complications. Conclusions: Quadruplet pregnancies may be diagnosed early in the gestation. They are frequently associated with prematurity and low birth weight. Further studies are required in order to assess the safest and most effective way of managing this condition.

Complete Hydatidiform Mole Coexisting with Three Viable Fetuses in a Quadruplet Pregnancy.

We hereby report a case of quadruplet pregnancy with delivery of 3 viable infants and a complete mole. This was an induced conception with clomiphene citrate. At 22 weeks, cystic structures were noticed in one of the placentae and a suspicion of co-existant molar pregnancy was made. The case discussed with oncologist and pregnancy was continued with close monitoring of &beta;-hCG and Ultrasound. Her &beta;-hCG at 23 weeks was 748 mIU/ml, which continued to rise until the 29th week of gestation to a level of 305881.68 mIU/ml and declined gradually thereafter. Similarly, hydropic change in placenta also continued to increase progressively. She was given steroid cover at 32 weeks and delivery was aimed at 34 weeks of gestation. The patient went into preterm labour at 33 weeks and 3 female infants delivered by lower segment cesarean section (LSCS) followed by removal of 3 placentae along with copious molar tissue at the end. The newborns were kept in the nursery, non-requiring assisted ventilation and discharged in satisfactory condition. The histopathologyand immunohistochemistry confirmed the diagnosis of a quadruplet pregnancy comprising of one complete mole with 3 normal placentae.

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.

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.