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Contents: Original Research

Obstetric and Perinatal Outcomes in Pregnancies Conceived After Preimplantation Genetic Testing for Monogenetic Diseases

Feldman, Baruch MD, PhD; Orvieto, Raoul MD; Weisel, Marine MD; Aizer, Adva PhD; Meyer, Raanan MD; Haas, Jigal MD; Kirshenbaum, Michal MD

Author Information
doi: 10.1097/AOG.0000000000004062

Preimplantation genetic testing, previously termed preimplantation genetic diagnosis, involves the use of assisted reproductive technologies (ART) for the genetic diagnosis of embryos to enable the birth of healthy children in families that are at high risk of transmitting inherited disease to the offspring and to avoid the termination of pregnancy in case of an affected fetus or the birth of an affected child. The main indications for preimplantation genetic testing are specific monogenic aberrations and sex-related disorders and structural chromosomal imbalances, as well as aneuploidy screening.1,2

Preimplantation genetic testing is based on ART treatment, which includes ovarian stimulation, oocyte retrieval, fertilization of the ovum by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), and DNA extraction, which can be obtained during the cleavage stage, where one or two blastomeres are extracted, or by blastocyst biopsy, in which few cells from the trophectoderm are extracted.2,3 In contrast to preimplantation genetic testing with aneuploidy screening, which applies next-generation sequencing on a blastocyst trophectoderm biopsy, preimplantation genetic testing for monogenic diseases is based on single blastomere testing, with polymerase chain reaction as the method of choice for amplifying the small DNA content.4 The unaffected embryos are transferred back to the uterus or vitrified for future transfers.5

It is well established that pregnancies conceived after ART are associated with higher rates of obstetric and neonatal complications compared with spontaneously conceived pregnancies. Previous data have shown that pregnancies conceived with IVF or ICSI are at an increased risk of preterm delivery, preterm prelabor rupture of membranes, placenta previa, placental abruption, hypertensive disorders of pregnancy, and small-for-gestational-age (SGA) newborns.6–10

The higher risk of obstetric and neonatal complications in pregnancies conceived by ART might originate from the underlying infertility itself, the higher prevalence of multiple pregnancies, or the use of artificial interventions and external manipulations, for example, culture media, the duration of time in culture, the freezing and thawing procedures, or manipulation of gametes and embryos. Because couples undergoing ART treatment for preimplantation genetic testing for monogenic diseases are generally fertile and can conceive spontaneously, their alternative is natural conception and prenatal genetic diagnosis. For these couples, choosing preimplantation genetic testing for monogenic diseases might add further risks inherent in the ART-associated invasive manipulation, such as IVF or ICSI procedures and embryo biopsy.

To date, several studies have reported on the obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic testing for monogenic diseases, with inconsistent results,10–13 and it is still unclear whether the manipulation of embryo biopsy has additional obstetric and neonatal risks compared with pregnancies conceived with IVF without preimplantation genetic testing for monogenic diseases (infertile couples) or spontaneous conceptions. Nevertheless, information regarding these outcomes is crucial for health care professionals and patients who desire IVF with preimplantation genetic testing for monogenic diseases in the absence of infertility.

Prompted by the aforementioned information, we present our experience with preimplantation genetic testing for monogenic diseases using day-3 blastomere biopsy. Our aim was to asses and compare the obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic testing for monogenic diseases with those conceived after IVF with no preimplantation testing or spontaneously, aiming to control for the embryo biopsy and the ART procedure, respectively.

METHODS

The study population included all pregnancies achieved after preimplantation genetic testing for monogenic diseases from January 2006 to August 2018 at the Sheba Medical Center, a tertiary care medical center located in Ramat-Gan, Israel. Preimplantation genetic testing with aneuploidy screening cycles was excluded.

Ovarian stimulation, IVF or ICSI, zona pellucida laser breaching, blastomere biopsy, polymerase chain reaction technique, and embryo culture were carried out as previously described.14 Embryos underwent biopsy on day 3 and were transferred a day later in cases of available, unaffected embryos. We transferred one to two embryos, depending on patients' characteristics (patient's age, ovarian reserve, and previous IVF cycles). Surplus unaffected embryos were cryopreserved and transferred in a subsequent cycle, if required. As per our center policy, all patients undergoing preimplantation genetic testing for monogenic diseases were offered prenatal genetic testing by chorionic villus sampling or amniocentesis for confirmation of the preimplantation testing and other screening genetic testing, depending on the couples' choice.

The PGT-M group is the cohort of pregnant patients who underwent preimplantation genetic testing for monogenic diseases. For this group, we prospectively collected information including the couples' demographic and clinical background, ART protocol and characteristics, and, if patients conceived, their obstetric and neonatal outcomes. Biochemical pregnancy was defined as a positive β-hCG test 14 days after embryo transfer without identification of pregnancy on ultrasound scan at 6–7 weeks of gestation. Clinical pregnancy was defined as intrauterine gestational sac seen on ultrasound scan at that time. Pregnancy outcome was defined as 1) abortion, if a pregnancy ended before 20 weeks of gestation; 2) stillbirth, if intrauterine fetal death occurred beyond 20 weeks of gestation, or 3) live birth. Pregnancies in which loss of fetus occurred or reduction of fetus(es) was done were categorized according to the number of fetuses in the ongoing pregnancy.

Pregnancies in the study cohort that resulted in live births were compared with pregnancies conceived with IVF with no preimplantation genetic testing (IVF group) or spontaneously (spontaneous conception group) and delivered at the Sheba Medical Center. The selection of the control groups was done by including all women who gave birth during the month of May from 2006 to 2018. Information about obstetric and neonatal outcomes was retrieved from our institutional computerized data system. The obstetric and perinatal outcomes included the prevalence of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy, preterm delivery before 37 and 34 weeks of gestation, SGA, neonatal intensive care unit administrations, and the number of neonatal hospitalization days. Hypertensive disorders of pregnancy were defined as preeclampsia (new-onset hypertension and proteinuria or hypertension and significant end-organ dysfunction with or without proteinuria in the last half of pregnancy or postpartum) or gestational hypertension (hypertension without proteinuria or other signs or symptoms of preeclampsia-related end-organ dysfunction that developed after 20 weeks of gestation).15 Small for gestational age was defined as neonatal weight less than the 10th percentile according to gestational age using population-based growth curves for singletons and twins.

Statistical analysis was conducted with SPSS 25.0 and Excel software. For all three groups, categorical variables are presented as number of cases and percentage. Comparison of categorial variables among groups was analyzed by χ2 test or Fisher exact test, as appropriate. Continuous data are presented as mean and SD or median and interquartile range depending on normality test, as appropriate. Comparison of continuous variables was performed by one-way analysis of variance followed by t test or Kruskal-Wallis followed by Mann-Whitney test, as appropriate.

To further examine the association between covariates and the obstetric and neonatal outcomes, we used a multivariate regression model accounting for the following variables: age, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), current smoking habits, parity, and mode of conception. In the PGT-M group, a multivariable analysis was conducted to assess the effect of ART methods and the indication for preimplantation genetic testing for monogenic diseases on obstetric outcomes. Effect estimates were reported as odds ratios (ORs) with 95% CIs. P<.05 was considered statistically significant.

The study was approved by the Sheba Medical Center institutional review board in accordance with national regulations.

RESULTS

From January 2006 to August 2018, 881 couples underwent 2,603 ART treatment cycles, which included oocyte retrieval and day-3 blastomere biopsies. These treatment cycles resulted in 643 pregnancies, of which 129 (20%) were biochemical pregnancies, seven (1%) were ectopic pregnancies, and 507 (79%) were ongoing clinical pregnancies (400 singleton, 100 twin, and seven triplet pregnancies) (Fig. 1). Of the 643 pregnancies conceived after preimplantation genetic testing for monogenic disease, 341 resulted from ICSI procedures, 361 resulted from fresh embryo transfer, and, in 380 pregnancies, the indication for preimplantation genetic testing was maternal monogenic disease.

Fig. 1.
Fig. 1.:
Flow chart of included pregnancies with preimplantation genetic testing for monogenic diseases. *Pregnancies initiated as singleton (n=323) and twin (n=20) or triplet (n=2) pregnancies that continued as singleton. Pregnancies initiated as twin (n=73) and triplet pregnancies that continued as twin (n=3).Feldman. Preimplantation Genetic Testing and Obstetric Outcome. Obstet Gynecol 2020.

Of the 400 singleton pregnancies, 60 (15%) resulted in spontaneous abortions—58 during the first trimester and two in the early second trimester. Two pregnancies resulted in intrauterine fetal death during the third trimester. Fifteen women (3.7%) had termination of pregnancy: eight owing to genetic abnormalities not related to the known preimplantation genetic testing and seven owing to major malformations detected by prenatal ultrasound examination.

Of the 100 twin pregnancies, six (6%) resulted in spontaneous abortion of both fetuses during the first trimester. Termination of pregnancy was done in one case owing to cystic hygroma detected in both fetuses. Fetal loss of one twin occurred in 15 pregnancies (15%), one pregnancy was heterotopic, and four patients underwent fetal reduction to singleton pregnancy.

Of the seven triplet pregnancies, two resulted in spontaneous abortion of one fetus; two had a reduction to singleton pregnancy and one to twin pregnancy.

Overall, the PGT-M group included 423 pregnancies that ended in live births: 345 singleton pregnancies, 76 twin pregnancies, and two triplet pregnancies. The control groups included 5,290 singleton pregnancies and 92 twin pregnancies in the spontaneous conception group and 422 singleton pregnancies and 101 twin pregnancies in the IVF group.

Maternal age was similar between women in the PGT-M and spontaneous conception groups (but was higher in the IVF group.) There were more primiparous women in the PGT-M and IVF groups than in the spontaneous conception group (Tables 1 and 2).

Table 1.
Table 1.:
Basic Characteristics and Obstetric and Neonatal Outcomes in Singleton Pregnancies
Table 2.
Table 2.:
Basic Characteristics and Obstetric and Neonatal Outcomes in Twin Pregnancies

Table 1 and Figure 2 present the obstetric and neonatal outcomes of singleton pregnancies in the three groups. The rate of hypertensive disorders of pregnancy was higher in the PGT-M group compared with the spontaneous conception group (6.9% vs 2.3%; OR 3.1; 95% CI 1.9–4.9) and the IVF group (6.9% vs 4.7%; OR 1.5; 95% CI 0.8–2.7). A multivariable regression analysis shows that the factors associated with hypertensive disorders were preimplantation genetic testing for monogenic diseases (PGT-M vs spontaneous conception group: adjusted odds ratio [aOR] 14.8; 95% CI 7.4–29.8; PGT-M vs IVF group: aOR 5.9; 95% CI 1.9–18.2), maternal age (aOR 1.04; 95% CI 1.01–1.07), and previous deliveries (aOR 0.49; 95% CI 0.2–0.8) (Table 3). Likewise, the rate of SGA was higher in the PGT-M group compared with the spontaneous conception group (12.4% vs 3.9%; OR 3.4; 95% CI 2.4–4.9) and the IVF group (12.4 vs 4.5; OR 3; 95% CI 1.7–5.2). A multivariable regression analysis revealed that the statistically significant factors associated with SGA were preimplantation genetic testing for monogenic diseases (PGT-M vs spontaneous conception group: aOR 2.3; 95% CI 1.5–3.4; PGT-M vs IVF group: aOR 2.5; 95% CI 1.2–5), BMI (aOR 0.98; 95% CI 0.97–0.98), and smoking (aOR 2.1; 95% CI 1.4–3.2) (Table 3). The percentage of preterm deliveries before 37 weeks of gestation was higher in the PGT-M group compared with the spontaneous conception group (10.1% vs 6.4%; aOR 1.6; 95% CI 1.1–2.4), although not different from the IVF group (10.1% vs 11.3%, aOR 0.85; 95% CI 0.5–1.35). The rate of gestational diabetes mellitus was lower in the PGT-M group compared with the IVF group (9.2% vs 15.6%; aOR 0.55; 95% CI 0.3–0.8).

Fig. 2.
Fig. 2.:
Obstetric and neonatal outcome in singleton pregnancies. Arrows represent significant differences. GDM, gestational diabetes mellitus; NICU, neonatal intensive care unit; PGT-M, preimplantation genetic testing for monogenic disease; IVF, in vitro fertilization.Feldman. Preimplantation Genetic Testing and Obstetric Outcome. Obstet Gynecol 2020.
Table 3.
Table 3.:
Multivariable Regression Model for Covariates Associated With Hypertensive Diseases or Small for Gestational Age in Singleton Pregnancies

The cesarean delivery rate, elective or emergent, was not different between the PGT-M and spontaneous conception groups (27.8% vs 23%; OR 0.9; 95% CI 0.8–1.2), but it was significantly higher in the IVF group (40.7%; OR 0.56; 95% CI 0.4–0.7). The neonatal outcomes did not significantly differ between the PGT-M group and the spontaneous conception or IVF groups.

Of the 345 newborns from singleton pregnancies in the PGT-M group, there was one neonatal death owing to prematurity complications. Five neonates were diagnosed with genetic abnormalities not related to the indication for preimplantation genetic testing for monogenic diseases (one occurrence each of trisomy 21, Beckwith-Wiedemann syndrome, hemophilia A, new mutation of neurofibromatosis 1, and ocular albinism). Eleven neonates had minor structural anatomic abnormalities, five of which were related to the genitourinary system. Complete data regarding congenital malformations in the IVF and spontaneous conception groups were not available.

Table 2 and Figure 3 present the obstetric and neonatal outcomes of twin pregnancies in the three study groups. Gestational age at delivery and the preterm birth rate were not different among the three study groups. The rate of hypertensive disorders of pregnancy was higher in the PGT-M group compared with the spontaneous conception group (15.7% vs 4.3%; OR 4.1; 95% CI 1.8–13.3) and the IVF group (15.7% vs 4.3%; OR 4.5; 95% CI 1.4–14). A multivariable regression analysis revealed that the only statistically significant factor associated with hypertensive disorders was preimplantation genetic testing for monogenic diseases (PGT-M vs spontaneous conception group: aOR 10.9; 95% CI 2.3–50; PGT-M vs IVF group: aOR 3.7 95% CI 1.1–12.8) (Table 4). The cesarean delivery rate was higher in the PGT-M group compared with the spontaneous conception group (OR 2.6; 95% CI 1.3–5), but not different from that in the IVF group. Other obstetric complication rates were not different between the PGT-M group and the spontaneous conception or IVF group.

Fig. 3.
Fig. 3.:
Obstetric and neonatal outcome in twin pregnancies. Arrows represent significant differences. GDM, gestational diabetes mellitus; NICU, neonatal intensive care unit; PGT-M, preimplantation genetic testing for monogenic disease; IVF, in vitro fertilization.Feldman. Preimplantation Genetic Testing and Obstetric Outcome. Obstet Gynecol 2020.
Table 4.
Table 4.:
Multivariable Regression Model for Covariates Associated With Hypertensive Diseases in Twin Pregnancies

Of the 152 newborn twins from the PGT-M group, there were two cases of neonatal death; one was due to trisomy 18, and one was due to complications of extreme prematurity. One neonate was born with bilateral clubfoot, and one neonate was diagnosed postnatally with congenital temporal infarct.

A subanalysis of women in the PGT-M group revealed that the indication for preimplantation genetic testing, the mode of fertilization (ICSI vs IVF), and the type of embryo transfer (fresh vs frozen) did not affect the obstetric or neonatal outcomes (Appendices 1 and 2, available online at http://links.lww.com/AOG/C25).

DISCUSSION

In this study, we found a higher risk of several obstetric adverse outcomes among pregnancies conceived after prenatal genetic testing for monogenic diseases compared with spontaneously conceived pregnancies and pregnancies conceived with IVF without prenatal genetic testing.

Couples predisposed to genetically abnormal pregnancies owing to inherited familial genetic disorders can choose the use of IVF and preimplantation genetic testing for monogenic diseases but usually do not have fertility difficulties; therefore, conceiving naturally and using prenatal genetic tests is a plausible option. To be able to make a rational decision, these couples should be informed about the inherent potential risks associated with the preimplantation genetic testing for monogenic diseases procedure. Despite the increasing use of preimplantation genetic testing for monogenic diseases, there are only a few studies that investigated obstetric outcome of these pregnancies, with inconsistent results.10–12,16–18 Some of these previous studies compared pregnancies conceived after preimplantation genetic testing for monogenic diseases with pregnancies conceived with IVF without preimplantation genetic testing to control for the effect of embryo biopsy on obstetric and neonatal complications.11,17–19 Nonetheless, given that most patients who undergo preimplantation genetic testing for monogenic diseases are fertile and that their alternative to preimplantation genetic testing for monogenic diseases is natural conception and prenatal genetic diagnosis, outcomes of pregnancies with preimplantation genetic testing for monogenic diseases should also be compared with outcomes of spontaneously conceived pregnancies.

One of our most noteworthy findings is the significant increased risk of hypertensive disorders associated with pregnancies conceived after preimplantation genetic testing for monogenic diseases compared with both pregnancies conceived with IVF without preimplantation genetic testing and spontaneously conceived pregnancies, a difference that persisted even after stratification to singleton and twin pregnancies. In addition, we noted an increased risk of SGA among singleton pregnancies conceived after preimplantation genetic testing for monogenic diseases compared with both singleton spontaneously conceived pregnancies and singleton pregnancies conceived with IVF without preimplantation genetic testing. These two placenta-related complications may be associated with the additional embryo biopsy required for preimplantation genetic testing for monogenic diseases and its interference with subsequent normal placentation. On the other hand, the ART method (IVF vs ICSI), the type of embryo transfer, and the maternal indication for preimplantation genetic testing for monogenic diseases did not affect the risk of hypertensive disorders or SGA.

Zhang et al17 compared the outcomes of 180 pregnancies conceived after preimplantation genetic testing with 177 pregnancies conceived with IVF without preimplantation genetic testing and, in agreement with our observations, demonstrated a threefold increase in the odds of preeclampsia in pregnancies with preimplantation genetic testing. Similarly, Desmyttere et al and Liebaers et al have also observed higher risks of obstetric complications in pregnancies with preimplantation genetic testing compared with pregnancies resulting from IVF or ICSI without preimplantation genetic testing, including hypertensive disorders and SGA, respectively.18,19 On the other hand, other previous studies did not find a higher rate of SGA among pregnancies conceived after preimplantation genetic testing compared with pregnancies conceived with IVF without preimplantation genetic testing or spontaneously conceived pregnancies.12,13,16 These studies did not report the rate of hypertensive disorders. This inconsistency might be a result of embryo biopsy at different stages of development. Although the higher risk of hypertensive disorders among pregnancies conceived after preimplantation genetic testing for monogenic diseases compared with spontaneously conceived pregnancies might be explained by the IVF or ICSI procedure,6 the higher rate compared with pregnancies conceived with IVF without preimplantation genetic testing suggests that the embryo biopsy itself might be the culprit of abnormal placentation. The latter is even more noticeable in light of the higher tendency of the patients with pregnancies conceived with IVF without preimplantation genetic testing to develop hypertensive disorders of pregnancy owing to their known risk factors, such as advanced maternal age and infertility itself.

The higher rate of preterm delivery among patients in the PGT-M group compared with those in the spontaneous conception group may be a result of several causes. Nonetheless, we should differentiate iatrogenic or medically indicated preterm birth and spontaneous preterm birth, which are both more common in women who conceive after preimplantation genetic testing for monogenic diseases than in those who conceive naturally.12 The higher rate of obstetric complications in the PGT-M group might be related to the increased need for early induction of labor and thus delivery before 37 weeks of gestation. In addition, previous studies have suggested that the risk of preterm birth is a result of the treatment itself, which leads to abnormal placentation.20 Similar to previous studies that compared pregnancies with preimplantation genetic testing with pregnancies conceived with IVF without preimplantation genetic testing, we did not find a difference in the rate of preterm deliveries between these two groups.12,16,19,21

The advantage of our study is the large number of pregnancies conceived after preimplantation genetic testing for monogenic diseases being followed prospectively from the primary preconception consultation through preimplantation genetic testing and pregnancy follow-up. Moreover, the comparison of the same cohort of patients who underwent preimplantation genetic testing for monogenic diseases with patients with both pregnancies conceived with IVF without preimplantation genetic testing and spontaneously conceived pregnancies largely contributes to a better understanding of the etiology of the different obstetric outcomes.

The limitation of our study is the lack of information regarding the mode of fertilization or the type of embryo transfer (whether fresh or frozen embryo transfer) in the IVF control group and subsequently the lack of subanalyses according to those parameters.

In conclusion, we found an increased risk of hypertensive disorders during pregnancy in singleton and multiple pregnancies conceived after preimplantation genetic testing for monogenic diseases and increased risk of SGA in singleton pregnancies conceived after preimplantation genetic testing for monogenic diseases compared with spontaneously conceived pregnancies or pregnancies conceived with IVF without preimplantation genetic testing. In addition, comparable with pregnancies conceived with IVF without preimplantation genetic testing, the risk of preterm labor was higher among singleton pregnancies conceived after preimplantation genetic testing for monogenic diseases compared with spontaneously conceived pregnancies. The risks of other obstetric and neonatal complications were not different between pregnancies conceived after preimplantation genetic testing for monogenic diseases and spontaneously conceived pregnancies.

REFERENCES

1. Thornhill AR, deDie-Smulders CE, Geraedts JP, Harper JC, Harton GL, Lavery SA, et al. ESHRE PGD Consortium best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Hum Reprod 2005;20:35–48.
2. Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, et al. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update 2012;18:234–47.
3. Harper JC, Sengupta SB. Preimplantation genetic diagnosis: state of the ART 2011. Hum Genet 2012;131:175–86.
4. De Rycke M, Goossens V, Kokkali G, Meijer-Hoogeveen M, Coonen E, Moutou C. ESHRE PGD Consortium data collection XIV-XV: cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013. Hum Reprod 2017;32:1974–94.
5. Grace J, El Toukhy T, Braude P. Pre-implantation genetic testing. BJOG Int J Obstet Gynaecol 2004;111:1165–73.
6. Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update 2012;18:485–503.
7. Crosignani PG, Bonduelle V, Braude P, Collins J, Devroey P, Evers JLH, et al. Intracytoplasmic sperm injection (ICSI) in 2006: evidence and evolution. Hum Reprod Update 2007;13:515–26.
8. McGovern PG, Llorens AJ, Skurnick JH, Weiss G, Goldsmith LT. Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis. Fertil Steril 2004;82:1514–20.
9. Helmerhorst FM. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ 2004;328:261.
10. Bay B, Ingerslev HJ, Lemmen JG, Degn B, Rasmussen IA, Kesmodel US. Preimplantation genetic diagnosis: a national multicenter obstetric and neonatal follow-up study. Fertil Steril 2016;106:1363–9.e1.
11. Sunkara SK, Kamath MS, Antonisamy B. Perinatal outcomes following preimplantation genetic diagnosis versus IVF or ICSI: analysis of 99,498 singleton live births. Hum Reprod 2016;32:432–8.
12. Eldar-Geva T, Srebnik N, Altarescu G, Varshaver I, Brooks B, Levy-Lahad E, et al. Neonatal outcome after preimplantation genetic diagnosis. Fertil Steril 2014;102:1016–21.
13. Hasson J, Limoni D, Malcov M, Frumkin T, Amir H, Shavit T, et al. Obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic diagnosis: cohort study and meta-analysis. Reprod Biomed Online 2017;35:208–18.
14. Feldman B, Aizer A, Brengauz M, Dotan K, Levron J, Schiff E, et al. Pre-implantation genetic diagnosis—should we use ICSI for all? J Assist Reprod Genet 2017;34:1179–83.
15. Gestational hypertension and preeclampsia. ACOG Practice Bulletin No. 222. American College of Obstetricians and Gynecologists. Obstet Gynecol 2020;135:e237–e60.
16. Sunkara SK, Antonisamy B, Selliah HY, Kamath MS. Pre-term birth and low birth weight following preimplantation genetic diagnosis: analysis of 88 010 singleton live births following PGD and IVF cycles. Hum Reprod 2017;32:432–8.
17. Zhang WY, von Versen-Höynck F, Kapphahn KI, Fleischmann RR, Zhao Q, Baker VL. Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertil Steril 2019;112:283–90.
18. Desmyttere S, De Rycke M, Staessen C, Liebaers I, De Schrijver F, Verpoest W, et al. Neonatal follow-up of 995 consecutively born children after embryo biopsy for PGD. Hum Reprod 2012;27:288–93.
19. Liebaers I, Desmyttere S, Verpoest W, De Rycke M, Staessen C, Sermon K, et al. Report on a consecutive series of 581 children born after blastomere biopsy for preimplantation genetic diagnosis. Hum Reprod 2010;25:285–2.
20. Wisborg K, Ingerslev HJ, Henriksen TB. In vitro fertilization and preterm delivery, low birth weight, and admission to the neonatal intensive care unit: a prospective follow-up study. Fertil Steril 2010;94:2102–6.
21. Hassan MAM, Killick SR. Is previous aberrant reproductive outcome predictive of subsequently reduced fecundity? Hum Reprod 2005;20:657–64.
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