Abstract
Objective:
To assess the reproductive and neonatal outcomes of cycles in which donor oocyte embryos were transferred to gestational carriers compared to intended parent recipients.
Design:
Retrospective cohort study.
Setting:
Not applicable.
Patient(s):
Intended parent recipients and gestational carriers receiving donor oocyte embryos in 2014 in the United States.
Interventions(s):
None.
Main Outcomes Measure(s):
Clinical pregnancy, live birth, miscarriage, plurality, prematurity, and birth weight from pregnancies conceived with donor oocyte embryos transferred to either a gestational carrier or an intended parent recipient.
Result(s):
The mean ages of intended parent recipients (N=18,317) and gestational carriers (N=1,927) were 41.6 and 31.6 years, respectively. Compared to an intended parent recipient, patients using a gestational carrier had significantly higher odds of a clinical pregnancy (65.2% vs. 56.3%, adjusted odds ratio (aOR) 1.33, 95% confidence interval (CI) 1.17–1.51) and live birth (57.1% vs. 46.4%, aOR 1.37, 95% CI 1.21–1.55) using fresh or frozen donor-oocyte embryos. Of the singletons born (n=716 using a gestational carrier and n=5,632 in intended parent recipients), the incidence of prematurity was significantly lower in gestational carriers compared to intended parent recipients (17.5% vs. 25.4%, aOR 0.78, 95% CI 0.61–0.99). The incidence of low birthweight among singletons was significantly reduced in gestational carrier cycles (6.4% vs. 12.1%, aOR 0.62, 95% CI 0.44–0.89).
Conclusion:
Intended parent recipients had decreased pregnancy rates and poorer neonatal outcomes compared to a gestational carrier. This suggests that a history of infertility adversely affects the uterine microenvironment, independent of the oocyte.
Keywords: Gestational carrier, intended donor recipient, donor oocyte, reproductive outcome, perinatal outcome
Assisted reproductive technology (ART) has been linked to worse perinatal outcomes relative to spontaneous pregnancy, including increased rates of preterm de livery and low birth weight (1–3). It is unclear if this is an effect of the infertility itself, maternal age, laboratory techniques including fertilization and embryo culture, and/ or supra-physiological hormone levels from ovarian stimulation. The interplay of these variable conditions and their associations with adverse perinatal outcomes are still under debate.
There has been conflicting data regarding the effect of the uterine contribution to adverse perinatal outcomes among women using donor oocytes. Some studies reporting on outcomes of women of advanced age using donor oocytes found that the uterus is not a significant factor in obstetric and neonatal outcomes (4–7). In contrast, other studies reported an increased risk of gestational diabetes, preeclampsia, abnormal placentation, and increased risk of cesarean delivery (8–11). Many of these studies were too small to show absolute risks of neonatal outcomes such as preterm delivery, low birth weight and fetal demise. In addition, the larger multicenter donor oocyte studies reporting on neonatal outcomes were limited due to inappropriate controls such as autologous in vitro fertilization (IVF) and/or spontaneous conception introducing many confounding variables (12–14).
There are no strict guidelines or policies as to the age a woman should be advised against pregnancy. A 2016 American Society for Reproductive Medicine (ASRM) Ethics Committee opinion suggests weighing the risks, benefits, and ethical considerations in allowing women ages 45–54 years to proceed with donor oocyte recipient cycles (15). According to the Center for Disease Control and Prevention (CDC), there were 20,481 ART cycles involving donor eggs or embryos in 2014 in the United States with use going up dramatically at age 40. Among women over the age of 48, 86% of all ART cycles used donor eggs (16). It is increasingly common practice among clinicians to help women of advanced age, including menopausal patients, achieve pregnancy with donor oocytes. Some clinics even allow women ages 60s and 70s years to receive treatment (11, 17). With the widespread use of donor oocytes and the growing acceptance of gestational carriers, women of advanced reproductive age have the option of weighing the significant morbidity associated with pregnancy or arranging a gestational carrier.
To isolate the effects of the uterine environment, we compared reproductive and perinatal outcomes of donor oocyte cycles among gestational carriers and intended parent recipients. Our study on donor oocyte cycles presents a unique situation where all recipients have a similar uterine preparation mimicking the physiology of the menstrual cycle, without the supra-physiologic hormonal environment present in a fresh cycle. In addition, the egg quality of a donor cycle is optimal and implantation rates are higher as they generally come from younger women. This scenario isolates the effects of infertility on reproductive and neonatal outcomes and is the first study to compare the reproductive and perinatal outcomes of donor egg cycles in gestational carriers to intended parent recipients. We hypothesize that intended parent recipients have worse pregnancy outcomes, including higher rates of prematurity and low birthweight.
MATERIALS AND METHODS
The study was approved by the University Hospitals Cleveland Medical Center Institutional Review Board. Data on all gestational carrier cycles and intended parent recipient cycles in the United States utilizing donor oocytes were collected from the 2014 Society for Assisted Reproductive Technologies (SART) database. SART collects anonymous data from approximately 95% of clinics in the United States (18). Variables collected included intended parent’s demographics, smoking status, cycle type, infertility diagnosis, number of embryos transferred, elective single embryo transfer (eSET), assisted hatching, use of preimplantation genetic screening/diagnosis (PGS/PGD), intracytoplasmic sperm injection (ICSI), and treatment outcomes including pregnancy outcome, birth weight, and gestational age at delivery.
Study Outcomes
We considered clinical pregnancy (CP), live birth (LB), miscarriage and plurality as pregnancy outcomes. CP was defined by the presence of a gestational sac. LB was defined as a live born neonate greater than 20 weeks gestation. We also considered preterm delivery (PTD), late PTD, very early PTD, and low birthweight (LBW) as birth outcomes. Gestational age at delivery was calculated using the date of embryo transfer. We defined PTD in 3 ways: live birth delivery at <37 weeks as PTD; ≥32 weeks and <37 weeks as late PTD; and <32 weeks gestation as very early PTD. LBW was defined as a neonate weighing less than 2500 grams.
Statistical Analysis
Demographic and reproductive characteristics were compared between gestational carrier cycles and intended parent recipient cycles using Fisher’s exact tests and chi-square tests for categorical variables and Student’s t-test for continuous variables, as appropriate. Infertility diagnosis and ART factors were also compared by gestational carrier cycles versus intended parent recipient cycles.
Two main analyses were performed: the association between cycle type (gestational carrier vs. intended parent recipient) and pregnancy outcome (CP, LB, miscarriage, and plurality); andthe association between cycle type and birth outcomes (including PTD, late PTD, very early PTD, and LBW) among singleton live births. Each PTD classification was compared to full term deliveries and LBW was compared to normal birth weight. We also investigated associations between cycle type and LBW stratified by gestational age (i.e., among term or preterm neonates). Cycles with no embryo transferred or donor embryos (generated from infertile couples) were excluded from the analysis. Generalized linear regression models with robust error variance to account for multiple cycles for the same woman were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate these associations between cycle type (gestational carrier vs. intended parent recipient) and pregnancy and birth outcomes. Models were adjusted for carrier/recipient age, fresh or frozen embryo transfer, use of preimplantation genetic testing (PGD or PGS), assisted hatching, ICSI, number of embryos transferred. Models for birth outcomes were further adjusted for reduction in fetal hearts.
To isolate the effects of infertility, we performed two sub-group analyses: (1) intended parent recipients with at least one prior live term birth and a history of at least one prior ART cycle compared to gestational carriers and (2) parous intended parent recipients without a history of ART compared to gestational carriers. The SART data do not provide any information on parity in gestational carriers; however, we assumed gestational carriers had at least one prior uncomplicated term delivery, according to the suggested ASRM criteria for selecting potential gestational carrier candidates (19). We also compared percentages of LB, LBW, and PTD from gestational carrier and intended parent recipient cycles by age group categories (i.e., <35, 36–38, 39–41, 42–44, 45–47, 48–50, and 51–53 years); the analysis was restricted to women of age ≤53 due to small number of cycles from women of age greater than 54 and no statistical comparisons were made. All data were analyzed using SAS version 9.4 (SAS Institute, Cary, North Carolina).
RESULTS
In 2014, there were a total of 21,391 cycles using donor oocytes. Of these, 1,067 canceled cycles and 80 cycles with a simultaneous autologous embryo transfer were excluded. As a result, the analysis included 20,244 donor oocyte cycles, of which 1,927 were gestational carrier cycles and 18,317 were intended parent recipient cycles. The oocyte donor age ranged from 18 to 50, with a mean age of 26.2 (Table 1). The largest percentage of intended parent recipients were 41–45 years old (44.2%), with a mean age of 41.6. Most gestational carriers were under 35 years old (78.3%) with a mean age of 31.6. Most of the intended parents were non-Hispanic white, nonsmokers, and had performed 2.3 prior ART cycles. Gestational carrier cycles had significantly more frozen-thaw embryo transfers compared to intended parent recipient cycles (61% vs 41.9%, P<.0001). Intended parents using a gestational carrier had a diagnosis of uterine infertility and diminished ovarian reserve in 17.6% and 46% of cycles, respectively. Of note, 52% of cycles reported “other” for the infertility diagnosis. Intended parent recipients had a diagnosis of diminished ovarian reserve in 78.8% of cases. Among cycles using a gestational carrier, 31% used PGS/PGD and 74.4% had an eSET. In cases of intended parent recipients, only 12% utilized PGS/PGD and 78.5% transferred a single embryo (Table 1).
TABLE 1.
Characteristics of donor oocyte cycles among patients with and without a gestational carrier, 2014 Society for Assisted Reproductive Technologies data.
| Variable | Gestational carrier cycles | Intended parent recipient cycles | P value |
|---|---|---|---|
| No. of cycles | 1,927 | 18,317 | |
| Donor cycle type, n (%) | |||
| Fresh | 754 (39.1) | 10,657 (58.2) | < .0001 |
| Thawed embryo | 1,176(61.0) | 7,670 (41.9) | < .0001 |
| Thawed oocyte | 110(5.7) | 2,528(13.8) | < .0001 |
| Patient factors | |||
| Intended parent age (y), mean (SD) | 41.8(7.6) | 41.6 (5.4) | .0565 |
| Intended parent age (y), n (%) | |||
| <35 | 399 (20.7) | 2,530(13.8) | |
| 36–40 | 398 (20.7) | 3,848 (21.0) | |
| 41–45 | 525 (27.2) | 8,094 (44.2) | |
| 46–50 | 375 (19.5) | 3,354(18.3) | |
| 51–55 | 165 (8.6) | 442 (2.4) | |
| >55 | 65 (3.4) | 49 (0.3) | |
| Carrier age (y), mean (SD) | 31.6 (5.1) | NA | NA |
| Carrier age (y), n (%) | |||
| <35 | 1,466(78.3) | ||
| 36–40 | 325 (17.4) | ||
| 41 –45 | 69(3.7) | ||
| 46–50 | 11 (0.6) | ||
| >50 | 2(0.1) | ||
| Donor age (y), mean (SD) | 26.0 (3.4) | 26.3 (3.6) | .0984 |
| Race/ethnicity, n (%) | < .0001 | ||
| Non-Hispanic white | 680 (35.3) | 7,331 (40.0) | |
| Non-Hispanic black | 63 (3.3) | 861 (4.7) | |
| Asian | 228(11.8) | 1,998(10.9) | |
| Hispanic | 79(4.1) | 862 (4.7) | |
| Other | 6(0.3) | 55 (0.3) | |
| Missing/unknown | 871 (45.2) | 7,210(39.4) | |
| BMI of intended parent, mean (SD) | 25.0 (5.3) | 25.6 (5.6) | .0008 |
| Smoking status of intended parent, n (%) | < .0001 | ||
| Smoker | 36(1.9) | 478 (2.6) | |
| Nonsmoker | 1,703 (88.4) | 15,156(82.7) | |
| Unknown | 188 (9.8) | 2,683 (14.7) | |
| Prior gravidity of intended parent, mean (SD) | 1.4(1.8) | 1.6 (1.7) | < .0001 |
| Prior full-term birth of intended parent, mean (SD) | 0.9 (1.1) | 0.7 (1.0) | < .0001 |
| Prior preterm birth of intended parent, mean (SD) | 0.1 (0.4) | 0.1 (0.3) | .8566 |
| Prior spontaneous abortion of intended parent, mean (SD) | 1.1 (1.6) | 1.1 (1.3) | .7784 |
| Number of prior ART cycles of intended parent, mean (SD) | 2.2 (2.7) | 2.4 (3.0) | .0049 |
| Infertility diagnosis, n (%) | |||
| Male factor | 162 (8.4) | 2,962 (16.2) | < .0001 |
| Tubal factor | 49 (2.5) | 1,198(6.5) | < .0001 |
| Endometriosis | 69(3.6) | 959 (5.2) | .0016 |
| Uterine factor | 340(17.6) | 1,046(5.7) | < .0001 |
| Polycystic Ovarian syndrome | 21 (1.1) | 628 (3.4) | < .0001 |
| Diminished ovarian reserve | 887 (46.0) | 14,435 (78.8) | < .0001 |
| Unexplained | 49 (2.5) | 647 (3.5) | .0234 |
| Other | 1,002 (52.0) | 3,413 (18.6) | < .0001 |
| ART factors used, n (%) | |||
| Assisted hatching | 951 (49.4) | 8,215(44.9) | .0002 |
| ICSI | 685 (35.6) | 8,914(48.7) | < .0001 |
| PGS | 597 (31.0) | 2,204(12.0) | < .0001 |
| Number of embryos transferred, mean (SD) | 1.5 (0.7) | 1.4(0.7) | < .0001 |
| Elective single embryo transfer (eSET), n (%) | 578 (74.4) | 5,726 (78.5) | .0106 |
Note: Donor cycles types include fresh and frozen embryo transfers. ART= assisted reproductive technology; BMI = body mass index; eSET = elective single transfer, ICSI = intracyoplasmic sperm injection; PGS = preimplanation genetic screening; SD = standard deviation; NA = not applicable.
Segal. How much does the uterus matter?. Fertil Steril 2018.
Among cycles using a gestational carrier, there were 1,009 deliveries, with 716 singletons and 293 sets of multiples. Among intended parent recipients, there were 7,374 deliveries, of which 5,634 were singletons and 1,740 were multiples (Table 2). Overall, pregnancy outcomes were significantly better for cycles using a gestational carrier compared to intended parent recipients (Table 2). Patients using a gestational carrier had significantly higher odds of clinical pregnancy (adjusted OR [aOR]1.33, 95% CI 1.17–1.51) and live birth (aOR 1.37, 95% CI 1.21–1.55), compared to intended parent recipients. The miscarriage rate was higher for intended parent recipients but not statistically significant. There were significantly more multiples among the gestational carrier cycles compared to the intended parent recipients (aOR 1.32, 95% CI 1.07–1.62). Live birth rates were consistently lower for intended parent recipients compared to gestational carriers and begin to sharply decline after age 45 (Fig. 1).
TABLE 2.
Reproductive and perinatal outcomes of gestational carrier and intended parent recipient cycles using fresh and frozen donor oocytes.
| Variable | Gestational carrier (N=1,768) | Intended parent recipient (N=15,897) | OR (95% CI) | OR (95% CI)a |
|---|---|---|---|---|
| CP, n (%) | 1,153 (65.2) | 8,949 (56.3) | 1.46 (1.35, 1.62)* | 1.33 (1.17, 1.51)* |
| LB, n (%) | 1,009 (57.1) | 7,375 (46.4) | 1.54 (1.38, 1.70)* | 1.37 (1.21, 1.55)* |
| Miscarriage rate, n (%) | 136 (7.7) | 1,481 (9.3) | 0.81 (0.67, 0.98)* | 0.87 (0.71, 1.07) |
| Pregnancy Plurality, n (%)b | ||||
| Singleton | 716 (71.0) | 5,634 (76.4) | 0.76 (0.65, 0.87)* | 0.76 (0.62, 0.93)* |
| Multiple | 293 (29.0) | 1,740 (23.6) | 1.33 (1.15, 1.53)* | 1.32 (1.07, 1.62)* |
| Gestational wk, n (%)c | N=716 | N=5,632 | ||
| Full term | 591 (82.5) | 4,202 (74.6) | Reference | Reference |
| Overall PTD (<37 wk) | 125 (17.5) | 1,430 (25.4) | 0.62 (0.51, 0.76)* | 0.78 (0.61, 0.99)* |
| Late PTD (32 – 37 wk) | 103 (14.4) | 1,254 (22.3) | 0.58 (0.47, 0.73)* | 0.77 (0.59, 0.99)* |
| Very early PTD (<32 wk) | 22 (3.1) | 176 (3.1) | 0.89 (0.57, 1.40) | 0.83 (0.47, 1.46) |
| Birthweight, n (%)c | N=708 | N=5,557 | ||
| Normal birthweight | 663 (93.6) | 4,884 (87.9) | Reference | Reference |
| Overall LBW (<2500 g) | 45 (6.4) | 673 (12.1) | 0.49 (0.36, 0.67)* | 0.62 (0.44, 0.89)* |
| Term LBW ( ≥ 37 wk, <2500 g) | 7 (1.0) | 104 (1.9) | 0.47 (0.22, 1.02) | 0.88 (0.34, 2.23) |
| Preterm LBW (<37 wk, <2500 g) | 38 (5.4) | 569 (10.2) | 0.65 (0.44, 0.97)* | 0.63 (0.39, 1.00)* |
Note: aOR = adjusted odds ratio; CI = confidence interval; CP = clinical pregnancy; LB = live births; LBW = low birth weight; OR = odds ratio; PTD = preterm delivery.
Model adjusted for age, use of assisted hatching, intracytoplasmic sperm injection, preimplantation genetic diagnosis, fresh or frozen donor oocyte, and number of embryos transferred, reduction in fetal heart.
Limited to deliveries with live birth data.
Limited to singleton deliveries with live birth data, term and preterm LBW combined for analysis.
P< .05.
Segal. How much does the uterus matter?. Fertil Steril 2018.
FIGURE 1.
Rates of live birth in pregnancies conceived with donor oocytes transferred to gestational carriers (green) and intended parent recipients (red). Live-birth rates were consistently lower for intended parent recipients compared to gestational carriers.
Among singleton deliveries, the incidence of prematurity (<37 weeks) was significantly lower in gestational carriers compared to intended parent recipients (aOR 0.78, 95% CI 0.61–0.99). Prematurity from 32 to 37 weeks was also reduced in gestational carrier cycles (aOR 0.77, 95% CI 0.59–0.99). Very preterm delivery (<32 weeks) had a similar incidence of 3.1% in both groups, which may be due to a small sample size of 22 cases in the gestational carriers and 176 in the intended parent recipients. The overall trends of low birthweight and preterm delivery are illustrated in Figure 2. Intended parent recipients have a consistently higher percentage of low birthweight infants compared to gestational carriers, and that percentage starts to rise after age 43 (Fig. 2A). Similarly, preterm delivery rate starts to gradually rise after age 44 among intended parents (Fig. 2B). The odds of overall low birthweight among singletons was significantly reduced in gestational carrier cycles (aOR 0.62, 95% CI 0.44–0.89), relative to intended parent recipients (Table 2). Low birthweight at term (1.0% vs. 1.9%) and among preterm neonates (5.4% vs. 10.2%) were also reduced in gestational carrier cycles. Neonatal outcomes were similar in fresh and frozen embryo transfer cycles (Table 2).
FIGURE 2.
Rates of (A) low birthweight and (B) preterm delivery for pregnancies conceived with donor oocytes transferred to gestational carriers (green) and intended parent recipients (red). (A) Intended parent recipients have a consistently higher percentage of low birthweight infants compared to gestational carriers. (B) Similarly, preterm delivery rates start to markedly rise to a peak of 43.1% among intended parents over age 50 years.
A sub-analysis was performed to compare pregnancy outcomes of 3,858 intended parent recipients with at least one prior full-term birth and at least one prior ART cycle to 1,768 gestational carriers (Supplemental Table 1). The mean age of parous intended parent recipients and gestational carriers were 42.2 and 31.6, respectively. Clinical pregnancy and live birth were significantly higher in gestational carriers than in parous intended parent recipients with a history of prior ART (Supplemental Table 1), whereas the miscarriage rate was lower in gestational carriers than parous intended parent recipients (aOR 0.74, 95% CI 0.55–0.99). No significant associations were observed for birth outcomes. In the sub analysis of parous intended parent recipients without a history of prior ART, the pregnancy and birth outcomes were like gestational carriers (Supplemental Table 2).
DISCUSSION
This is the first study to directly compare the risks of low birthweight and preterm delivery among pregnancies conceived using donor oocytes in gestational carriers and intended parent recipients. We found that gestational carriers had higher odds of live birth after transfer of donor oocyte embryos compared to women using their own uterus. The odds of having a preterm delivery or low birthweight neonate were lower in gestational carriers compared to intended parent recipients. Finally, in our sub-group analysis, we found that gestational carrier cycles demonstrated better reproductive outcomes compared to parous intended parent recipients with a history of prior ART, though no such differences were found for intended parents without a history of ART suggesting that a history of infertility may be a contributing factor in reproductive outcomes. In addition, we found similar neonatal outcomes among parous intended parent recipients with or without prior ART compared to gestational carriers. We have also demonstrated that increasing age of the intended parent is associated with lower rates of live birth and poorer neonatal outcomes (Figs. 1 and 2).
The mechanisms behind the associations between uterine age and adverse perinatal outcomes are still largely unknown. A recent study in mice looking at the effect of uterine age on embryo development suggests that abnormal placentation and decidualization in an older uterine environment is the cause of these negative outcomes (19). A mouse model was used to differentiate the effect of age on the oocyte and the uterus and found that uterine aging itself was associated with intrauterine growth restriction (IUGR) and congenital anomalies. Using RNA-seq on placentas at mid-gestation, they found key regulators of decidual differentiation (Bmp2 and Igf1) and uterine immune cells were abnormally regulated with older age. In addition, the uterine stroma of older mice was refractory to implantation due to lower expression of progesterone and estrogen receptors in the endometrium and reduced proliferation. Even in the setting of normal embryos, neonatal low birthweight may be due to abnormal placentation resulting from abnormal decidual response to pregnancy (20).
Several studies have shown that parity is an independent predictor of uterine blood flow during a subsequent pregnancy, suggesting some permanent modifications on uterine vasculature (21–23). The validated SART live birth calculator also found that a prior history of a live birth improves subsequent ART success (24). However, even after controlling for parity in our subgroup analysis, clinical pregnancy and live birth rates were significantly higher in gestational carriers compared to parous intended parent recipients with a history of prior infertility treatment. It is interesting to note that the neonatal outcomes were similar in parous intended parent recipients regardless of a history of previous ART. This may have to do with a lower risk of preeclampsia and other disorders of placentation in parous compared to nulliparous women (25).
Strengths of our study include the large number of ART pregnancies from the most recent complete SART database in 2014. Unlike previous years, the new 2014 SART data is organized by retrieval initiated and includes use of eSET, PGD, and subsequent frozen embryo transfers, which is a more accurate representation of total cycle success. Our study included over 1,000 gestational carriers under 35 years old and 3,845 intended parent recipients over 45 years old. By restricting the analysis to donor oocyte embryos, we were able to have similar uterine preparations whether having a fresh or frozen transfer and oocyte quality across groups; this allowed us to isolate the effect of infertility on pregnancy outcomes, which is a key strength of our study. Limitations of our study include the lack of data available on gestational carriers other than age. For example, body mass index, smoking status, and prior obstetrics history would be important confounding factors that are not reported to SART. Among the intended parents’ recipients using their own uterus, 2.6% were smokers, 5.2% had endometriosis, 3.4% had PCOS and 6.5% had tubal disease. We could not control for these confounders in our models and it is possible some may be contributing to the adverse outcomes observed in the intended parent recipients. Smoking has been linked to an increased risk in preterm delivery and low birth weight (26). In addition, SART does not collect information on pregnancy complications such as preeclampsia, or other maternal complications including cardiac or cerebral venous events, maternal death, or embolic events. There is no data collected on protocols used for preparation of the endometrium for embryo transfer, whether it was a natural or medicated cycle, or the type of luteal support utilized. We had a small sample size in the very advanced maternal age category with 491 intended parent recipients and 2 gestational carriers over 50 years old. Additionally, the increased use of PGD/PGS in gestational carrier cycles may influence pregnancy outcomes but should not have affected the outcomes of preterm delivery or low birth-weight.
A major barrier to utilizing a gestational carrier is cost. Future studies analyzing the cost-effectiveness of gestational carrier cycles in older intended parent recipients would be helpful, particularly if they considered the cost of extended hospital stays due to complications from maternal, perinatal, and neonatal morbidities in older mothers. Postnatal lifetime expenses should also be considered as IUGR and low birthweight have been linked to a higher risk of chronic adult diseases (27).
The trend of older women carrying pregnancies is likely to grow in the future, as more women freeze their eggs and may serve as their own “egg donor” later in their reproductive years. Future studies should expand on this study by using several years of data to increase the sample size and focus on pregnancy outcomes of women in their fifth and sixth decades receiving donor and autologous oocytes. More animal and human research studies are needed to explore the molecular mechanisms underlying the effect of infertility on adverse perinatal outcomes. Finally, counseling patients on the potential effects of age on pregnancy outcomes, and emphasizing the importance of eSET in this context, is vital for ensuring the safest outcomes for older fertility patients.
Supplementary Material
Acknowledgments
Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Footnotes
T.R.S. has nothing to disclose. K.K. has nothing to disclose. S.L.M. has nothing to disclose. J.M.G. has nothing to disclose. R.S.W. has nothing to disclose.
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REFERENCES
- 1.Qin JB, Sheng XQ, Wu D, Gao SY, You YP, Yang TB, et al. Worldwide prevalence of adverse pregnancy outcomes among singleton pregnancies after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Arch Gynecol Obstet 2017;295:285–301. [DOI] [PubMed] [Google Scholar]
- 2.Seggers J, Pontesilli M, Ravelli AC, Painter RC, Hadders-Algra M, Heineman MJ, et al. Effects of in vitro fertilization and maternal characteristics on perinatal outcomes: a population-based study using siblings. Fertil Steril 2016;105:590–8.e2. [DOI] [PubMed] [Google Scholar]
- 3.Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Soderstrom-Anttila V, et al. Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis. Hum Reprod Update 2013;19:87–104. [DOI] [PubMed] [Google Scholar]
- 4.Paulson RJ, Boostanfar R, Saadat P, Mor E, Tourgeman DE, Slater CC, et al. Pregnancy in the sixth decade of life: obstetric outcomes in women of advanced reproductive age. JAMA 2002;288:2320–3. [DOI] [PubMed] [Google Scholar]
- 5.Abdalla HI, Wren ME, Thomas A, Korea L. Age of the uterus does not affect pregnancy or implantation rates; a study of egg donation in women of different ages sharing oocytes from the same donor. Hum Reprod 1997; 12:827–9. [DOI] [PubMed] [Google Scholar]
- 6.Check JH, Jamison T, Check D, Choe JK, Brasile D, Cohen R. Live delivery and implantation rates of donor oocyte recipients in their late forties are similar to younger recipients. J Reprod Med 2011;56:149–52. [PubMed] [Google Scholar]
- 7.Krieg SA, Henne MB, Westphal LM. Obstetric outcomes in donor oocyte pregnancies compared with advanced maternal age in in vitro fertilization pregnancies. Fertil Steril 2008;90:65–70. [DOI] [PubMed] [Google Scholar]
- 8.Elenis E, Sydsjö G, Skalkidou A, Lampic C, Svanberg AS. Neonatal outcomes in pregnancies resulting from oocyte donation: a cohort study in Sweden. BMC Pediatr 2016;16:170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Le Ray C, Scherier S, Anselem O, Marszalek A, Tsatsaris V, Cabrol D, et al. Association between oocyte donation and maternal and perinatal outcomes in women aged 43 years or older. Hum Reprod 2012;27:896–901. [DOI] [PubMed] [Google Scholar]
- 10.Elenis E, Svanberg AS, Lampic C, Skalkidou A, Åkerud H, Sydsjö G. Adverse obstetric outcomes in pregnancies resulting from oocyte donation: a retrospective cohort case study in Sweden. BMC Pregnancy Childbirth 2015;15: 247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Kort DH, Gosselin J, Choi JM, Thornton MH, Cleary-Goldman J, Sauer MV. Pregnancy after age 50: defining risks for mother and child. Am J Perinatol 2012;29:245–50. [DOI] [PubMed] [Google Scholar]
- 12.Dude AM, Yeh JS, Muasher SJ. Donor oocytes are associated with preterm birth when compared to fresh autologous in vitro fertilization cycles in singleton pregnancies. Fertil Steril 2016;106:660–5. [DOI] [PubMed] [Google Scholar]
- 13.Malchau SS, Loft A, Larsen EC, Aaris Henningsen AK, Rasmussen S, Andersen AN, et al. Perinatal outcomes in 375 children born after oocyte donation: a Danish national cohort study. Fertil Steril 2013;99: 1637–43. [DOI] [PubMed] [Google Scholar]
- 14.Kamath MS, Antonisamy B, Mascarenhas M, Sunkara SK. High-risk of preterm birth and low birth weight after oocyte donation IVF: analysis of 133,785 live births. Reprod Biomed Online 2017;35:318–24. [DOI] [PubMed] [Google Scholar]
- 15.Ethics Committee of the American Society for Reproductive Medicine. Oocyte or embryo donation to women of advanced reproductive age: an Ethics Committee opinion. Fertil Steril 2016;106:e3–7. [DOI] [PubMed] [Google Scholar]
- 16.Centers for Disease Control and Prevention. National summary report: 2014 ART report-division of reproductive health. Available at: https://www.cdc.gov/art/pdf/2014-report/art-2014-national-summary-report.pdf. Accessed September 9, 2017.
- 17.Paulson RJ, Thornton MH, Francis MM, Salvador HS. Successful pregnancy in a 63-year-old woman. Fertil Steril 1997;67:949–51. [DOI] [PubMed] [Google Scholar]
- 18.Society for Assisted Reproductive Technology. Number of Clinics, Treatments & Births. Available at https://www.sart.org/patients/history-of-ivf. Accessed January 1, 2018.
- 19.American Society for Reproductive Medicine. Recommendations for practices utilizing gestational carriers: a committee opinion. Fertil Steril 2017; 107:e3–10. [DOI] [PubMed] [Google Scholar]
- 20.Woods L, Perez-Garcia V, Kieckbusch J, Wang X, DeMayo F, Colucci F, et al. Decidualisation and placentation defects are a major cause of age-related reproductive decline. Nat Commun 2017;8:352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Prefumo F, Bhide A, Sairam S, Penna L, Hollis B, Thilaganathan B. Effect of parity on second-trimester uterine artery Doppler flow velocity and waveforms. Ultrasound Obstet Gynecol 2004;23:46–9. [DOI] [PubMed] [Google Scholar]
- 22.Suzuki S Influence of parity on second-trimester uterine artery Doppler waveforms in twin pregnancy. J Matern Fetal Neonatal Med 2006;19: 193–4. [DOI] [PubMed] [Google Scholar]
- 23.Hafner E, Schuchter K, Metzenbauer M, Philipp K. Uterine artery Doppler perfusion in the first and second pregnancies. Ultrasound Obstet Gynecol 2000;16:625–9. [DOI] [PubMed] [Google Scholar]
- 24.Luke B, Brown MB, Wantman E, Stern JE, Baker VL, Widra E, et al. A prediction model for live birth and multiple births within the first three cycles of assisted reproductive technology. Fertil Steril 2014; 102:744–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010;376:631–44. [DOI] [PubMed] [Google Scholar]
- 26.Mei-Dan E, Walfisch A, Weisz B, Hallak M, Brown R, Shrim A. The unborn smoker: association between smoking during pregnancy and adverse perinatal outcomes. J Perinat Med 2015;43:553–8. [DOI] [PubMed] [Google Scholar]
- 27.Barker DJ. The origins of the developmental origins theory. J Intern Med 2007;261:412–7. [DOI] [PubMed] [Google Scholar]
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