Birth Outcomes Following Assisted Reproductive Technology Conception Among Same-Sex Lesbian Couples vs Natural Conception and Assisted Reproductive Technology Conception Among Heterosexual Couples

Abstract

This study uses registry data to compare birth outcomes, including birth weight, gestational age, low birth weight, and preterm delivery, in assisted reproductive technology (ART) pregnancies among same-sex lesbian couples vs natural conceptions and ART pregnancies among heterosexual couples.

Higher rates of adverse birth outcomes have been consistently reported among children conceived via assisted reproductive technology (ART) compared with children conceived through natural conception.¹ Higher rates of multiple births in ART pregnancies partially explain the increased risk.^2,3 It remains unclear to what extent the remaining difference can be attributed to the reproductive technology or to factors related to infertility, which is associated with an elevated risk of poorer birth outcomes.^4,5 Same-sex lesbian couples undergo ART treatments generally without experiencing infertility. To distinguish the effects of reproductive treatment and infertility, we compared birth outcomes in ART pregnancies among same-sex lesbian couples vs natural conceptions and ART pregnancies among heterosexual couples.

Methods

In Sweden, same-sex lesbian couples have been eligible to receive publicly funded ART treatments with donated sperm since 2005. This study included all births in Sweden from 2007 to 2018. Using pseudonymized personal identifiers, the Swedish National Quality Registry for Assisted Reproduction, which includes all ART treatments (in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI], and intrauterine insemination [IUI]), was linked to the medical birth register and the total population registers, which include information on birth outcomes and sociodemographic characteristics. We focused on first live births for ART and naturally conceived births because 97.3% of ART births among same-sex lesbian couples were first births. We analyzed 4 outcomes: birth weight (continuous), gestational age (continuous), low birth weight (binary, <2500 g), and preterm delivery (binary, <37 weeks of gestation). We estimated linear models on the continuous outcomes and linear probability models on the binary outcomes comparing ART-conceived births among same-sex lesbian couples (reference category) with ART births and naturally conceived births among heterosexual couples. For each outcome, we estimated unadjusted and adjusted (controlling for child sex, multiplicity, and maternal age at birth) models. We also estimated differences focusing on children conceived via IVF/ICSI because 99.4% of ART births among heterosexual couples were conceived via IVF/ICSI compared with 63.3% in same-sex couples, as same-sex couples often start treatments with IUI, which has a lower chance of success regardless of subfertility.⁶

Analyses were conducted using R version 4.1.1 (R Foundation). Statistical significance was set at P < .05 (2-sided). This study was approved by the Regional Ethical Review Board of Stockholm. Informed consent was not required for pseudonymized data.

Results

During the study period, there were 868 ART births among same-sex lesbian couples, 23 488 ART births among heterosexual couples, and 456 898 naturally conceived births. ART-conceived births from same-sex and heterosexual couples showed a higher proportion of multiplicity (5.8% and 7.5%, respectively) than naturally conceived births (2.1%) (Table 1). Couples who conceived naturally had significantly lower birth weight and gestational age and similar risk of low birth weight and preterm delivery compared with same-sex couples who conceived via ART (Table 2). For example, birth weight was 3429.5 g in naturally conceived births vs 3460.2 g in same-sex ART births (adjusted difference, −76.2 g [95% CI, −113 to −39.3 g]; P < .001; low birth weight, 4.9% vs 6.7%, adjusted difference, 0.28 [95% CI, −1.11 to 1.66] percentage points; P = .70). Heterosexual couples who conceived via ART had statistically significantly lower birth weight and gestational age than same-sex couples (eg, birth weight: 3342.9 g vs 3460.2 g; adjusted difference, −97.4 g [95% CI, −134.8 to −59.9 g]; P < .001). Percentages of low birth weight and preterm birth were higher in ART conceptions among heterosexual couples vs same-sex couples but did not reach statistical significance (eg, low birth weight: 8.9% vs 6.7%; adjusted difference, 1.23 [95% CI, −0.17 to 2.65] percentage points; P = .09). The results were qualitatively similar when only considering IVF/ICSI-conceived children (Table 2).

Table 1. Descriptive Characteristics of the Analytical Samples by Mode of Conception (First Births Between 2007 and 2018).

Characteristics	ART conception		Natural conceptions
	Same-sex lesbian couples	Heterosexual couples
No. of observations	868	23 488	456 898
Multiple births, %	5.8a	7.5b	2.1
Maternal age at birth, mean (SD), y	32.9 (4.1)a,c	33.2 (4.3)b	28.3 (5.0)
Infant sex, %
Female	50.9	48.4	48.5
Male	49.1	51.6	51.5

Abbreviation: ART, assisted reproductive technology.

^a ART births among same-sex couples were statistically different from naturally conceived births (P < .05).

^b ART-conceived births among heterosexual couples were statistically different from naturally conceived births (P < .05).

^c ART births in same-sex couples were statistically different from ART-conceived births among heterosexual couples (P < .05).

Table 2. Comparison of Birth Outcomes Between the Analytical Samples by Mode of Conception (First Births Between 2007 and 2018).

Outcomes	Absolute values, mean	Unadjusted model		Adjusted model (by child sex, maternal age, and multiple birth)		Adjusted model for IVF-/ICSI-conceived birthsa
		Mean difference (95% CI)	P value	Mean difference (95% CI)	P value	Mean difference (95% CI)	P value
Birth weight, gb
ART conception
Same-sex lesbian couples	3460.2c	[Reference]		[Reference]		[Reference]
Heterosexual couples	3342.9d	−117.3 (−156.5 to −78.1)	<.001	−97.4 (−134.8 to −59.9)	<.001	−88.2 (−135.9 to −40.4)	<.001
Natural conception	3429.5	−30.7 (−69.2 to 7.9)	.12	−76.2 (−113.0 to −39.3)	<.001	−66.9 (−114.14 to −19.6)	.006
Gestational age, db
ART conception
Same-sex lesbian couples	278.1c	[Reference]		[Reference]		[Reference]
Heterosexual couples	274.7d	−3.5 (−4.4 to −2.5)	<.001	−2.9 (−3.8 to −2.0)	<.001	−2.5 (−3.7 to −1.4)	<.001
Natural conception	277.6	−0.50 (−1.5 to 0.5)	.31	−1.3 (−2.2 to −0.4)	.004	−0.9 (−2.2 to 0.19)	.10
Low birth weight (<2500 g), %e
ART conception
Same-sex lesbian couples	6.7c,f	[Reference]		[Reference]		[Reference]
Heterosexual couples	8.9d	2.23 (0.73 to 3.72)	.004	1.23 (−0.17 to 2.65)	.09	0.86 (−0.94 to 2.66)	.35
Natural conception	4.9	−1.76 (−3.23 to −0.29)	.02	0.28 (−1.11 to 1.66)	.70	−0.1 (−1.88 to 1.68)	.91
Preterm delivery (<37 wk of gestation), %e
ART conception
Same-sex lesbian couples	9.1f	[Reference]		[Reference]		[Reference]
Heterosexual couples	11.2d	2.14 (0.40 to 3.88)	.02	1.25 (−0.42 to 2.92)	.14	0.84 (−1.29 to 2.97)	.44
Natural conception	6.9	−2.18 (−3.89 to −0.47)	.01	−0.29 (−1.94 to 1.36)	.73	−0.67 (−2.78 to 1.45)	.54

Abbreviations: ART, assisted reproductive technology; ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilization.

^a There were 527 IVF/ICSI births among same-sex lesbian couples and 23 001 among heterosexual couples.

^b Linear model.

^c ART births among same-sex couples were statistically different from ART-conceived births among heterosexual couples (P < .05).

^d ART-conceived births among heterosexual couples were statistically different from naturally conceived births (P < .05).

^e Linear probability models.

^f ART births among same-sex couples were statistically different from naturally conceived births (P < .05).

Discussion

This study demonstrated that same-sex lesbian couples undergoing ART had more favorable or similar birth outcomes to heterosexual couples who conceived naturally or underwent ART to conceive, suggesting that infertility-related factors rather than reproductive treatments contribute to higher rates of adverse birth outcomes in ART pregnancies. Limitations of the study include that the presence of infertility factors was not directly assessed and the relatively small sample size of same-sex couples reduced the statistical power of the study, particularly in the binary outcomes analyses.

Section Editors: Jody W. Zylke, MD, Deputy Editor; Kristin Walter, MD, Senior Editor.