Increased incidence of preeclampsia in women conceiving by intrauterine insemination with donor versus partner sperm for treatment of primary infertility

doi:10.1016/S0002-9378(97)70215-1

American Journal of Obstetrics and Gynecology

Volume 177, Issue 2, August 1997, Pages 455-458

https://doi.org/10.1016/S0002-9378(97)70215-1 Get rights and content

Abstract

Objective: Reports suggest that there is an increased incidence of preeclampsia after a previously normal pregnancy if there is a change in paternity. We hypothesize that there is a higher incidence of preeclampsia (proteinuric hypertension) in women conceiving by intrauterine insemination with donor sperm versus intrauterine insemination with partner sperm. Study design: This was a retrospective cohort study. In women with primary infertility all pregnancies achieved by either partner or donor intrauterine insemination carried to birth of a fetus (> 20 weeks) were identified. The medical records were examined for the maternal and pregnancy outcome data. The relative risk and 95% confidence interval were calculated for the risk of preeclampsia. The baseline data were compared with t tests, χ² analysis and Fisher's exact test where appropriate. Results: Forty-four patients in the partner intrauterine insemination group and 37 in the donor insemination group were identified as having primary infertility. Three cases of mild preeclampsia were found in the partner insemination program and nine cases of preeclampsia (five severe, four mild) in the donor insemination program (relative risk 1.85, 95% confidence interval 1.20 to 2.85). Conclusions: There is a higher incidence of preeclampsia in women conceiving by intrauterine insemination with washed donor sperm compared with intrauterine insemination with washed partner sperm. This supports, indirectly, an immunologic basis for preeclampsia. The antigenic factor would appear to be located on the sperm as opposed to the seminal fluid itself. (Am J Obstet Gynecol 1997;177:455-8.)

Section snippets

Methods

This was a retrospective cohort study. All pregnancies achieved by either intrauterine insemination with the partner's washed sperm or by intrauterine insemination with washed donor sperm, and giving birth to a fetus after 20 weeks' gestation, were identified. To rule out confounding variables that may increase or decrease the risk of preeclampsia, only women with primary infertility and no known medical disorders were included. Primary infertility was defined as no previous pregnancy and the

Results

There were 78 pregnancies carried to >20 weeks in the intrauterine insemination with partner's sperm program. Data were available on 72 of these patients, 44 of whom met the inclusion criteria of primary infertility and no identified medical disorders. Of the six patients for whom pregnancy outcome data were not available, two patients were being treated for primary infertility. In the donor insemination program, 59 pregnancies were carried to >20 weeks of gestation. Data were available on 57

Comment

It has long been suggested that the etiology of preeclampsia-eclampsia has an immunologic component. It was postulated that this disorder represented either a disruption of the normal mechanism(s) responsible for the protection of the fetoplacental unit from rejection as an allograft or an aberrant immunologic response directed against tissue- or organ-specific antigens associated with the placenta.⁷

Prolonged exposure of women to their partners' semen (semen “inoculations”) before conceiving

Acknowledgements

We thank Janice P. Van Dijk for editing, Carolyn Ferguson and June Trueman for their assistance, and Dr. Robert L. Reid for his interest in this work.

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Higher incidence of preeclampsia among participants undergoing in-vitro fertilization after fewer sperm exposures
2023, European Journal of Obstetrics and Gynecology and Reproductive Biology
Evaluation of preeclampsia (PE) incidence among participants undergoing in vitro fertilization (IVF) after various cycles of sperm donation (SD) via intrauterine inseminations (IUI) or IVF.
A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019 which included participants who conceived via IVF using SD from a single sperm bank and had a successful singleton birth at Sheba Medical Center. The study cohort was divided into two groups: Group 1 (participants who conceived via IVF after 0–1 cycles of IUI or IVF from the same sperm donor) and Group 2 (participants who conceived via IVF after 2 or more cycles of IUI or IVF from the same sperm donor).
Baseline characteristics and pregnancy outcomes between the two groups were compared. In addition, a comparison between the study groups and a control of participants of the same age who conceived spontaneously and had a singleton birth at Sheba Medical Center during the same period with a record of up to two previous deliveries was done.
A total of 228 participants conceived through IVF from SD and met the inclusion criteria. Of these, 110 were defined as Group 1 and 118 as Group 2. The participants showed no differences in their age, gravidity and parity, chronic medical conditions, or history of pregnancy complications.
Preeclampsia was positively associated with Group 1 (9 [8.2%] vs. 2 [1.7%], P = 0.022).
PE was observed to be more prevalent in Group 1 (P < 0.001) when compared to a control group of 45,278 participants who conceived spontaneously. No significant differences were observed in comparing Group 2 with the same control group.
The incidence of PE was higher among participants who were exposed to 0–1 IUI or IVF cycles than in those who were exposed to 2 or more cycles of IUI or IVF from the same sperm donor. On comparing both groups with a control group, the incidence of PE was higher in participants who were exposed to 0–1 cycles, while there was no difference in participants exposed to 2 or more cycles.
If there is a statistically significant increase in the incidence of PE when conception occurred following fewer sperm exposures, then there may be a correlation between these two. The reason for this is not entirely clear, but based on former literature, we hypothesize it may be related to the fact that repeated exposures to paternal antigens may alter the maternal immune response causing a better adaptation to the semi-allogenic nature of the fetus, its paternal half.
Donated-embryo pregnancies are associated with increased risk of hypertensive disorders even for young recipients: a retrospective matched-cohort study
2023, Fertility and Sterility
To determine whether pregnancies with donated embryos are at a higher risk of complications than the pregnancies from autologous frozen-thawed embryo transfer (FET).
Anonymous, multicenter, comparative, observational, retrospective, matched-cohort study.
Six French assisted reproductive technique centers from 2003 to 2018.
Seventy-three singleton pregnancies with donated embryos (exposed) and 136 singleton pregnancies after autologous FET (nonexposed) were matched at 7–8 weeks of gestation (pregnancy date, parity, and women’s age) (2:1 ratio, respectively). In accordance with French practices, all women were <44 years old and donated embryos were discarded frozen embryos from other couples.
Not applicable.
Percentages of hypertensive disorders of pregnancy (HDPs) with donated embryos versus autologous FET.
Groups were comparable (mean age: 34.5 years) and HDPs (24.6% vs. 11.9%) were significantly more frequent among the donated-embryo pregnancies, mostly in its severe forms (17.5% vs. 4.6%). In contrast, their respective isolated hypertension frequencies were comparable (7.0% vs. 7.3%). Multivariate analysis retained increased severe HDP risk with donated embryos (odds ratio 2.08 [95% confidence interval: 1.08–4.02]). No significant effect of endometrial preparation was observed. C-sections were more frequent for donated-embryo pregnancies (47.3% vs. 29.2%). Newborns from embryo donation or autologous FET were comparable for prematurity, birth weight and length, Apgar score, small for gestational age, large for gestational age, neonatal malformations, and sex ratio.
Even for young women, the risk of severe HDP was 4 times higher for donated-embryo pregnancies than for autologous-FET pregnancies. The HDP risk must be acknowledged to inform donated-embryo recipients and provide careful pregnancy monitoring.
un estudio de cohorte-emparejado retrospectivo.
Determinar si los embarazos con embriones donados se encuentran en mayor riesgo de complicaciones que los embarazos de transferencias autólogas de embriones congelados-descongelados (FET).
Estudio anónimo, multicéntrico, comparativo, observacional, de cohorte-emparejado retrospectivo.
Seis centros de técnicas de reproducción asistida franceses desde 2003 hasta 2018.
Setenta y tres embarazos únicos con embriones donados (expuestos) y 136 embarazos únicos luego de una FET autóloga (no expuestos) fueron emparejados en la semana 7-8 de gestación (fecha de embarazo, paridad, y edad de las mujeres) (proporción 2:1, respectivamente). De acuerdo con las prácticas francesas, todas las mujeres eran <44 años y los embriones donados fueron embriones congelados descartados de otras parejas.
No aplica.
Porcentajes de desórdenes hipertensivos en el embarazo (HDPs) con embriones donados versus FET autóloga.
Los grupos fueron comparables (edad promedio: 34.5 años) y HDPs (24.6% vs. 11.9%) fueron significativamente más frecuentes entre los embarazos de embriones donados, sobre todo en sus formas más severas (17.5% vs. 4.6%). En contraste, sus frecuencias de hipertensión aisladas fueron comparables (7.0% vs. 7.3%). Un análisis de multivariante retuvo un aumento del riesgo de HDP severo con embriones donados (relación de probabilidades 2.08 [95% intervalo de confianza: 1.08–4.02]). No se observaron efectos de preparación endometrial significantes. Las cesáreas fueron más frecuentes en embarazos de embriones donados (47.3% vs. 29.2%). Recién nacidos de embriones donados o FET autólogas fueron comparables para nacimiento prematuro, peso y longitud al nacer, puntaje de Apgar, pequeño para edad gestacional, grande para edad gestacional, malformaciones neonatales y proporción de sexos.
El riesgo de HDP severo es 4 veces más alto para embarazos de embriones donados que para embarazos de FET autólogas incluso para mujeres jóvenes. El riesgo de HDP debe ser reconocido para informar a las receptoras de embriones donados y proporcionar un monitoreo cuidadoso del embarazo.
Preeclampsia risk in oocyte donation versus double gamete donation pregnancies: A systematic review and meta-analysis
2022, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
This theory is supported by several studies reporting an increased prevalence of preeclampsia in pregnancies achieved after OD [10–13]. Moreover, pregnancies achieved after sperm donation have also been associated with an increased risk of preeclampsia [14–16], as records suggest that maternal tolerance to paternal antigens begins with vaginal exposure to partner’s sperm and the risk of preeclampsia is related to the duration of this exposure [17]. As more women delay childbearing, the use of OD in assisted reproductive technology has escalated over the last decades, given that fecundity drops rapidly after the age of 35 years and the success rate of in vitro fertilization (IVF) with autologous oocytes decreases after the age of 40 [18].
The number of pregnancies achieved through gamete donation has escalated over the last decades. It has been hypothesized that double gamete donation pregnancies would have a higher risk of preeclampsia compared to single gamete donation pregnancies due to cumulative risk of preeclampsia in oocyte donation pregnancies and the separate risk associated with sperm donation. Therefore, a systematic review and meta-analysis was conducted to explore the association between double gamete donation pregnancies and the development of preeclampsia and gestational hypertension, comparing it with oocyte donation alone. A systematic search of five databases was conducted and meta-analysis was performed using a random-effects model. Of 795 screened articles, five met our selection criteria for a systematic review, and four were included in the meta-analysis. No statistically significant differences were found in the risk of preeclampsia between study subgroups (odds ratio [OR] 0.82; 95% confidence interval [95%CI] 0.29–2.36), even after subgroup analysis considering only high-quality studies (OR 1.30; 95%CI 0.61–2.76; I² = 0%). Regarding gestational hypertension risk, neither the pooled analysis (OR 0.52; 95%CI 0.18–1.49; I² = 84%) nor the high-quality studies subgroup analysis (OR 0.67; 95%CI 0.33–1.35; I² = 0%) find any significant differences between oocyte donation or double gamete donation pregnancies. There appears to be little difference in gestational hypertension or preeclampsia risk between pregnancies resulting from double gamete donation and those from oocyte donation alone. Strict obstetrical surveillance should be considered standard of care for these women, in an attempt to perform early diagnosis and management of hypertensive disorders.
Obstetric and perinatal risks after the use of donor sperm: A systematic review and meta-analysis
2022, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
In vitro fertilization (IVF) using donor sperm (IVF-D) is a treatment option for couples with male factor infertility when IUI-D treatment fails, or when there is a female factor present, e.g. a tubal factor, severe endometriosis, or increased age of the woman. Over the years, increasing evidence of a higher risk of preeclampsia (PE) in pregnancies after use of donor sperm has arisen [11–14]. Hypertensive disorders of pregnancy (HDP) and PE are not only associated with adverse maternal and fetal short-term outcomes [15] but also with increased morbidity and mortality in later life of the mother [16] and the child [17].
Donor sperm is widely used in infertility treatments. The purpose of the study was to investigate, whether use of donor sperm in intrauterine insemination (IUI) or in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments affect maternal and perinatal risks compared with spontaneously conceived pregnancies or use of partner sperm in IUI, IVF or ICSI. We provide a systematic review and meta-analyses on the most clinically relevant obstetric and perinatal outcomes after use of donor sperm compared with partner sperm: hypertensive disorders of pregnancy, preeclampsia, low birth weight, and preterm birth. Our meta-analyses showed an increased risk for preeclampsia (pooled adjusted odds ratio (aOR) 1.77, 95% CI 1.26–2.48) and hypertensive disorders of pregnancy (pooled aOR 1.55, 95%, CI 1.20–2.00) in pregnancies resulting from IUI with donor sperm compared with IUI with partner sperm. No increased risk was seen for low birth weight or preterm birth after the use of donor sperm in IUI compared with the use of partner sperm in IUI. Subgroup analysis for singletons only did not change these results. The meta-analysis on low birth weight showed a lower risk after in IVF with donor sperm compared with IVF with partner sperm (pooled aOR 0.89, 95% CI 0.83–0.94). For hypertensive disorders of pregnancy, preeclampsia and preterm birth, no difference was found between IVF with donor sperm vs. partner sperm. Patients need to be informed about the moderately increased risk of hypertensive disorders of pregnancy and preeclampsia in pregnancies after IUI with donor sperm.
The placenta and preeclampsia: villain or victim?
2022, American Journal of Obstetrics and Gynecology
Preeclampsia is a disease whose characterization has not changed in the 150 years since the cluster of signs associated with the disorder were first described. Although our understanding of the pathophysiology of preeclampsia has advanced considerably since then, there is still little consensus regarding the true etiology of preeclampsia. As a consequence, preeclampsia has earned the moniker “disease of theories,” predominantly because the underlying biological mechanisms linking clinical epidemiologic findings to observed organ dysfunction in preeclampsia are far from clear. Despite the lack of cohesive evidence, expert consensus favors the hypothesis that preeclampsia is a primary placental disorder. However, there is now emerging evidence that suboptimal maternal cardiovascular performance resulting in uteroplacental hypoperfusion is more likely to be the cause of secondary placental dysfunction in preeclampsia. Preeclampsia and cardiovascular disease share the same risk factors, preexisting cardiovascular disease is the strongest risk factor (chronic hypertension, congenital heart disease) for developing preeclampsia, and there are now abundant data from maternal echocardiography and angiogenic marker studies that cardiovascular dysfunction precedes the development of preeclampsia by several weeks or months. Importantly, cardiovascular signs and symptoms (hypertension, cerebral edema, cardiac dysfunction) predominate in preeclampsia at clinical presentation and persist into the postnatal period with a 30% risk of chronic hypertension in the decade after birth. Placental malperfusion caused by suboptimal maternal cardiovascular performance may lead to preeclampsia, thereby explaining the preponderance of cardiovascular drugs (aspirin, calcium, statins, metformin, and antihypertensives) in preeclampsia prevention strategies. Despite the seriousness of the maternal and fetal consequences, we are still developing sensitive screening, reliable diagnostic, effective therapeutic, or improvement strategies for postpartum maternal cardiovascular legacy in preeclampsia. The latter will only become clear with an acceptance and understanding of the cardiovascular etiology of preeclampsia.
Risk of preeclampsia in pregnancies resulting from double gamete donation and from oocyte donation alone
2018, Pregnancy Hypertension
Citation Excerpt :
Despite pre-eclampsia (PE) complicates between 2 and 7% of all gestations [1–3], its still unknown etiology can be explained by two different theories: the vascular theory suggests that oxidative stress and other related factors cause endothelial damage and impaired trophoblast invasion of the myometrial arteries, which in turn leads to disrupted placentation [4].
Pregnancies after gamete donation are at higher risk of developing pre-eclampsia (PE) than those achieved by IVF with patient’s own gametes. We aim to assess whether pregnancies achieved with both oocyte and sperm donation (double donation, DD) are at an increased risk of developing PE and gestational hypertension (GH) compared to those achieved by oocyte donation alone (OD).
Retrospective cohort study of 433 patients who reached the 20th week of gestation with either DD (n = 81) or OD (n = 352) between March 2013 and April 2016 at a fertility clinic. The risk of preterm PE, term PE, and gestational hypertension (GH) are presented as unadjusted and adjusted odds ratio (OR).
DD have a higher risk of preterm PE than OD, with an OR of 3.02 (95%CI 1.11–8.24; p = 0.031). We found no difference in the risk of term PE (OR 0.26, 95%CI 0.03–1.98; p = 0.19) or of GH (OR 1.23, 95% CI 0.63–2.43; p = 0.55).
Pregnancies with DD are at higher risk of developing preterm PE than OD alone. Patients, and physicians treating them, should be made aware of the elevated risk of PE in these gestations, in order to start prophylactic measures during the first weeks of pregnancy.

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^☆: From the Departments of Obstetrics and Gynaecology, Queen's University^a and University of Ottawa.^b

^☆☆: Reprint requests: Graeme N. Smith, MD, PhD, Department of Obstetrics and Gynaecology, Queen's University, Kingston General Hospital, 76 Stuart St., Kingston, Ontario, Canada K7L 2V7.

^★: 6/1/82251

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Increased incidence of preeclampsia in women conceiving by intrauterine insemination with donor versus partner sperm for treatment of primary infertility☆,☆☆,★

Abstract

Section snippets

Methods

Results

Comment

Acknowledgements

Eur J Obstet Gynecol Reprod Biol

J Reprod Immunol

Am J Obstet Gynecol

Lancet

Lancet

J Reprod Immunol

Lancet

Lancet

Baillieres Clin Obstet Gynaecol

Eur J Obstet Gynecol Reprod Biol

Pregnancy related hypertension