Is the Lack of Prior Exposure to Sperm Antigens Associated With Worse Neonatal and Maternal Outcomes?

Is the Lack of Prior Exposure to Sperm Antigens Associated With Worse Neonatal and Maternal Outcomes? A 10 Years Single-center Experience Comparing ICSI-TESE Pregnancies From ICSI Pregnancies

The objective of this study is to determine if the lack of exposure to sperm antigens is associated with worse maternal and neonatal outcomes in pregnancies obtained after ICSI (intracytoplasmic sperm injection)-TESE (testicular sperm extraction) for obstructive azoospermia.

The primary outcomes that will be investigated include:

• Maternal outcomes: live birth rate (LBR), abortion rate, and the rate of the main obstetrics complication, such as pre-eclampsia, gestational hypertension and diabetes mellitus.
• Neonatal outcomes: gestational age, prematurity rate, birth weight, sex ratio, 1- and 5-min APGAR, birth defects.

Study Overview

• Status: Completed
• Conditions: Obstetric Complication; Obstructive Azoospermia

Detailed Description

Several studies investigated the role of paternal factors in the development of preeclampsia; in particular, they analyzed the correlation between the vaginal exposure to male partner's semen and the incidence of preeclampsia, observing both a reduced risk of preeclampsia after prolonged exposure to the paternal seminal fluid and a higher incidence of preeclampsia in pregnancies conceived with a new father or with sperm donor. This leads to the hypothesis of an immunological role for sperm in inducing a mucosal immune tolerance-like status at the level of the uterus that could be critical in the subsequent implantation.

Previous studies also examined the neonatal outcomes from pregnancies obtained from surgically retrieved sperm, either epididymal or testicular sperm, and underlined that there is not overall increased risk in neonatal outcomes.

Our study aims at having a complete view on paternal, maternal and neonatal information and a follow up, that allows to correct possible confounders and to analyze a wider group of outcomes.

• Study Type: Observational
• Enrollment (Actual): 400

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study database will include all the pregnancies occurred between January 2010 and December 2019 at Humanitas Fertility Center after ICSI-TESE cycles for obstructive azoospermia.

A comparison of maternal and neonatal outcomes will be performed among the above-mentioned pregnancies and pregnancies from ICSI cycles with ejaculated sperm of couples with different indications occurred in the same period of time.

The controls will be matched to the cases for the principal risk factors for adverse maternal and neonatal outcomes (maternal age, BMI) with a ratio of 1:2.

Description

Inclusion Criteria for case arm:

• primary infertility
• diagnosis of obstructive azoospermia
• ICSI-TESE cycles

Inclusion Criteria for control arm:

• primary infertility
• ICSI cycles with sperm from ejaculate

Exclusion Criteria:

• pre-gestational hypertension
• pre-gestational diabetes

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pregnancies from ICSI-TESE cycles for obstructive azoospermia.; Pregnancies occurred between January 2010 and December 2019 at Humanitas Fertility Center after ICSI-TESE cycles for obstructive azoospermia.
Pregnancies from ICSI cycles with ejaculated sperm.; Pregnancies occurred between January 2010 and December 2019 at Humanitas Fertility Center after ICSI cycles with ejaculated sperm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate (LBR)	Rate of delivery of a living baby after at least 22 weeks of gestation	10 years
Abortion Rate (AR)	Proportion of clinical pregnancies who failed to continue beyond 22 weeks of gestation	10 years
Maternal complications rate	Incidence of the obstetric complications, such as pre-eclampsia, gestational hypertension and diabetes, placenta previa and placental abruption.	10 years
Gestational age	Mean gestational age of the pregnancies considered (written with both weeks and days; eg, 39 weeks and 0 days)	10 years
Prematurity rate	Rate of pregnancies lasted less than 37 weeks and 0 days	10 years
Birth weight	Mean birth weight of the neonates, written in grams.	10 years
Sex ratio	Ratio between males and females among the newborns	10 years
1- and 5-min APGAR	Objective score of the condition of a baby after birth, at 1 and 5 minutes from the delivery (from 1 to 10 points).	10 years
Incidence of congenital defects	Incidence of congenital malformations, deformations and chromosomal abnormalities among the newborns of the study group (eg. clubfoot deformity, anorectal malformations, heart defects, ...)	10 years

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas

Publications and helpful links

General Publications

• Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril. 2016 Sep 1;106(3):511-9. doi: 10.1016/j.fertnstert.2016.07.1101. Epub 2016 Jul 30.
• Verwoerd GR, Hall DR, Grove D, Maritz JS, Odendaal HJ. Primipaternity and duration of exposure to sperm antigens as risk factors for pre-eclampsia. Int J Gynaecol Obstet. 2002 Aug;78(2):121-6. doi: 10.1016/s0020-7292(02)00130-3.
• Wang JX, Knottnerus AM, Schuit G, Norman RJ, Chan A, Dekker GA. Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia. Lancet. 2002 Feb 23;359(9307):673-4. doi: 10.1016/S0140-6736(02)07804-2.
• Di Mascio D, Saccone G, Bellussi F, Vitagliano A, Berghella V. Type of paternal sperm exposure before pregnancy and the risk of preeclampsia: A systematic review. Eur J Obstet Gynecol Reprod Biol. 2020 Aug;251:246-253. doi: 10.1016/j.ejogrb.2020.05.065. Epub 2020 Jun 1.
• Dekker G, Robillard PY, Roberts C. The etiology of preeclampsia: the role of the father. J Reprod Immunol. 2011 May;89(2):126-32. doi: 10.1016/j.jri.2010.12.010. Epub 2011 May 6.
• Andraweera P, Roberts CT, Leemaqz S, McCowan L, Myers J, Kenny LC, Walker J, Poston L, Dekker G; SCOPE Consortium. The duration of sexual relationship and its effects on adverse pregnancy outcomes. J Reprod Immunol. 2018 Aug;128:16-22. doi: 10.1016/j.jri.2018.05.007. Epub 2018 May 18.
• Klonoff-Cohen HS, Savitz DA, Cefalo RC, McCann MF. An epidemiologic study of contraception and preeclampsia. JAMA. 1989 Dec 8;262(22):3143-7.
• Robillard PY, Dekker G, Chaouat G, Hulsey TC, Saftlas A. Epidemiological studies on primipaternity and immunology in preeclampsia--a statement after twelve years of workshops. J Reprod Immunol. 2011 May;89(2):104-17. doi: 10.1016/j.jri.2011.02.003. Epub 2011 May 4.
• Jin L, Li Z, Gu L, Huang B. Neonatal outcome of children born after ICSI with epididymal or testicular sperm: A 10-year study in China. Sci Rep. 2020 Mar 20;10(1):5145. doi: 10.1038/s41598-020-62102-y.
• Belva F, De Schrijver F, Tournaye H, Liebaers I, Devroey P, Haentjens P, Bonduelle M. Neonatal outcome of 724 children born after ICSI using non-ejaculated sperm. Hum Reprod. 2011 Jul;26(7):1752-8. doi: 10.1093/humrep/der121. Epub 2011 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 20, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Neonatal outcomes
• Additional Relevant MeSH Terms: Infertility, Male; Infertility; Azoospermia
• Other Study ID Numbers: 1916

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No