Abstract
Study question
Does sperm genomic integrity affect the intrauterine insemination (IUI) outcomes in couples with unexplained infertility and young maternal age?
Summary answer
Spermatozoa with higher genomic integrity are correlated with higher clinical pregnancy rates in couples with unexplained infertility undergoing IUI.
What is known already
It is known that elevated sperm chromatin fragmentation (SCF) on the male gamete affects embryo development and implantation. This is particularly relevant in IVF as well as programmed intercourse and IUI. By complementing the standard semen analysis with an SCF assay, we can assess the competence of the male gamete and its ability to generate euploid embryos and healthy offspring. Elevated SCF has been used as a way to identify subtle male factor infertility in couples undergoing IUI with poor pregnancy outcomes in order to plan for further treatments.
Study design, size, duration
This is a retrospective cohort study of IUI outcomes of couples with young maternal age and a negative infertility workup treated at our center from 2016–2020. Terminal deoxynucleotidyl dUTP transferase nick-end labeling (TUNEL) assay was used to assess sperm genomic integrity. Couples were grouped based on SCF level: normal (≤15%) or abnormal (>15%). Rates of clinical pregnancy, defined as the presence of a fetal heartbeat, were compared between the groups following IUI.
Participants/materials, setting, methods
A total of 189 consenting couples, in which the female partner had a normal uterine cavity and patent fallopian tubes, underwent 454 IUI attempts. Only women ≤37 years old were included to control for age-related confounding factors. At least 500 spermatozoa were assessed per patient, and a threshold of ≤ 15% was considered normal. Women were either untreated for natural cycle IUI or stimulated with clomiphene citrate, gonadotropins, or Letrozole.
Main results and the role of chance
A total of 454 IUI cycles were reported at our center; 302 of these were carried out in 132 couples in which the male partner had normal SCF averaged at 9.29%. The average maternal age was 34.1±3 years, and the average paternal age was 37.1±5 years. These men had the following semen parameters: a concentration of 46.2±5x106/mL, 43.8±3% motility, and an average SCF of 9.3±3%. There were 45 documented clinical pregnancies (45/302, 14.9%) as confirmed by the presence of at least one fetal heartbeat detected by ultrasound; 26 delivered, 9 are ongoing, 5 were spontaneous abortions, and 5 were lost to follow-up. A total of 57 couples in which the male partner (37.2±5.9 years) had abnormal SCF underwent 152 IUI cycles (maternal age, 34.0±2.7 years). The men had the following semen parameters: an average SCF of 23.8±10 (p < 0.0001), a concentration of 26.0±10 x106/ml, and 40.1±4% motility. These IUI attempts yielded a clinical pregnancy rate of only 4.6% (7/152; P < 0.0001); 4 delivered and 3 were spontaneous abortions.
Limitations, reasons for caution
This study is a retrospective cohort analysis of a relatively small number of patients. Furthermore, most patients were screened for SCF due to at least one prior IUI failure. A prospective, randomized trial, in which men are concurrently screened for SCF levels at the first IUI attempt, would be ideal.
Wider implications of the findings: Assessment of SCF at the initial male infertility screening can be a useful tool to investigate the competence of the male gamete. Screening couples with idiopathic infertility for a subtle male factor would guide those with higher SCF toward alternative reproductive treatments to avoid unnecessary IUI treatments.
Trial registration number
Not applicable
Sperm Chromatin Dispersion Test before Sperm Preparation Is Predictive of Clinical Pregnancy in Cases of Unexplained Infertility Treated with Intrauterine Insemination and Induction with Clomiphene Citrate