SUMMARY: HOW LONG SHOULD MALES ABSTAIN BEFORE IUI
In this study, males who abstained for 1 day or 3 days before intrauterine insemination (IUI), had similar clinical and ongoing pregnancy rates (P>0.75), meaning males can abstain for just 1 day before IUI without negatively affecting IUI success rates.
Intrauterine insemination (IUI) is still a first-line treatment option in many clinics despite the UK National Institute for Health and Care Excellence (NICE) guidelines now recommending (In vitro fertilisation) IVF and intra-cytoplasmic Sperm Injection technology (ICSI) instead of IUI in some cases of infertility. Given IUI is less expensive, less invasive and easier to perform, health experts still believe that efforts to improve its success rate is more than warranted.
Although several factors such as a patient’s age, sperm parameters and duration of infertility have all been studied to determine if and how much these factors affect IUI success rates, one factor still divides the opinions of experts, that is sperm DNA fragmentation. The relationship between sperm DNA fragmentation and IUI pregnancy rates is still inconclusive.
Another issue that researchers are still debating, is the optimal period for ejaculatory abstinence before giving a semen sample. The 3 biggest authorities, in the field of reproductive health, that is the World Health Organisation, the American Society for Reproductive Medicine and the American Urological Association all have different recommendations, creating confusion among Doctors and patients.
For this reason studies examining the relationship between ejaculatory abstinence and DNA fragmentation in IUI cycles are still required to improve patient reproductive outcomes.
To examine the effect of ejaculatory abstinence on sperm DNA fragmentation and pregnancy rates in IUI cycles, as well as the correlation between the two.
In this prospective randomised study, couples with unexplained infertility were recruited from February 2019 to December 2019.
Both partners then underwent various medical tests to ensure only couples meeting the following criteria participated in this study:
- Infertility for more than 12 months
- 20-40 years old
- regular menstrual cycles
- mid-luteal progesterone levels of > 3 ng/ml
- basal FSH < 12 mIU/ml
- Anti-mullerian hormone (AMH) > 1 ng/ml
- body mass index (BMI) 19–35 kg/m2
- no pelvic pathology noted during transvaginal ultrasound
- bilateral tubal patency checked via hysterosalpingography
- normal semen parameters according to WHO criteria
- body mass index (BMI) 19–35 kg/m2
In addition, female patients diagnosed with endocrine or pelvic pathologies, PCOS, endometriosis, previous pelvic surgery or persistent ovarian cysts, and male patients with varicocele and any accessory gland infections, were excluded from the study.
In the end, 120 couples passed the eligibility criteria and were then prospectively randomised by computer into 2 groups, Group A (ejaculatory abstinence period of 1 day) and Group B (ejaculatory abstinence period of 3 days).
Male participants provided semen samples on the day of IUI with sperm parameters analysed according the WHO guidelines prior to IUI, while sperm cells remaining in the catheter after IUI was used for DNA fragmentation analysis via the TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labelling) method.
Female participants underwent transvaginal ultrasound (TVU) on cycle day 2 or 3 and commenced ovarian stimulation with gonadotropins according to their BMI.
|BMI||Dose of Gonadotropins|
|< 25 kg/m2||75 IU/day|
|≥ 25 kg/m2||150 IU/day|
On the 5th day of ovarian stimulation, another TVU was performed, to measure both ovarian response and the endometrial thickness, with follow-up scans every 2-3days. Dosage of gonadotropins was adjusted according to the ovarian response. If the leading follicle was found to be less than 10µm by day 8 or 9, a 50% increase in dosage was prescribed. Ovulation was then triggered with recombinant hCG (250 mcg) when the leading follicle reached 18µm.
However patients had their cycles cancelled on day 21 if there was
- more than 3 follicles all larger than 15µm or
- no follicle larger than 10µm
Single IUI was carried out 36 hours after r-hCG injection and patients received vaginal micronised progesterone (200 mg twice daily) for luteal phase support.
On the 14th day following IUI, a pregnancy test was performed. Patients returning a positive test underwent a TVU at 6-7weeks of gestation and continued luteal support until 10 weeks of gestation.
For this study, the authors defined clinical pregnancy as 1 or more gestational sacs during TVU, while a plasma β-HCG concentration of > 13 IU/l was recorded as a biochemical pregnancy. If the pregnancy advanced beyond 20 weeks of gestation, it was considered an ongoing pregnancy, whilst pregnancy loss before 20 weeks was deemed a miscarriage.
Of the 120 couples, 14 were excluded during the follow-up phase, as their male partners sperm concentration was less than 15 million/ml on day of IUI.
Initial analysis of baseline characteristics revealed that ninety four (88.7%) couples had primary infertility, and 12 couples (11.3%) had secondary infertility, with both groups similar across all demographic and cycle characteristics.
(n = 52)
(n = 54)
|Age of women (years)||29.2||30.2|
|Age of men (years)||32.5||33.3|
|Duration of infertility (years)||3.6||3.8|
|Type of infertility|
|— Primary infertility (%)||90.4||87.0|
|— Secondary infertility (%)||9.6||13.0|
|Female BMI (kg/m2)||25.7||26.0|
|Male BMI (kg/m2)||27.3||27.7|
|Smoking (in men) (%)||46.2||50.0|
|Basal FSH (IU/l)||7.0||7.0|
|Basal Estradiol (ng/l)||48.2||52.3|
|Basal AFC (n)||11.9||10.7|
|Duration of cycle (days)||11.9||11.6|
|Total gonadotropin dose (unit)||856||854|
|Number of follicles ≥ 18 µm||1.4||1.4|
|Endometrial thickness (mm)||11.5||11.4|
Next, analysis of semen parameters showed that ejaculatory abstinence can significantly impact semen parameters. Group B (3-day abstinence) had significantly higher semen volume, sperm concentration, total sperm count and total progressive motile sperm count (TPMSC) compared to males from group A (1-day abstinence).
Inseminated TPMSC was also significantly higher in group B. However, total sperm motility and progressive sperm motility percentages and perhaps more notably sperm DNA fragmentation were similar between the groups (P>0.18).
(n = 52)
|Sperm concentration (106/ml)||59.0||73.3|
|Total sperm count (× 106)||141.8||232.6|
|Sperm motility (%)||64.3||65.9|
|Total motile sperm count (× 106)||96.4||160.0|
|Progressive motility (%)||52.0||54.1|
|TPMSC (× 106)||79.3||135.5|
|Inseminated TPMSC (× 106)||22.9||33.9|
|Sperm DNA fragmentation (inseminated sperm)||20.7||23.8|
At the same time, analysis of semen parameters according to pregnancy outcomes revealed total sperm count, total progressive motile sperm count, progressive sperm motility, inseminated total progressive motile sperm count, and sperm DNA fragmentation percentages were all similar between IUI cycles with and without pregnancy.
Further statistical analysis concluded that sperm DNA fragmentation percentage was a poor predictor of IUI pregnancy (AUC = 0.578).
Finally, comparison of ejaculatory abstinence and pregnancy rates following IUI, revealed no significant difference between the 2 groups (P= 0.754).
(n = 52)
(n = 54)
|— Ongoing pregnancy (%)||13.5||16.7|
|— Miscarriage (%)||3.8||1.9|
|— Negative (%)||82.7||81.5|
|Exclusion rate (%)*||13.3||10.0|
- Seminal ROS levels and sperm morphology was not analysed.
No external funding was declared for this study.
Antral Follicle Count (AFC)
A test performed via ultrasound to evaluate a female’s ovarian reserve.
Area under the curve (AUC)
The accuracy of a quantitative diagnostic test. (A test AUC = 0.5 has no better accuracy than chance, while test AUC = 1 has perfect accuracy)
A small sac of fluid in the ovary containing an immature egg.
Second half of the menstrual cycle, from ovulation to the start of menstruation.
The probability that a result occurred by random chance.
Open or unobstructed.
An enlargement of the veins within the scrotum.
Thomson L K, et al. (2011). Oxidative deoxyribonucleic acid damage in sperm has a negative impact on clinical pregnancy rate in intrauterine insemination but not intracytoplasmic sperm injection cycles. https://doi.org/10.1016/j.fertnstert.2011.07.356
Muriel L, et al. (2006). Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study. https://doi.org/10.1093/humrep/dei403
Bungum M, et al. (2004). The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. https://doi.org/10.1093/humrep/deh280
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