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Oocyte ability to repair sperm DNA fragmentation: the impact of maternal age on intracytoplasmic sperm injection outcome

An estimated 15% of couples in the world suffer from infertility. According to a survey in 2013 by the National Institute of Health and Clinical Optimization (NICE) in the United Kingdom, male factors have become the main reason for infertile couples to use assisted reproductive therapy (ART).

Male infertility is mainly diagnosed by routine semen analysis (WHO standard), including semen volume, concentration, vitality and morphology.

Although studies have shown that semen quality and ART outcome are correlated, until now, we have not found a conventional semen threshold that can predict the success of ART.

Recent studies have shown that sperm DNA fragmentation (SDF), including sperm DNA single-strand breaks and double-strand breaks, are all related to male infertility factors, which can adversely affect the male reproductive system and increase the risk of genetic diseases in offspring .

Two previous Meta-analysis studies have shown that SDF is related to ART failure and repeated pregnancy loss.

However, human sperm itself does not have DNA repair activity (DRA). Once fertilised, DRA mainly depends on the transcripts produced during the maturation of the oocyte to repair it. The ability of oocytes to repair SDF depends on the degree of fragmentation of SDF and the quality of oocytes.

Therefore, reproductive medicine researchers from Sao Paulo, Brazil, conducted research on women’s age and SDF and the outcome of intra-cytoplasmic sperm injection (ICSI) assisted pregnancy.

Amanda Souza Setti et al. collected 540 couples who underwent ICSI at the centre from May 2017 to December 2019, and divided the ICSI cycle into three groups according to the age of the woman: ≤36 years old (285 cases), 37-40 years old ( 147 cases) and >40 years old (108 cases).

sperm fragmentation ICSI

Sperm chromatin diffusion test was used to evaluate the SDF of semen specimens.

For each age group, according to the SDF index, the ICSI cycle is divided into two subgroups: low fragmentation index (SDF <30%) and high fragmentation index (SDF ≥ 30%).

Summarised and analysed the outcome indicators such as embryo implantation rate, pregnancy rate and abortion rate.

The study found that: for young patients (36 years old) and patients between 37-40 years old, whether SDF <30% or SDF ≥ 30%, the laboratory and clinical results of the ICSI cycle were not significantly different.

When female patients are older than 40 years old, compared with SDF<30%, in an ICSI cycle with SDF ≥ 30%, the rate of D3 high-quality embryo acquisition (54.4% vs 33.1%) and the rate of blastocyst formation (49.6% vs 30. 2%), pregnancy rate (20.0%vs7.7%) and implantation rate (19.7%vs11.9%) were significantly reduced, while miscarriage rate (12.5%vs100.0%) increased.


This study showed older oocytes, when injected with sperm derived from samples with high SDF (Sperm DNA Fragmentation) index, develop into embryos of poor quality that lead consequently to lower implantation and pregnancy rates and higher miscarriage rates, in intracytoplasmic sperm injection cycles from women with advanced maternal age.

The results of this study are of great significance to clinical work:

Women’s age cannot be changed, but male SDF can be improved through diet, environment, lifestyle changes, antioxidant and other therapies. 

This study may provide new ideas for improving the ART pregnancy rate of elderly couples and reducing the abortion rate.


Oocyte ability to repair sperm DNA fragmentation: the impact of maternal age on intracytoplasmic sperm injection outcomes

Fertility and Sterility (IF7.329), Pub Date : 2021-02-13, DOI: 10.1016/j.fertnstert.2020.10.045

Amanda Souza Setti, Daniela Paes de Almeida Ferreira Braga, Rodrigo Rosa Provenza, Assumpto Iaconelli, Edson Borges

Acupuncture treatment of male infertility: a systematic review

Zhonghua Nan Ke Xue. 2015 Jul;21(7):637-45.
He Y, Chen CT, Qian LH, Xia CL, Li J, Li SQ, Liu BP.


To systematically evaluate acupuncture as a treatment for male infertility.


We searched Chi na Biology Medical Database (CBM), Wan Fang Medical Information System, China National Knowledge Infrastructure (CNKI), VIP Information Resource System (VIP), and PubMed for published literature on acupuncture as a treatment for male infertility on May 1 2014. Based on the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA), we evaluated the quality of the reports, conducted meta-analysis on the identified studies via RevMan5.2, and assessed the quality of the evidence in the literature by Grading of Recommendations Assessment, Development, and Evaluation (GRADE).


A total of 12 studies involving 2,177 patients were included, the quality of which was evaluated as mediocre. With regard to the cure rate, acupuncture was comparable to traditional Chinese medicine (TCM) (P > 0.05) but better than Western medicine (RR = 4.00, 95% CI 1.63 to 9.82, P < 0.01) while acupuncture + TCM was better than either TCM (RR = 1.77, 95% CI 1.20 to 2.60, P < 0.01) or Western medicine used alone (RR = 2.73, 95% CI 1.51 to 4.93, P < 0.01), and acupuncture + Western medicine was better than Western medicine alone (RR = 1.88, 95% CI 1.17 to 3.02, P = 0.01). The combined use of acupuncture, ear pressure, TCM, and Western medicine showed a higher cure rate than the combination of TCM and Western medicine (RR = 3.45, 95% CI 2.90 to 4.11, P < 0.01). In therapeutic effectiveness, acupuncture was comparable to TCM (P > 0.05) but superior to Western medicine (RR = 1.41, 95% CI 1.12 to 1.71, P < 0.01), acupuncture + TCM was superior to either TCM (RR = 1.14, 95% CI 1.05 to 1.23, P < 0.01) or Western medicine alone (RR = 1.43, 95% CI 1.22 to 1.67, P < 0.01), and acupuncture + Western medicine was superior to Western medicine alone (RR = 1.25, 95% CI 1.05 to 1.49, P = 0.01). In improving sperm concentration, acupuncture was as effective as TCM (P > 0.05) and sham acupuncture (P > 0.05) but outdid Western medicine (RR = 27.00, 95% CI 24.27 to 29.73, P < 0.01) and acupuncture + TCM outdid either TCM (RR = 14.65, 95% CI 7.58 to 21.72, P < 0.01) or Western medicine alone (RR = 1.04, 95% CI–1.43 to 3.51, P > 0.05). In improving grade a sperm, acupuncture exhibited a similar effect to TCM (P > 0.05) and sham acupuncture (P > 0.05), and acupuncture + TCM was more effective than TCM alone (RR = 7.78, 95% CI 3.51 to 12.23, P < 0.01) but equally effective as Western medicine (P > 0.05). In elevating the level of grade a + b sperm, acupuncture + TCM excelled either TCM (RR = 11.00, 95%, CI 3.17 to 18.82, P < 0.01) or Western medicine alone (RR = 12.22, 95% CI 6.87 to 17.57, P < 0. 01), while acupuncture produced a comparable effect with sham acupuncture (P > 0.05). As for the quality of the included studies, only 3 conclusions of the 23 meta-analyses were assessed to be of average quality, while the others of poor or extremely poor quality. Therefore, the recommendation grade of the conclusions was low.


For the treatment of male infertility, acupuncture is reported to be equally effective as TMC and more effective than Western medicine, and its effectiveness is enhanced when applied in combination with either TCM or Western medicine. Acupuncture is distinctively efficacious in improving sperm quality. Nevertheless, the overall quality of the included studies is low.

Acupuncture male infertility research

Influence of acupuncture on idiopathic male infertility in assisted reproductive technology

J Huazhong Univ Sci Technolog Med Sci. 2002;22(3):228
Zhang M, Huang G, Lu F, Paulus WE, Sterzik K.
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.

The clinical effects of acupuncture on idiopathic male infertility in sperm parameter and on therapeutic results in assisted reproductive technology were investigated. 22 patients failed in intracytoplasmic sperm injection (ICSI) with idiopathic male infertility were treated with acupuncture twice weekly for 8 weeks, followed by ICSI treatment again. The sperm concentration, motility, morphology, fertilization rates and embryo quality were observed. Quick sperm motility after acupuncture (18.3% +/- 9.6%) was significantly improved as compared with that before treatment (11.0% +/- 7.5%, P < 0.01). The normal sperm ratio was increased after acupuncture (21.1% +/- 10.4% vs 16.2% +/- 8.2%,P < 0.05). The fertilization rates after acupuncture (66.2%) were obviously higher than that before treatment (40.2%, P < 0.01). There was no significant difference in sperm concentration and general sperm motility between before and afteracupuncture. The embryo quality after acupuncture was improved, but the difference between them was not significant (P > 0.05). Acupuncture can improve sperm quality and fertilization rates in assisted reproductive technology.

PMID: 12658811 [PubMed-indexed for MEDLINE]

Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study

Andrologia Volume 32 Issue 1 Page 31 January 2000
S. Siterman, F. Eltes, V. Wolfson, H. Lederman & B. Bartoov

Classic therapies are usually ineffective in the treatment of patients with very poor sperm density. The aim of this study was to determine the effect of acupuncture on these males. Semen samples of 20 patients with a history of azoospermia were examined by light microscope (LM) and scanning electron microscope (SEM), with which a microsearch for spermatozoa was carried out. These examinations were performed before and 1 month after acupuncture treatment and revealed that the study group originally contained three severely oligoteratoasthenozoospermic (OTA), two pseudoazoospermic and 15 azoospermic patients. The control group was comprised of 20 untreated males who underwent two semen examinations within a period of 24 months and had initial andrological profiles similar to those of the experimental group. No changes in any of the parameters examined were observed in the control group. There was a marked but not significant improvement in the sperm counts of severely OTA males following acupuncture treatment (average=0.7±1.1 10 6 spermatozoa per ejaculate before treatment vs. 4.3±3.2 10 6 spermatozoa per ejaculate after treatment). A definite increase in sperm count was detected in the ejaculates of 10 (67%) of the 15 azoospermic patients. Seven of these males exhibited post-treatment spermatozoa that were detected even by LM. The sperm production of these seven males increased significantly, from 0 to an average of 1.5±2.4 10 6 spermatozoa per ejaculate (Z= 2.8, P <0.01). Males with genital tract inflammationexhibited the most remarkable improvement in sperm density (on average from 0.3±0.6 106 spermatozoa per ejaculate to 3.3±3.2 10 6spermatozoa per ejaculate; Z=2.4, P 0.02). Two pregnancies were achieved by the IVF-ICSI procedure.It is concluded thatacupuncture may be a useful, nontraumatic treatment for males with very poor spermdensity, especially those with a history of genital tract inflammation.

Modification of semen quality by acupuncture in subfertile males

[Article in German]
Geburtshilfe Frauenheilkd. 1984 Aug;44(8):510
Fischl F, Riegler R, Bieglmayer C, Nasr F, Neumark J.

Our first attempt in treating subfertility by acupuncture was carried out on 28 males. The results obtained from the experiences in veterinary medicine encouraged us to attempt this type of therapy. Each patient received a total of 10 treatments for a period of three weeks. Several spermiograms were made afterdiagnosis subfertility. We checked spermiograms and hormone levels before and after acupuncture. Total count, concentration and motility were evaluated. In all cases we observed a statistically significant improvement of sperm quality. Having obtained these good results in our first studies, we now intend to continue acupuncture therapy in subfertile males for insemination or intercourse at the time of the ovulation of their female partners.

PMID: 6566639 [PubMed-indexed for MEDLINE]

Male fertility Chinese medicine acupuncture research

The Therapeutic Effects of a Traditional Chinese Medicine Formula Wuzi Yanzong Pill for the Treatment of Oligoasthenozoospermia: A Meta-Analysis of Randomized Controlled Trials

In this 2018 study of a traditional Chinese herbal formula and its effects for men with low sperm count and sperm with poor motility “…the WZYZ pill improved sperm quality by improving several semen parameters and decreasing DNA damage in oligoasthenozoospermia patients.

Evidence-Based Complementary and Alternative Medicine, Volume 2018 (2018), Article ID 2968025, 10 pages


Ming Peng Zhao, Xiao Shi, Grace Wing Shan Kong, Chi Chiu Wang, Justin Che Yuen Wu, Zhi Xiu Lin, Tin Chiu Li, and David Yiu Leung Chan

Published 17 January 2018

Oligoasthenozoospermia is a crucial factor in male infertility. Wuzi Yanzong (WZYZ) pill is a popular traditional Chinese medicine (TCM) formula which has been used for male infertility treatment for years. However, its effects on semen quality remain controversial. We conducted a preregistered meta-analysis to assess the effect of WZYZ pill for the therapeutic effects on oligoasthenozoospermia. Five randomized controlled trials including 960 participants were selected from databases of domains in North-East Asian regions, PubMed, Embase, and Cochrane Library.

WZYZ pill group yielded a greater mean increment on sperm concentration (5 trials: MD 5.99, 95% CI 2.12–9.85, ), sperm motility (5 trials: MD 4.57, 95% CI 0.47–8.68, ), sperm morphology (2 trials: MD −1.93, 95% CI −4.87–1.01, ), activity of acrosomal enzyme (2 trials: MD 28.27, 95% CI 12.41–44.14, ), volume of semen (2 trials: MD 0.56, 95% CI 0.21–0.91, ), and a decrement of sperm DNA fragmentation index (2 trials: MD −3.82, 95% CI −6.45–−1.19, ). However, qualities of selected studies were generally unsatisfactory, and there was inherent heterogeneity among some of the outcomes.

Despite these limitations, the WZYZ pill improved sperm quality by improving several semen parameters and decreasing DNA damage in oligoasthenozoospermia patients.


Effect of Chinese Herbal Medicine on Male Infertility

“Chinese Herbal Medicine improved sperm motility and quality, increased sperm count and rebalanced inadequate hormone levels, and adjusted immune functions leading to the increased number of fertility. Further, CHM in combination with conventional therapies improved efficacy of conventional treatments.”

International Review of Neurobiology, Volume 135, 2017, Pages 297-311 : Chapter Thirteen – Effect of Chinese Herbal Medicine on Male Infertility




Male infertility normally refers a male’s inability to cause pregnancy in a fertile female partner after 1 year of unprotected intercourse. Male infertility in recent years has been attracting increasing interest from public due to the evidence in decline in semen quality. There are many factors contributing to the male infertility including abnormal spermatogenesis; reproductive tract anomalies or obstruction; inadequate sexual and ejaculatory functions; and impaired sperm motility, imbalance in hormone levels, and immune system dysfunction. Although conventional treatments such as medication, surgical operation, and advanced techniques have helped many male with infertility cause pregnancy in their female partners, effectiveness is not satisfactory and associated with adverse effects.

Chinese herbal medicine (CHM) has been used to improve male infertility in China for a very long time and has now been increasingly popular in Western countries for treating infertility. In this chapter we summarized recent development in basic research and clinical studies of CHM in treating male infertility.

It has showed that CHM improved sperm motility and quality, increased sperm count and rebalanced inadequate hormone levels, and adjusted immune functions leading to the increased number of fertility. Further, CHM in combination with conventional therapies improved efficacy of conventional treatments. More studies are needed to identify the new drugs from CHM and ensure safety, efficacy, and consistency of CHM.

Randomised clinical trial of comparing effects of acupuncture and varicocelectomy on sperm parameters in infertile varicocele patients

A 2016 study comparing acupuncture vs surgery for men with varicocele found “acupuncture treatment in primary infertile varicocele patients with semen abnormalities seems to be effective and has comparable results with the varicocelectomy treatment.”

Eyup Veli Kucuk, MD, Umraniye Education & Research Hospital, Adem Yavuz Cad. No:1, Elmalikent Mah., 34760 Umraniye, İstanbul, Turkey.

Andrologia. First published: 21 January 2016


The aim of the study was to evaluate the effect of the acupuncture treatment on sperm parameters and pregnancy rates in patients with primary infertility. Between January 2008 and May 2010, 30 men with the primary infertility (one year of unprotected intercourse, healthy wife) and varicocele with normal hormone levels and abnormal semen analysis were randomised into two groups. Group 1 underwent subinguinal microscopic varicocelectomy, and Group 2 underwent acupuncture treatment twice a week for 2 months. Both groups were evaluated with semen analysis at 6 months after the treatment. Patients in both groups evaluated with telephone calls and e-mail in terms of pregnancy. The mean age of the patients was 27.2, and groups were comparable regarding the age (P = 0.542). The pre-treatment sperm concentration, motility and morphological characteristics were similar in both groups. Sperm concentration and motility improved significantly in both groups after the treatment. Increase in sperm concentration was higher in the acupuncture group compared to the varicocelectomy group (P = 0.039). The average follow-up was 42 months, and pregnancy rates were emphasised 33% in both groups. Acupuncture treatment in primary infertile varicocele patients with semen abnormalities seems to be effective and has comparable results with the varicocelectomy treatment.