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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.

The results of the study showed that, 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.

Reference:

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

Researches Acupuncture Fertility IVF Support

Note: Aphra may not accept these research as evidence. You should consult your treating practitioners about how acupuncture may be able to help you.

Reviews of Acupuncture Chinese medicine for IVF Support

The effects of acupuncture on pregnancy outcomes of in vitro fertilization: a systematic review and meta-analysis.
BMC Complement Altern Med. 2019 Jun 14;19(1):131.

Authors conclusions:

Our analysis finds a benefit of acupuncture for IVF outcomes in women with a history of unsuccessful IVF attempt, and number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings.

https://www.ncbi.nlm.nih.gov/pubmed/31200701

Impact of whole systems traditional Chinese medicine on in-vitro fertilization outcomes
Reproductive BioMedicine Online (2015) 30, 602–612

In this retrospective cohort study, 1231 IVF patient records were reviewed to assess the effect of adjuvant WS-TCM on IVF outcomes compared among three groups:
IVF with no additional treatment;
IVF and elective acupuncture on day of embryo transfer; or
IVF and elective WS-TCM.

The primary outcome was live birth.

Of 1069 non-donor cycles, WS-TCM was associated with greater odds of live birth compared with IVF alone or embryo transfer with acupuncture only.

Of 162 donor cycles, WS-TCM was associated with increased live births compared with all groups (odds Ratio [OR] 3.72; 95% CI 1.05 to 13.24, unadjusted) or embryo transfer with acupuncture only (OR 4.09; 95% CI: 1.02 to 16.38, unadjusted).

Overall, IVF with adjuvant WS-TCM (Whole Systems Traditional Chinese Medicine) was associated with greater odds of live birth in donor and non-donor cycles.

These results should be taken cautiously as more rigorous research is needed.
https://www.rbmojournal.com/article/S1472-6483(15)00092-9/pdf

Effects of Chinese herbs combined with in vitro fertilization and embryo transplantation on infertility: a clinical randomized controlled trial.

J Tradit Chin Med. 2014 Jun;34(3):267-73.

CONCLUSION:
Our findings indicate that Chinese herbs increase endometrial thickness, improve the quality of fertility and embryo, and promote embryonic nidation, thus enhancing the success rate of in vitro fertilization/intracytoplasmic sperm injection-embryo transplantation cycle. Using Chinese herbs improves the outcomes and safety of assisted reproductive technologies.
https://www.ncbi.nlm.nih.gov/pubmed/24992752

Chinese herbal medicine for infertility

Chinese herbal medicine for female infertility: An updated meta-analysis

Complement Ther Med. 2015 Feb;23(1):116-28.

Forty RCTs involving 4247 women with infertility were included in this systematic review.

Author’s conclusions:
Our review suggests that management of female infertility with Chinese herbal medicine can improve pregnancy rates 2-fold within a 3–6 month period compared with Western medical fertility drug therapy.

In addition, fertility indicators such as ovulation rates, cervical mucus score, biphasic basal body temperature, and appropriate thickness of the endometrial lining were positively influenced by CHM therapy, indicating an ameliorating physiological effect conducive for a viable pregnancy.

https://www.sciencedirect.com/science/article/pii/S0965229914001915

Ovarian reserve

Traditional Chinese Medicine for Diminished Ovarian Reserve: A Systematic Review and Meta-analysis

Chinese Herbal Medicines, Volume 6, Issue 2, May 2014, Pages 93-102

Seventeen randomized controlled trials involving 1174 patients were included. Meta-analysis indicated that TCM was superior to Western medicine (WM) in reducing basal serum FSH level, and the effect was more obvious two months after the last, and increasing antral follicle count. The review also revealed the positive role of CMM as an adjuvant to IVF-ET in improving pregnancy rate.

Author’s conclusions:
TCM, with its unique way of replenishing the kidney, may provide an effective and safe alternative therapy to patients with DOR.
https://www.sciencedirect.com/science/article/pii/S1674638414600149

Dysfunction of hypothalamic-pituitary-ovarian axis

Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis.
https://www.ncbi.nlm.nih.gov/pubmed/9330669

PCOS research

Acupuncture for polycystic ovarian syndrome: A systematic review and meta-analysis

Medicine: June 2017 – Volume 96 – Issue 23 – p e7066

We found a low level of evidence that acupuncture is more likely to improve ovulation rate (MD 0.35, 95% CI: 0.14–0.56) and menstruation rate (MD 0.50, 95% CI: 0.32–0.68) compared with no acupuncture. We found statistically significant pooled benefits of acupuncture treatment as an adjunct to medication in luteinizing hormone (LH), LH/follicular stimulating hormone (FSH) ratio, testosterone, fasting insulin, and pregnancy rates, but the level of evidence was low/very low.

https://journals.lww.com/md-journal/fulltext/2017/06090/Acupuncture_for_polycystic_ovarian_syndrome__A.18.aspx

Clinical therapeutic effects of acupuncture combined with Chinese herbal medicine on infertility of polycystic ovary syndrome in the patients with ovulation induction with letrozole

Zhongguo Zhen Jiu. 2018 Jan 12;38(1):27-32.

Author’s conclusions:
For PCOS infertility patients receiving ovulation induction with letrozole, the combined treatment with the Chinese herbal formula for regulating menstruation and removing phlegm and EA remarkably improves the menstrual cycle, reduces body weight and the levels of LH, LH/FSH, T and AMH, improves ovulation and pregnancy rates. This therapy does not induce adverse reactions and the therapeutic effects are better than the simple application of letrozole or the combined therapy of letrozole and Chinese herbal medicine.

https://www.ncbi.nlm.nih.gov/pubmed/29354933

Endometrial receptivity

Acupuncture in improving endometrial receptivity: a systematic review and meta-analysis
BMC Complementary and Alternative Medicinevolume 19, Article number: 61 (2019)

Author’s conclusion:

The efficacy and safety of acupuncture on key outcomes in women with low ER is statistically significant, but the level of most evidence was very low or low. More large-scale, long-term RCTs with rigorous methodologies are needed.

Women’s Sex Hormone

A Literature Review of Women’s Sex Hormone Changes by Acupuncture Treatment: Analysis of Human and Animal Studies.
Evid Based Complement Alternat Med. 2018 Nov 15;2018:3752723

Acupuncture articles including analysis of sex hormones were searched in electronic databases from inception to June 2018. The methodological quality was assessed using modified CAMRADES tool. A total of 23 articles were selected and analyzed.
In the results, overall studies showed that acupuncture increases estrogen, especially estradiol, progesterone, prolactin, and other hormones. Estradiol level was increased in most of studies except 3 studies which resulted in decreased level or not meaningful change. Two studies showed increase of FSH and LH whereas it was decreased in other studies. Other hormones were mostly increased by acupuncture.

CONCLUSION:

This study possibly indicates that acupuncture changes sex hormone in various gynecological conditions in women.

Male infertility sperm quality

The Therapeutic Effects of Traditional Chinese Medicine for Poor Semen Quality in Infertile Males

J Clin Med. 2018 Sep; 7(9): 239.

To further understand the effects of TCM on semen quality, we retrospectively enrolled patients with male infertility and poor semen quality at the Tainan Municipal Hospital in Taiwan between 2013 and 2016. Semen quality analysis in accordance with the WHO criteria is an essential step in the evaluation of male fertility status. Associations between the semen parameters and body mass index, smoking status, alcohol use, duration of infertility, and age were also analyzed.
A total of 126 male infertility patients with abnormal semen analysis were included in this study: 50 TCM users and 13 TCM non-users. The basic characteristics of the two groups were not significantly different.

TCM users account for 92.5% of the total semen improvement subjects.

In conclusion, TCM supplementation may have a beneficial role as improving sperm quality for infertility patients.

Effect of garlic (Allium sativum) on male fertility: a systematic review

A total of 18 experimental studies were included in the study. Thirteen studies evaluated garlic and 5 studies compared garlic effect with adriamycin, titanium dioxide, furan, vitamin E, N-acetylcysteine and cadmium. All studies were conducted in in vivo condition. The results of the studies indicated the potential effect of garlic on enhancing fertility and spermatogenesis, increasing the level of testosterone and improving the testicular structure.

Conclusion: Garlic can increase fertility probably due to its antioxidant properties. However, more clinical trials are recommended.

www.herbmedpharmacol.com/PDF/jhp-5336

The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study

J Herbmed Pharmacol. 2018; 7(4): 306-312.

Of the seventeen patients who continued unprotected intercourse after TKM treatment, twelve had spouses that subsequently conceived spontaneously (70.5%) within a year after TKM. Two patients had babies after intra uterine insemination (IUI) and in vitro fertilization (IVF), respectively.

Authors conclusions

TKM may provide an effective option for infertile male patients with poor semen quality. Further prospective studies with larger populations as well as randomised controlled trials are needed to confirm these results.

https://doi.org/10.1016/j.eujim.2016.01.007

Evaluation of the Spermatogenic Activity of Polyherbal Formulation in Oligospermic Males

Polyherbal formulation (PHF) is one of these herbal amalgams that can be used to treat sexual dysfunction including erectile dysfunction, impotence, ejaculation dysfunction, and hypogonadism. The pilot study was aimed at evaluating the capacity of PHF in enhancing the spermatogenic potential of oligospermic patients.

Authors conclusions

PHF could improve the quantity and quality of semen in a statistically significant manner in oligospermia male adults between the ages of 22 to 40 years, in comparison to the placebo, when used for 90 days, at 750 mg/d in three doses. PHF does also improve the serum testosterone; LH; and FSH level in a majority of PHF treated males, in comparison to the placebo.

The results suggested that the prepared PHF may be a new auspicious novel therapeutic amalgamation, which can be used to improve the spermatogenic potential of many oligospermic infertile men.

This spermatogenic property may be due to possible synergistic action of selected herbs’ parts used in the preparation of PHF. However, further investigations are warranted to confirm and elucidate the effect of PHF on semen parameters.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review

World J Mens Health. 2019 May; 37(2): 175–185.

Overall, the effectiveness of TCM for Male Infertility has been confirmed by numerous studies, but many problems exist in these studies. The advantages of TCM and the differences between TCM and Western medicine, as well as unsolved problems and solutions, are summarized.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479084/#B55

Effect of Chinese Herbal Medicine on Male Infertility.

Int Rev Neurobiol. 2017;135:297-311

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 indentify the new drugs from CHM and ensure safety, efficacy, and consistency of CHM.

https://www.ncbi.nlm.nih.gov/pubmed/28807164

Best Acupuncture Protocols for Infertility IVF and IUI

From http://www.healthcmi.com

New research demonstrates a consensus amongst acupuncture experts on best practice treatment protocols for acupuncture enhancement of assisted reproductive technology (ART) fertility treatments. ART includes all fertility treatments in which both the eggs and sperm are handled. ART includes in vitro fertilization (IVF) and intrauterine insemination (IUI).

traditional needle acupuncture

In this study, researchers set out to determine if a consensus exists on high priority acupuncture points for the enhancement of ART. Acupuncture IVF and IUI ART has been used in the USA since 1981 to help women become pregnant. Although acupuncture and Chinese medicine for the treatment of infertility is a time honored practice, the combination of acupuncture with ART has emerged in recent years as an effective approach for improving pregnancy and live birth rates.

In this study, researchers administered three rounds of questionnaires to fifteen international acupuncture fertility experts to determine if a consensus exists on best practice protocols. The investigation revealed that several key components are central to acupuncture in combination with ART.

The timing of an acupuncture treatment in relation to the menstrual cycle is of great importance. An acupuncture treatment administered between day 6 and 8 of the “stimulated ART cycle” is optimal. In addition, it is ideal to have two acupuncture treatments “on the day of embryo transfer.”

Pre-transfer acupuncture points of high priority are

SP8, SP10, Liv3, ST29 and CV4.

Post-transfer points include

GV20, K3, SP6, P6 and K3.

Auricular acupuncture points Shenmen and Zigong were also determined to be of high priority.

About the Healthcare Medicine Institute: HealthCMi provides online acupuncture CEU credit to licensed acupuncturists and publishes current events related to acupuncture, herbal medicine and important innovations in healthcare technology.

 

References

  1. BMC Complementary and Alternative Medicine 2012, 12:88 doi 10.1186/1472-6882-12-88. 7 July 2012.
  2. Development of an acupuncture treatment protocol by consensus for women undergoing Assisted Reproductive Technology (ART) treatment. Caroline A Smith, Suzanne Grant, Jane Lyttleton and Suzanne Cochrane. ?Zhongguo Zhen Jiu. 2012 Feb;32(2):113-6.
  3. Effects of electroacupuncture on embryo implanted potential for patients with infertility of different symptom complex]. Kong FY, Zhang QY, Guan Q, Jian FQ, Sun W, Wang Y. Department of Reproduction, The Second Affiliated Hospital of Shandong University of TCM, Jinan, China. Fertil Steril. 2005 Jan;83(1):30-6.
  4. Secretion of human leukocyte antigen-G by human embryos is associated with a higher in vitro fertilization pregnancy rate. Yie SM, Balakier H, Motamedi G, Librach CL.

Impact of whole systems traditional Chinese medicine on in-vitro fertilization outcomes

By Lee E.

Declaration: Support provided by NIH/NCCAM grant R25 AT002879 (Suppl) and 1K23AT006392. LHR owned the acupuncture practice. The authors report no financial or commercial conflicts of interest.

Highlights

  • Whole Systems Traditional Chinese Medicine (WS-TCM) added to IVF may be beneficial.
  • WS-TCM and IVF was associated with more live births compared with acupuncture and IVF.
  • WS-TCM and IVF was associated with more live births compared with IVF alone.
  • WS-TCM is individualized and includes acupuncture and other TCM interventions.

Abstract

Patients undergoing IVF may receive either acupuncture or whole-systems traditional Chinese medicine (WS-TCM) as an adjuvant IVF treatment. WS-TCM is a complex intervention that can include acupuncture, Chinese herbal medicine, dietary, lifestyle recommendations.

In this retrospective cohort study, 1231 IVF patient records were reviewed to assess the effect of adjuvant WS-TCM on IVF outcomes compared among three groups:

  • IVF with no additional treatment;
  • IVF and elective acupuncture on day of embryo transfer; or
  • IVF and elective WS-TCM.

The primary outcome was live birth.

Of 1069 non-donor cycles, WS-TCM was associated with greater odds of live birth compared with IVF alone (adjusted odds ratio [AOR] 2.09; 95% confidence interval [CI] 1.36 to 3.21), or embryo transfer with acupuncture only (AOR 1.62; 95% CI 1.04 to 2.52). Of 162 donor cycles, WS-TCM was associated with increased live births compared with all groups (odds Ratio [OR] 3.72; 95% CI 1.05 to 13.24, unadjusted) or embryo transfer with acupuncture only (OR 4.09; 95% CI: 1.02 to 16.38, unadjusted).

Overall, IVF with adjuvant WS-TCM was associated with greater odds of live birth in donor and non-donor cycles. These results should be taken cautiously as more rigorous research is needed.

Researches of Chinese Herbal Medicine and fertility

Efficacy of Traditional Chinese Herbal Medicine in the management of female infertility: a systematic review.

Ried K1, Stuart K. Complement Ther Med. 2011 Dec;19(6):319-31. doi: 10.1016/j.ctim.2011.09.003. Epub 2011 Oct 5.

Conclusions

Review suggests that management of female infertility with Chinese Herbal Medicine can improve pregnancy rates 2-fold within a 4 month period compared with Western Medical fertility drug therapy or IVF. Assessment of the quality of the menstrual cycle, integral to TCM diagnosis, appears to be fundamental to successful treatment of female infertility.

 

 

Chinese herbal medicine for female infertility: an updated meta-analysis.

Ried K1.Complement Ther Med. 2015 Feb;23(1):116-28. doi: 10.1016/j.ctim.2014.12.004. Epub 2015 Jan 3.

Methods

We searched the Medline and Cochrane databases until December 2013 for randomized controlled trials and meta-analyses investigating Chinese herbal medicine therapy for female infertility and compared clinical pregnancy rates achieved with CHM versus WM drug treatment.

Results

Forty RCTs involving 4247 women with infertility were included in our systematic review. Meta-analysis suggested a 1.74 higher probability of achieving a pregnancy with CHM therapy than with WM therapy alone (risk ratio 1.74, 95%CI: 1.56-1.94; p<0.0001; odds ratio 3.14; 95%CI: 2.72-3.62; p<0.0001) in women with infertility. Trials included women with PCOS, endometriosis, anovulation, fallopian tube blockage, or unexplained infertility. Mean pregnancy rates in the CHM group were 60% compared with 33% in the WM group.

Conclusions

Our review suggests that management of female infertility with Chinese herbal medicine can improve pregnancy rates 2-fold within a 3-6 month period compared with Western medical fertility drug therapy. In addition, fertility indicators such as ovulation rates, cervical mucus score, biphasic basal body temperature, and appropriate thickness of the endometrial lining were positively influenced by CHM therapy, indicating an ameliorating physiological effect conducive for a viable pregnancy.

 

 

Unexplained Infertility Treated with Acupuncture and Herbal Medicine in Korea

Jongbae J. Park, K.M.D., Ph.D.J Altern Complement Med. 2010 Feb; 16(2): 193–198.

Conclusions

The standard therapeutic package for unexplained infertility in women studied here is safe for infants and the treated women, when administered by licensed professionals. While it remains challenging to have the target population complete a 6-month treatment course, during which most patients have to pay out of pocket, the extent of successfully achieved pregnancy in those who received full treatment provides meaningful outcomes, warranting further attention. A future study that includes subsidized treatment costs, encouraging the appropriate compliance rate, is warranted.