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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.

Results

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.

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

Association Between Maternal Caffeine Consumption and Metabolism and Neonatal Anthropometry

CoffeeQuestion

Is maternal caffeine intake associated with neonatal anthropometry?

Findings

In this cohort study of 2055 women from 12 clinical sites, measures of caffeine consumption (plasma caffeine and paraxanthine and self-reported consumption) were associated with neonatal size at birth.

Increasing caffeine measures were significantly associated with lower birth weight, shorter length, and smaller head, arm, and thigh circumference.

A study has found that caffeine consumption during pregnancy, even in amounts less than the recommended 200 mg per day, is linked to smaller neonatal anthropometric measurements.

The longitudinal cohort study in JAMA Network Open concluded that compared to women who drank no, or very little caffeine, women who drank the most caffeine (a plasma caffeine level of ≤ 28 ng/mL) had neonates who weighed 84 g less, were 0.44 cm shorter in length, a 0.28 cm smaller head circumference, a 0.25 cm smaller arm circumference, and a 0.29 cm smaller thigh circumference.

“Most of the research on caffeine and neonatal size at birth focuses on birthweight and length, while relying on self-reported measures of caffeine consumption.,” said senior author Katherine Grantz, MD, an investigator in the Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, in Bethesda, Maryland.

The current study analyzed data from the NICHD Fetal Growth Studies–Singletons, which enrolled 2,055 nonsmoking women at low risk for fetal growth abnormalities with complete information on caffeine consumption from 12 U.S. clinical sites between 2009 and 2013.

“In the NICHD Fetal Growth Studies, we have rich data on multiple measures of neonatal anthropometry to more specifically characterize neonatal size, as well as objective measures of plasma concentrations of caffeine and its primary metabolite, paraxanthine,” Grantz told Contemporary OB/GYN.

The two main sources of caffeine were coffee and soda, which accounted for 35% and 41% of caffeine intake, respectively.

Caffeine was evaluated by both plasma concentrations of caffeine and paraxanthine and self-reported caffeinated beverage consumption measured/reported at 10 to 13 weeks gestation.

Caffeine metabolism was defined as fast or slow, based on genotype information from the single nucleotide variant rs762551.

“Prior caffeine studies have observed lower birthweight after consumption of higher amounts of caffeine — usually 200 to 300 mg, or 2 to 3 cups of coffee, daily,” said Grantz, who served as a co-principal investigator of the NICHD Fetal Growth Studies.

Before starting their analyses, the current authors knew that the average consumption in the sample was much lower, about 35 mg/day, and only 16 women reported drinking more than 200 mg/day.

Because of this low consumption, we were uncertain we would see any significant results, so it was surprising that we still found that increasing caffeine consumption, even at low levels, was associated with some smaller anthropometric measures in the offspring,” Grantz said. “Also, the finding that the decreases in birthweight were manifested by decreases in bone and muscle measures, but not skin folds and fat mass, were unexpected. These findings may indicate decreases in lean tissue as caffeine consumption increases.”

The clinical implications of the study are unknown, considering there were only small reductions in some neonatal anthropometric measures, Grantz said. “Other evidence suggests that even small amounts of caffeine intake during pregnancy (50 mg/day) could be associated with a higher risk of excess growth in infancy and childhood that could put children at higher risk of later cardiometabolic disease,” she said.

“Therefore, our results could indicate some disruption in normal fetal growth patterns, but will require more research to confirm.”

Although the study authors are unable to make recommendations based on the results of their single study, “we encourage pregnant women to talk to their providers about caffeine consumption, and suggest that caution may be warranted,” Grantz said.

The next step for the investigators is to evaluate the serial ultrasounds and fetal volumes conducted throughout pregnancy by the NICHD Fetal Growth Studies to determine when changes begin in fetal growth in relation to caffeine measures, and how these changes may be manifested in fetal volumes.

Disclosure

Grantz reports no relevant financial disclosures.

Reference

Gleason JL, Tekola-Ayele F, Sundaram R, et al. Association between maternal caffeine consumption and metabolism and neonatal anthropometry: a secondary analysis of the NICHD Fetal Growth Studies–Singletons. JAMA Network Open. Published online March 25, 2021. doi:10.1001/jamanetworkopen.2021.3238

Natural Ways to Decrease Oestrogen and Increase Progesterone

Author:Dr. Richard Zeng (Chinese medicine)

Natural Ways to Decrease Oestrogen

women's health

Eat cruciferous vegetables

  • broccoli is the star but eating plenty of green vegetables of the cruciferous family help the liver metabolise oestrogen.
  • Other cruciferous vegetables include: Bok-Choy, Brussels sprouts, Cabbage, Cauliflower, Chinese cabbage, Daikon radish, Horseradish, Kale, Radish, Turnip and Watercress.

Eat high fibre foods to help oestrogen bind in the bowel and assist elimination.

  • One source suggests that eating 1/2 cup of raw grated carrots can be enough fibre to assist in elimination

Decrease alcohol consumption

  • Assist the liver by drinking St Mary’s Thistle and Dandelion tea

Avoid soy

Eat a no sugar and no gluten diet

  • sugar and gluten are both highly inflammatory in susceptible people so should be avoided when possible

Be mindful of too many vitamins, supplements, medications and even caffeine that all need to be processed by the liver, where possible space them out through the day.

Chinese herbal medicine

Some Chinese herbal medicine /formula may help assist in balance your hormone. You may contact us for details.

 

Natural Ways to Increase Progesterone

Reduce stress

  • google progesterone steal if you are more interested in how stress affects progesterone levels

Supplements:

  • 750 mg vitamin C per day (increased progesterone 77% and improved fertility)
  • 600 mg vitamin E (increased progesterone in 67% of patients)
  • 6 g L-arginine (increased progesterone in 71% of patients)

Increasing beta carotene in your diet, as found in:

  • Apricots, Asparagus, Broccoli, Carrots, Chinese cabbage, Chives, Dandelion leaves, Grapefruit, Herbs and spices – chilli powder, oregano, paprika, parsley, Kale, Onions, Peas, Peppers, Plums, Pumpkin, Spinach, Squash, Sweet potatoes. So again, get onto those carrots!

Supplementing with

  • Vitex Agnus Castus 1000mg daily
  • Black Cohosh or as we call it in Chinese Medicine ‘Sheng ma’ on days 1 to 12 (increases progesterone and fertility).

Weight loss

Improving insulin sensitivity (for example metformin increases progesterone levels 246%, chromium supplementation can help in regulating blood sugar in combination with a low sugar and low carbohydrate diet)

  • Replacing saturated fat in the diet with unsaturated fat
  • Eating a high protein, low carbohydrate diet
  • Lowering TSH levels in subclinical hypothyroidism

Chinese herbal medicine

Some Chinese herbal medicine /formula may help assist in balance your hormone. Contact us for details.

Nutrients for Female Fertility Pregnancy Breast Feeding and Beyond

Healthy foodIron

This nutrient is important for the correct formation of foetal blood, brain, eyes, bones and an overall healthy growth rate. It is also vital for a healthy immune system, mucous membranes, for general health and fertility. However many women do not realise how important iron is very important in fertility health. Women with low iron stores could suffer anovulation (no ovulation). In a Harvard University study of 18,500 women, women supplementing iron were 40% less likely to suffer from fertility problems.

During pregnancy there is an increased need for iron due to greater red blood cell mass and plasma volume. Iron should be increased in the 2nd and 3rd trimesters as the foetus will draw on the mother’s iron stores to prepare itself for the 4-6 months after birth (because breast milk is low in iron). Deficiency increases the risk of anaemia, pre-term delivery and low birth weight

Women with low iron are suggested to supplement 10-20mcg daily, however if you are prone to constipation a liquid supplement is more gentle on the stomach; we suggest capsules by bio-ceuticals or liquid spatone.

Also note iron will not be absorbed with calcium, so if taking a supplement make sure to separate these. Inorganic iron supplements can bind up in the gut and cause constipation; they also destroy Vitamin E and compete for absorption with zinc; therefore, use of organic iron supplements and chelates are preferable. Vitamin C enhances the absorption of iron.

Natural sources include green leafy vegetables, dried beans, black strap molasses, lean meat (organic/chemical free), dried apricots, almonds, egg yolk, seaweed, wheat germ, parsley, pumpkin, sesame and sunflower seeds.

Folic acid (B9) and B vitamins

Essential for RNA & DNA formation, it is the most important pre-conception nutrient. Supplementation at least three months prior to conception is suggested, and the need doubles in the first trimester. This is especially so for women who have been on the Pill, as it depletes Vitamin B9 in the body. Prior to conception, make sure your Vitamin B9 intake is around 10mgs per day. During early pregnancy, 25-50mgs of B9 taken 3 times per day can reduce the risk of morning sickness.

Deficiency can lead to infertility and spina bifida. When increasing B9 please note the vitamin is water soluble means that the body only has a limited capacity to store B vitamins (except B12 and folic acid). A person with a poor diet can end up with a deficiency of B vitamins. Delicate means that cooking and processing can reduce amounts in foods; highly processed foods like white flour, have far less than wholegrain counterparts.

Natural sources include dark green leafy vegetables, i.e., uncooked spinach, kale, beet greens; asparagus, broccoli, corn, lima beans, parsnip, mung beans, soy beans; wheat germ; oranges, pineapple, banana. Most of these foods need to be eaten fresh and raw if possible, as B9 is destroyed by heat.

Vitamin D – The sunshine vitamin

I recently saw a new client who works in child care; I asked her if she had any known deficiencies of vitamins. She was not sure so I suggested a blood test with her GP testing all major vitamins including vitamin D, she assured me that her vitamin D would be fine since she spent part of her day outside with the children. Unfortunately she was low in Vitamin D.

Vitamin D has now been strongly linked with temporary infertility. Most of us work and play indoors especially during the colder months. We always advise clients to test their vitamin D levels since 23-49% of Australian’s have a deficiency, and obesity can increase the risk. 10 minutes a day in morning and afternoon sunlight can help correct a slight deficiency however supplements are advised for levels under 50. Supplement 100mcg or 4000iu daily.

Omega 3 fatty acids

Omega 3 is needed for the correct hormone balance; including prostaglandins, increases cervical mucus, helps to promote ovulation and increase the blood flow to the reproductive organs. In pregnancy it aids in the development of the foetal brain and nervous systems. Omega 3 fatty acids contain 2 acids that are essential to health; EPA and DHA. Low levels of DHA, has been linked to depression and other mental health issues.

One study where couples where given 1000mg of omega 3 had a 76.5% verses without omega 50.4% fertilisation rate. Considering that only half of all follicles collected commonly fertilise this could greatly improve the number of viable embryos for transfer.

During pregnancy, a lack of DHA may be associated with premature birth, low birth weight, chromosomal defects, spontaneous abortion, hyperactivity and asthma in children. A recommended daily dose of 500-1000mg daily should be supplemented.

Natural Sources include deep sea ocean/cold water fish (ie. salmon, cod, herring, trout), mono-unsaturated cold-pressed oils (flaxseed especially, walnuts, hemp and chia seeds.

Vitamin E

Assists with conception, a healthy pregnancy and regulates oestrogen levels, improves circulation and protects against varicose veins and haemorrhoids. Vitamin E also helps in the absorption of essential fatty acids and has antioxidant actions as well. Deficiency can lead to spontaneous abortion or cystic fibrosis (with selenium). In later pregnancy Vitamin E will help facilitate an easy delivery.

Sources include sunflower seeds, almonds, organic cold-pressed wheat germ oil, cold-pressed vegetable, seed and nut oils. Best not heated or cooked, i.e., use in salad dressing.

Protein/Amino Acids

Vital for the number and quality of the ovum (eggs) produced the fertilisation process, and the early development of the embryo.

Natural sources include deep sea fish, tofu, legumes ie. lentils, soy beans, kidney beans, eggs (free range), lean organic chemical-free meat and poultry, nuts and seeds, sprouted grains.

Calcium

Essential for the development of the baby’s bones, formulation of nerve tissue and muscles; necessary for controlling blood clotting; makes your fertility mucus ‘stretchy’ and therefore aids ability of sperm to swim through it; aids uterine muscle tone. The foetus requires roughly 30g of elemental calcium to be deposited in the skeleton by the time of delivery (200mg during the 3rd trimester).

If inadequate in the mother’s diet, the supply to the foetus will occur at the expense of the maternal skeleton. Therefore, insufficient calcium supplies during pregnancy and lactation may result in maternal bone loss, reduced breast milk calcium secretion, or impaired infant bone development. If the mother’s diet includes a high proportion of processed foods, soft drinks, high red meat intake, sugar, salt, and alcohol; if she smokes, does not exercise, and consumes caffeine and tea, this will reduce the absorption of calcium. Deficiency can lead to nervous tension, fluid retention, and hypertensive disorders and toxaemia in pregnancy.

Sources include broccoli, cauliflower, soy beans, almonds, sesame seeds, tofu, leafy greens, Brazil nuts, sunflower seeds, unhulled tahini, black strap molasses and kelp (other seaweeds). Dairy foods are another source of calcium; however, since they are not as easily absorbed, it is best to vary your sources of calcium as widely as possible. If you are prone to any sort of mucus congestion such as hayfever, sinus, asthma, recurrent colds/flu or other chest infections, it is best to avoid dairy foods as a source of calcium.

Royal jelly

Royal jelly is a natural bee product; it is rich in amino acids, contains high levels of vitamin D and E, calcium and iron. It is a super food for fertility and been used in Chinese culture for many years. Consider this; the queen bee is only feed royal jelly throughout her lifetime which she will need to lay millions of eggs up to 2000 per day.

Royal jelly has been shown to help balance hormones and increase propensity to mimic human oestrogen, which may help those that suffer from low oestrogen levels. Some evidence exists that royal jelly might also;

  • Improve egg and sperm health
  • Increase libido
  • Reduce inflammation
  • Support the immune system
  • Decrease signs of aging
  • Helps women with irregular cycles

PLEASE DO NOT TAKE IF ASTHMATIC OR ALLERGIES TO BEE’S

Co Q10

CoQ10 is a mitochondrial enzyme. It does multiple jobs in our cells; 1) anti-oxidant, 2) energy production and 3) gene regulation. CoQ10 is the most basic energy currency of our body. Our body makes a huge amount of its own CoQ10, but this ability decreases as we age beyond 35 years.

CoQ10 can be absorbed through supplements and evidence is slowly being accumulated that it could possibly boost a women’s egg health and IVF success rates. It is strongly suggested women older than 35 years wishing to conceive either through IVF or naturally supplement 100-200mg daily preferably in a gel capsule.

PCOS

Clients who have been diagnosed with PCOS can supplement with Chromium and magnesium to help maintain glycaemic control in addition to a low GI diet. Suggested chromium supplementation is between 200-800mcg daily and magnesium between 400-800 mcg daily.

Women’s 7-Years Life Cycle

Author: Dr. Richard Zeng (Chinese medicine)

“Women seven and men eight” is the Chinese statement on the growth cycle of human being from the “Yellow Emperor’s Canon of Internal Medicine“- The “Bible” of Traditional Chinese Medicine (TCM).

That is, the number of women’s life cycle is seven and the number of men’s life cycle is eight. Every seven or eight years, women or men’s life change.The 7 years life cycle is so obvious for woman, and her fertility status changes every seven years too.

The physical change of women occurs obviously every seven years; and men’s change occurs every eight years. – “Yellow Emperor’s Canon of Internal Medicine”

7 year old:

A moman’s kidney energy growing strong, teeth change and hair grows longer and stronger. (the 1st 7 years).

Kidney is a special term in Traditional Chinese Medicine. It not only has the function of controlling the urinary system, but also has a very important role – control the developing, growing, and reproduction. In terms of reproduction, you can think Kidney as a “Small Kidney”- the ovaries or testis.

At the age of 7, a woman’s reproductive system start to develop.

14 year old:

Her menstruation appears as the Ren meridian (the sea of Yin/Essence) flows and the Qi and blood in the Chong meridian (the sea of blood) becomes prosperous, she can have a child. (2nd 7 years)

At the age of 14, her menstruation appears and she is able to have a child. In Traditional Chinese Medicine, the age of menarche is one important factor to help make diagnosis. If menarche is later than 14 year old, often indicate lower fertility energy.

21 year old:

Her kidney energy is balanced, her adult teeth completely developed and her body grows to full height. (3rd 7 years)

A woman’s energy especially fertility energy is full at the age of 21.

28 years old:

Her bones and muscles are strong, her hair grow to full length, her body is at optimal condition. (4th 7 years)

From the age 21 to 28, a women’s fertility energy reach the peak. This is the best time in her life to have children.

35 year old:

Her peak condition declines gradually. Her energy in Yangming meridian declines. Her face starts wither and her hair starts to fall. (5th 7 years)

From 35 year old, she start to have wrinkles on the face, and her general energy and fertility start to decline. She still able to have children.

42 year old:

Sanyang energy declines. Her face wanes and she starts to have white hair. (6th 7 years)

From the age of 42, her physical energy and fertility energy declines and difficult to conceive.

49 year old:

The Ren meridian (Conception Vessel) and Chong meridian vital energy declines, her menstruation dried up, her physique turns old and feeble; She is no longer to conceive. (7th 7 years)

From the 7-year-life cycle, we can see that the good age for a woman to have children is from 21 to 35. And the best age is around 28 year old.

The 7-year life cycle provides a framework for understanding the various phases and developmental milestones in a woman’s life. Each stage presents unique challenges, opportunities, and transitions. By recognising and embracing the changes that accompany each phase, women can navigate their life journeys with self-awareness, resilience, and a focus on their overall well-being.

Additionally, by understanding the women’s 7-year life cycle and following the guidelines for women’s health and natural fertility treatment, women can make informed decisions, maintain their overall health, and address specific needs related to fertility at each stage.

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