Session 25 - ALPHA
Questions for Patricia Ann Hunt
- Jc: What recommendation do you have for infertility patients regarding avoiding environmental challenges? How can one change/avoid exposure? What are your thoughts about supplements?
- Steven Gellatly: Question for Patricia - Presumably the detrimental effects of endocrine disruptors follow are dose dependent? If so, is there a critical level at which you see effect i.e. a tipping point? Have you identified factors that may affect a potential tipping point and could these be used to mitigate against the detrimental effects of endocrine disruptors?
- Jc: Most IVF Petri dishes are made of polystyrene. As far as we know this product is probably inert, but free styrene is not. Any thoughts about this? Some labs avoid styrene exposure by prolonged plastic offgassing. Is this something that should be studied in mice?
- Dee Kini: Switching to electric vehicles and reducing CO2 footprint will have any effect on IVF outcomes? This question seems more appropriate for Linda Giudice, but, based on the available evidence, reducing air pollution should enhance fertility in general.
- KANTHARAJ MYSORE SHREEDHARAMURTHY: Key indicators of gamete and Embryo toxicity or stress induced.
- Patricia: I am not certain that I understand the question, but I tried to indicate in my talk that effects are sex-specific. Errors in meiotic chromosome behavior are effectively eliminated during spermatogenesis. In contrast, although large errors may result in oocyte death, oogenesis better tolerates errors - although the result is an increase in aneuploid eggs and embryos.
- KANTHARAJ MYSORE SHREEDHARAMURTHY: How could we conserve & prevent Y chromosome microdeletion?
- Patricia: Sorry, I don’t understand why conservation of a microdeletion is a goal. I am not aware of any evidence that microdeletions are an effect of EDC exposure, although they may be.
- What is the major environmental “disrupter” of fertility ? and is there one that can be reduced/omitted/replaced easily and immediately with more instant effects.
- Patricia: Hmm, this is a judgement call I am not willing to make! ‘Major’ suggests that we know all the disruptors and, quite simply, most significant environmental contaminants have not been studied in sufficient detail..
- Abdallah Mohammed: Any Specific formula to reduce the oxidative stress ? and high DNA fragmented samples?
- Sebo Wang: Is there a current acceptable dose for EDCs exposure? And what was the paper that demonstrated our ability to measure EDC exposure is not effective?
- Patricia: Some would argue that there is no safe dose. The paper is: Gerona et al, 2020, BPA: Have flawed analytical techniques compromised risk assessments? The Lancet Diabetes and Endocrinology
- Anabella Marconetto: There is any evidence about how adult exposure to EDC could affect embryo or oocyte quality (instead of aneuploidy)?
- Patricia: Yes, a number of studies have demonstrated effects on follicle growth and epigenetic reprogramming.
- Hamilton Opurum: the issue of bioaccumulation of these EDCs is very important. Do you think that the use of various plastics in ivf labs could have cumulative effects?
- Patricia: If you are asking if the chemicals could build up in the environment, that’s an interesting question. The only evidence I know of is from washing damaged plastics and in that case it was a matter of cross contamination, not build up.
- Abdallah Mohammed: How can we reduce the high VOCs levels that are made inside the incubator chamber due to the content media, oil, polystyrene and temperature ?
- Patricia: Sorry, I can’t answer this.
- Dr Nelson Vincent: Thanks Prof. Pat for the wonderful presentation. Is there any collaboration between reproductive scientists and the FDA in ensuring some cosmetics that may harbor harmful chemicals to gametogenesis are well regulated or screened before being approved for commercial use? seeing the steady rise in infertility which may not be unconnected to some of these environmental chemicals. Thank you.
- Patricia: CLARITY-BPA was the first collaboration between FDA and academic scientists. Many of us are hoping this study opens the door for more collaborations - and cosmetics and personal care products would be an excellent area for collaboration.
- Laura Diplomatico: For Prof. Hunt: I am a very young scientist and I was wondering, if we are concerned about embryo culture being affected by these compounds during in vitro culture, should we be even more worried when it comes to in vitro follicle culture? In the latter case, the “exposure” to harmful compounds is much longer. Can somehow the refreshing of the culture media be helpful in trying to reduce their amount in the culture dish?
- Patricia: Yes, I think this is a concern. There is considerable evidence that both bisphenols and phthalates can affect follicle growth. Also, since epigenetic reprogramming occurs during follicle growth, this raises the possibility of epigenetic mutations.
Questions for David Mortimer
- Mike Minett: Any feedback on vaping and effects on sperm vitality at this point?
- Steven Gellatly: Question for David - Can you comment on whether the detrimental effects of some vaginal lubricants are reversible i.e. if do sperm recover motility when they are washed out? If so, if sperm in a semen sample containing a lubricant, could the effect of the lubricant on motility be recovered if the sperm are able to enter the cervix (perhaps with muscle contractions during an orgasm?)
- KANTHARAJ MYSORE SHREEDHARAMURTHY: Best known non-toxic sperm stimulants?
- What should we do then to avoid these chemicals? Freeze early??
- Are there any semen preparation methods that help to select against specific sperm with the most damaging effects? What are your thoughts on centrifugation? Microfluidics?
- diego ezcurra: Humans tend to disturb the environmental conditions of normal cells to develop healthy gametes, through medicinal or recreational drugs, environmental or nutritional conditions being the last two big causes of male infertility. Don't you think we are not properly considering the importance of nutrition in the management of male infertility?
- David: The importance of nutrition and lifestyle in fertility are well-established, although they are not my area of expertise. For a very recent review I’d recommend Ciara Wright’s chapter in the following book from CUP
- Abdallah Mohammed: are you recommend the CASA for SA or manual method?
- David: We have discussed the limitations of CASA for human semen analysis many times over the years, e.g. Mortimer ST, van der Horst G, Mortimer D. The future of computer-aided sperm analysis. Asian J Andro. 2015; 17:545-553. doi: 10.4103/1008-682X.154312
To obtain accurate, reliable results we always recommend that semen analysis be performed using manual/visual reference methods, see
Barratt CL, Björndahl L, Menkveld R, Mortimer D. ESHRE special interest group for andrology basic semen analysis course: a continued focus on accuracy, quality, efficiency and clinical relevance. Hum Reprod 2011; 26:3207-3212. doi: 10.1093/humrep/der312
Björndahl L, Barratt CL, Mortimer D, Jouannet P. 'How to count sperm properly': checklist for acceptability of studies based on human semen analysis. Hum Reprod 2016; 31:227-232. doi: 10.1093/humrep/dev305.
- Dr.Hayder A. L. Mossa: How can we balance between the use of detergents and their adverse effects to fertility , especially in the Corona Era?
- David: All detergents by their basic chemical action will damage sperm membranes, so I really don’t see the value in performing in-vitro dose response studies on sperm: we must assume their lethality and control the risks of exposing sperm to them. For example, in our semen collection instructions we have always warned not to allow hand wash soap or similar products to come into contact with the specimen.
- Dr.Bezar Ghan: how's sperm quality on the glycemic index prescriptions
- David: Medical treatments such as this are outside my area of expertise, but presumably a wide range of pharmaceuticals and other products are involved. A quick PubMed search came up with the following paper:
Oliveira JS, Silva AAN, Silva VA Jr. Phytotherapy in reducing glycemic index and testicular oxidative stress resulting from induced diabetes: a review. Braz J Biol 2016; 77:68-78. doi: 10.1590/1519-6984.09915.
Questions for Linda Giudice
- Can seasonal variations in IVF outcomes reflect general air quality during different seasons? Has anybody studied this??
- Other than re-locating, what can patients do to reduce the harmful effects of pollution on their own fertility? Nutritional supplements with antioxidants?
- Steven Gellatly: Question for Linda: How long lived are the effects of air pollution?
- KANTHARAJ MYSORE SHREEDHARAMURTHY: if there is Co2 contamination what alternate filters can be used apart from CODA in Incubators.
- LG: I think my colleagues in IVF labs can answer this question better than I can.
- Lockdown in some areas has reduced urban and industry emissions drastically...will studies perhaps before, during and after the lockdown show changes and reduced preterm and pregnancy loss outcomes?
- LG: Great question. It remains to be seen.
- KANTHARAJ MYSORE SHREEDHARAMURTHY: what percentage of damage could be caused by polyvinyl chloride PVC used in food packaging
- LG: While PVCs can contaminate food, it is unclear what percentage of overall damage is due to this particular class of EDCs.
- Is there not a potential bias in the Xue study from China looking at pollution and fertility in all districts? The fertility rate seems to be the lowest in urban areas as well (just glancing at the two graphs). Was the study corrected for this confounder? - Does the one child policy make any bias?? (rural areas are less compliant usually) Good point
- LG: great questions. These studies are really challenging to conduct. That fertility rates are lowest in urban areas, I do not believe was corrected as a confounder in this study.
- Is the effect of diesel on spermatogenesis reversible? If so, how long should the period of diesel depletion last? 2-3 months?
- LG: I do not believe reversibility has been studied. However, given sperm maturation dynamics, i believe your time estimate is reasonable
- Fernando J Prados Mondéjar: Have you information on the outcome of IVF clinics located in very polluted areas?
- LG: Some of the outcomes in Sao Paolo are worthy of review. That said, the HEPA filters are believed to be most helpful, although miscarriage rates are higher in areas with high PM2.5. Thus, timing of pregnancies seasonally could be considered.
- Naturally occurring “pollutants” just as Radon gas associated with bedrock? Any evidence that it affects fertility? Its effect CA I believe but may be???
- Mohamad alhalabi: is it wise to cosider those environmental factors as chronic affecting generations and inducing developmental changes in reproductive tracts in both females and males causing malformed reproductive ducts and male hypofertilty and increased female reproductive failure likes miscarriage and preterm birth.
- LG: There is a significant literature on this important point - see studies, e.g., by Carmen Williams and Jody Flaws.
- Thanks for your very informative webinar.
- Philip Chan: Are there any evidence to show a negative effect of 5G cell phones and radiating towers on reproductive gametes?
- LG: Not that I am aware of, but important to study.
- MOHAMMED ALRAAWI: if safe to use pentoxifylline or theophylline for icsi and iui samples?
- LG: I would punt this to my IVF Lab Directors’ expertise.
- Frederick Miller: Does anyone care to comment on Phenol red in culture media?
- LG: in most studies of steroid -responsive cells in culture, there is deliberate effort to use charcoal-stripped serum/phenol red-free media.
- Stephen Harbottle: We focus on the importance of air quality in the lab. Is the truth perhaps that the environmental damage is done before the gametes reach our controlled environment?
- LG: Indeed, great questions. Experiments of nature -e.g., wild fires and the COVID19 pandemic with changes in PM2.5 exposures, hopefully will illuminate this point.
- Selwyn Oskowitz: What suggestions for facials , hair coloring during IVf cycle and pregnancy.
- LG: I advise patients considering pregnancy naturally or through assisted reproductive technologies or medically assisted reproduction to use the precautionary principle - limit as much as possible potential “bad actors” as, unfortunately, in most countries harm needs to be proven before being banned.
- Philip Chan: Is anyone aware of reproduction studies proposed for the upcoming planetary MARS mission and effects of cosmic radiation?
- LG: Great question. Apologies - don't know - but good question for space programs.
- Lydia Els-Smit In IVF we presume that in vivo is better than in vitro environment, BUT if ROS and pollutant-effects are present in vivo in the context of idiopathic infertility couples (good eggs, good sperms, good blastocysts but no implantation), is our in vitro lab environment maybe a 'safe' temporary environment?
- LG: Another great question. I think it is a balance of both - safe external and safe internal environment.