Understanding the onset of embryonic arrest by studying the morphology of the embryos at different stages of their development is a relatively well-understood subject. The qualitative nature of the study makes it difficult to determine and quantify the causes behind the arrest. For successful embryonic development, it is essential to know, non-destructively, and the developmental viability of the embryos at a particular stage.
We investigate the bulk stiffness and recovery time as the viability quantifiers for grading or classifying embryos at the two-cell stage or after the formation of the first cleavage. A simple cantilever beam-based experimental procedure is established to investigate two-cell mouse embryos in two distinct orientations.
Bulk stiffness measurement varies with the embryo’s orientation and deformation. A good quality two-cell embryo shows a significant decrease in stiffness ratio with the deformation. Also, the embryo’s recovery time after releasing deformation may indicate a quality-dependent correlation.
Our study concludes that the bulk stiffness measurements in the two principal orientations, their ratio, and recovery time correlate with the underlying morphology of two-cell stage mouse embryos.
Guidelines for Antenatal, Intranatal and Postnatal and New-born Management of COVID-19
The unprecedented scale of coronavirus infections or COVID-19 pandemic has affected the lives of millions of people across the globe. This has put tremendous strain on the health-care facilities and doctors, who are facing the direct brunt of this crisis and face numerous challenges in diagnosing and treating the affected people.
The central and state governments have been
actively working with medical bodies such as ICMR and health-care facilities to
formulate management guidelines for effectively tackling the growing number of
COVID-19 infections.
Some of the most vulnerable population groups in this COVID-19 pandemic are pregnant mothers, mothers who have recently delivered a child and new-born babies. The National Neonatology Forum’s (NNF) Karnataka State Chapter has taken the initiative to draft and issue the “Guidelines for Antenatal, Intranatal and Postnatal and New-born Management of COVID-19”.
The NNF Karnataka State Chapter has prepared a comprehensive and evidence-based set of guidelines for the diagnosis and management of COVID-19 during pregnancy and delivery. It has been prepared by leading and eminent Neonatologists, Gynaecologists and Obstetricians from Karnataka.
This guideline prescribing standard operating procedures (SOPs) for the management of pregnant mothers and new-borns was released on 24th July 2020. The guideline has been duly endorsed by the Honourable Chief Minister of Karnataka, Shri BS Yediyurappa, Deputy Chief Minister, Dr. Ashwath Narayan CN, Honourable Health Minister of Karnataka, Shri B. Sreeramulu and Honourable Medical Education Minister, Dr. K. Sudhakar.
Brief Background of COVID-19
Towards the end of 2019, a coronavirus was identified to be the cause of a cluster of pneumonia cases in the city of Wuhan in China. The virus rapidly reached an epidemic scale across China and subsequently throughout the world. In February 2020, the World Health Organization (WHO) designated the disease caused by the coronavirus as COVID-19.
Recent studies have reported a variation in the viral genome of the coronavirus which has improved its ability to infect human cells. It has now become the dominant strain responsible for most COVID-19 cases. Common symptoms include fever, cough, sore throat, breathing issues, headache, and abdominal pain.
The coronavirus is primarily transmitted through close-range person-to-person contact mainly via respiratory droplets from an infected individual. Other modes of transmission are airborne, fomite, faecal-oral, blood born, and mother to child. Globally there are now close to 24 million confirmed COVID-19 cases and 3.2 million cases in India alone as of August 2020.
Management of COVID-19 and Pregnancy
Pregnant women undergo physiological and immunological changes. In the case of COVID-19 infection, most pregnant women experience mild or moderate symptoms. With the existing data, there is no evidence of an increased risk of miscarriage in COVID-19 positive mothers. The risk of vertical transmission or transmission from mother to foetus is also very low. Transmission of COVID-19 from breast milk to baby is extremely rare.
Source: NNF Karnataka State Chapter: Guidelines for Antenatal, Intranatal and Postnatal and New-born Management of COVID-19, July 2020
Highlights of Guidelines for Obstetric Health Care
All pregnant women will be treated as COVID-19 suspects and all precautionary measures will be followed.
The pregnant patient will be placed in a separate ward, negative pressure will be maintained in the Operation theatres (OT), the patients will wear a triple-layer mask.
All healthcare professionals must wear Personal Protection Equipment (PPE).
The Department of health and family welfare should be immediately notified for suspected COVID-19 cases and testing should be done at Government accredited labs.
The healthcare centres must maintain a registry of confirmed COVID-19 cases.
Healthcare centres will follow universal mask policy i.e. all visitors, patients, doctors, medical and non-medical staff will wear masks.
Sanitization of diagnostic equipment such as ultrasound machines will be done after each use.
Criteria for testing for COVID-19
Under certain circumstances, the pregnant patient will be needed to undergo testing for COVID-19. The following criteria will be used to prescribe the COVID-19 test:
Symptomatic persons will travel history in the past 14 days.
Patients with severe respiratory illness.
An asymptomatic person who has had direct contact with confirmed COVID-19 case.
In addition, ICMR has announced mandatory testing of patients living in COVID-19 hotspots or containment zones even if they are asymptomatic.
Management of pregnant patients with COVID 19
Most COVID-19 positive pregnant patients exhibit only mild symptoms. Severe symptoms are observed among immunosuppressed patients and patients with chronic conditions such as diabetes, lung disease, etc. Nevertheless, apart from the general precautions, particular considerations will be given to pregnant patients with COVID-19. Some of these include:
Maintaining
high oxygen levels and keep saturations > 94%.
Conduct
radiographic investigations such as chest X-ray using abdominal shielding.
Periodic
blood analysis to monitor white blood cell count and prescribe antibiotics when
necessary.
Current
guidelines however do not recommend the use of Hydroxychloroquine or
antiviral drugs in pregnant women.
Postnatal care for mothers with COVID-19
Limited information is available on the severity of COVID-19 symptoms exhibited in new-born babies born to mothers with COVID-19. However, the risk of transmission from mother to child after birth exists. Individualized care is recommended on a case-to-case basis after a thorough risk and benefit analysis with neonatologists and the concerned families.
Breastfeeding guidelines for mothers with COVID-19
It is extremely rare for transmission of COVID-19 from mother to baby through breast milk. It is strongly recommended to initiate breastfeeding within 1 hour of birth and that the baby is exclusively breastfed for the first 6 months.
Source: NNF Karnataka State Chapter: Guidelines for Antenatal, Intranatal and Postnatal and New-born Management of COVID-19, July 2020
Mothers confirmed with COVID-19 should breastfeed the baby with facemask and practice hand hygiene.
Face-mask should be worn during all events of contact with new-born.
If the baby and mother are required to be separated temporarily, expressed breast milk is strongly recommended to be given to the new-born by a healthy caregiver.
Gloves must be worn by the caregiver when receiving bottles of expressed breast milk. After securing the cap, the bottles should be wiped with viricidal wipes and air-dried on a clean surface.
In addition, the NNF Karnataka State Chapter also provides general guidelines for Basic Hospital Management, Visitor Policy, Managing Biomedical Waste, Mental Health and Wellness support for Patients and Healthcare Professionals and District Wise Government Helpline numbers in Karnataka.
Acknowledgements: We would like to acknowledge the Dr. Prashnath and Dr. Jyothi Bandi from LittleBaby Clinic for kindly permitting us to disseminate this information for the benefit of all.
Our ever-changing and rapidly evolving urban lifestyle is fueled by technology innovations in IT – telecom, medicine and food. These innovations have significantly improved the quality of our life in terms of superior digital connectivity and access to information, easy access to quality healthcare services and food commodities. However, our modern lifestyle and occupational activities have also put us under increased exposure to various potentially harmful chemicals such as endocrine disrupting chemicals (EDC), volatile organic compounds (VOCs), heavy metals and pesticides. Studies have shown that long-term exposure to these chemicals, exhibit disruptions in male and female fertility, in both human and animals. [1, 2]
What are VOCs?
Where do they come from?
Why does it matter?
Concentrations of most volatile organic compounds are higher in indoor air than outdoor air
Consequently, exposure of gametes and embryos to such harmful chemicals can have detrimental effects on their growth and development. The environment requirements for gametes and embryos were initially adapted from tissue culture laboratory systems [3]. Better understanding and increased commercial interest for gametes and embryos has led to the recognition of the importance of laboratory air quality as an important factor for the safety of gamete and embryos in IVF clinics.
Several studies (primarily conducted between 1990 – 1998) have shown that poor laboratory conditions in fertility clinics, particularly the air quality can result in impairment of gametes and embryo development thereby reducing the success-rates of such fertility clinics. In fact, studies of air quality in the older ART/IVF laboratory/clinic designs (1990 – 1998) have indicated high concentrations of VOCs (like toluene and iso propyl alcohol) compared to outdoor environment, especially in the incubators. [3, 4]
Most of these IVF clinics/labs had high-efficiency particulate air (HEPA) filters which can remove particulate materials of size ~ 0.3 microns. However, HEPA filters offer limited protection from VOCs. VOC concentration greater than 1 ppm is considered high and can cause direct toxicity to embryos. Embryo development occurs reasonable well at VOC levels of ~ 0.5 ppm, however chances of miscarriage is also very high in such cases. The VOC levels should ideally be zero or at least less than 0.2 ppm. [5]
Carbon activated air filtration (CODA) systems were first implemented in 1997 and provided efficient filtration of VOCs. Clinics which installed CODA systems in addition to HEPA filters reported an increase in high quality embryos, reduction in miscarriages and higher clinical pregnancies. [5]
Regulatory bodies in the European Union and Brazil have specified the air quality requirements in ART laboratories in view of the damaging effects of VOCs and other air contaminants. [6]
Due to the growing amount of evidence suggesting that air contaminants can affect IVF outcome, cleanroom specifications for particulate and microorganism contamination in IVF laboratories have been enforced by European Union laws under Directive 2006/86/EC.
– Esteves and Bento (2016), Asian Journal of Andrology
Heitmann et al (2015), reported a study wherein the mere improvement of air quality in their IVF facility by adopting CODA filters and strategic engineering designs of their lab, yielded nearly 10 % higher live births. No other changes were made to the laboratory equipment, protocols and lab personnel. [7]
Embryo implantation (32.4% versus 24.3%; P < 0.01) and live birth (39.3% versus 31.8%, P < 0.05) were significantly increased in the new facility compared with the old facility.
– Heitmann et al. (2015), Reproductive Biomedicine Online
In another study, Khoudja et al. (2012) studied the influence of the use of a novel-air purification system on IVF outcomes. Their air purification system removes airborne molecular contaminants and chemical air contaminants in addition to VOCs. The results were compared to the outcomes prior to filter change. Few performance indicators are summarized below:
Improvements observed in IVF laboratory performance indicators after changes in air handling systems [5]
It can be clearly inferred from
these studies that improvements in the air quality is fundamental for healthy
embryo development and successful implantation rates, thereby coinciding with
higher live births.
From this discussion, it is therefore imperative that fertility centers have better awareness about the importance of air quality and the factors which can contribute to air contamination inside clinics. The use of certain building materials such as vinyl, paints and fabrics can also contribute to increased VOC level in the clinic environment. New ventures in the IVF domain may unknowingly install vinyl flooring and other such materials for increased aesthetic appeal. This may inadvertently cause elevated levels of vinyl chloride (a known carcinogen) and other VOCs thereby posing a risk to all the stakeholders involved. Understanding and adherence to safety norms in IVF clinics will go a long way in ensuring high success rates of such clinics.
Acronyms
IVF – in-vitro fertilization
ART – Assisted Reproductive Technology
VOC – Volatile Organic Compound
References
[1] Rattan, S., Zhou, C., Chiang, C., Mahalingam, S., Brehm, E., & Flaws, J. A. (2017). Exposure to endocrine disruptors during adulthood: consequences for female fertility. Journal of Endocrinology, 233(3), R109-R129.
[2] Ten, J., Mendiola, J., Torres-Cantero, A. M., Moreno-Grau, J. M., Moreno-Grau, S., Roca, M., … & Bernabeu, R. (2008). Occupational and lifestyle exposures on male infertility: a mini review. The Open Reproductive Science Journal, 1(1), 16-21.
[3] Cohen, J., Gilligan, A., Esposito, W., Schimmel, T., & Dale, B. (1997). Ambient air and its potential effects on conception in vitro. Human reproduction (Oxford, England), 12(8), 1742-1749.
[4] Hall, J., Gilligan, A., Schimmel, T., Cecchi, M., & Cohen, J. (1998). The origin, effects and control of air pollution in laboratories used for human embryo culture. Human reproduction, 13(suppl_4), 146-155.
[5] Khoudja, R. Y., Xu, Y., Li, T., & Zhou, C. (2013). Better IVF outcomes following improvements in laboratory air quality. Journal of assisted reproduction and genetics, 30(1), 69-76.
[6] Esteves, S. C., & Bento, F. C. (2016). Air quality control in the ART laboratory is a major determinant of IVF success. Asian journal of andrology, 18(4), 596.
[7] Heitmann, R. J., Hill, M. J., James, A. N., Schimmel, T., Segars, J. H., Csokmay, J. M., … & Payson, M. D. (2015). Live births achieved via IVF are increased by improvements in air quality and laboratory environment. Reproductive biomedicine online, 31(3), 364-371.
