pISSN NO. 2277 - 8845 eISSN NO. 2278 - 2044 Volume - 1, Number - 3, July - September 2012 Chettinad Health City MEDICAL JOURNAL In this issue Size of Follicle and Oocyte Maturation Status in an Assisted Reproductive Technology Programme Review Articles on Obstructive Sleep Apnoea Nobel Prize in Medicine 2012 Interview with Dr. V Shanta Edward Jenner - The Father of Vaccination www.chettinaduniversity.com/journal All rights are reserved Chettinad Academy of Research and Education (CARE) Chettinad Health City Medical Journal is published by the Chettinad Academy Dr. M.A.M.Ramaswamy Shri M.A.M.R. Muthiah of Research and Education. Chancellor - CARE Trustee - CARE Apart from the fair dealing for the Dr. V. Raji Mr. SPK. Chidambaram purposes of research or private study, Vice Chancellor - CARE Registrar - CARE or criticism or review, no part of the publication can be reproduced, stored, or transmitted in any form or by any Editorial Advisors means without the prior permission. Dr. V. Raji Chettinad Health City Medical Journal Dr. K.Ravindran and /or its publisher cannot be held Dr. R.M.Pitchappan responsible for errors or for any consequences arising from the use of Dr. P. Rajesh the information contained in this Mrs. L. Lakshmi journal. The appearance of advertising or product information in the various sections in the journal does not constitute an endorsement or approval Chief Editor by the journal and / or its publisher of the quality or the value of the said Dr. N. Pandiyan product or of claims made for it by its manufacturer. Editors Associate Editors EDITORIAL OFFICE Dr. K. Ramesh Rao Dr. D. C. Mathangi Dr. N. Pandiyan Dr. R. Murugesan Dr. V. Anitha Chief Consultant, IVF Dr. Pradeep G. Nayar Dr. Thilaka Muthiah Chettinad Health City Dr. K. Senthil Kumar Rajiv Gandhi Salai, (OMR, Chennai), Kelambakkam, Kanchipuram Dist Tamil Nadu - 603 103 India Section Editors T. +91 (0)44 4742 8300 F. +91 (0)44 4741 3343 Dr. Ashok Palaniappan Dr. A.S. Natarajan Email: Dr. John Paul Evangel Judson Dr. R. Pandurangan [email protected] Dr. R. Ganesan Dr. D. Rajasekaran Dr. M. Jeya Dr. Ramnath Shyamala Dr. S. B. Jothi Ramalingam Dr. R. Ravi Kumar Dr. Lailu Mathews Dr. A. Ruckmani PUBLISHED BY Dr. E. Malligai Dr. B. Srinivasan Chettinad Academy of Research and Dr. C. Manohar Dr. M. S. Srinivasan Education D r. R. Mu r a l i Dr.S. Thayumanavan Dr. Nagajothi Dr. Vasantha N Subbiah Dr. M. Narayana Reddy WEBSITE www.chettinaduniversity.com/journal IT Support & Design Legal Support Mr. S. M. Michael Mr. Balaji Mr. Ramesh Palaniappan All disputes within the jurisdiction of the Madras High Court only Mr. S. T. Manigandan (Designs) pISSN NO. 2277 - 8845 eISSN NO. 2278 - 2044 Chettinad Health City MEDICAL JOURNAL Contents Editorial N Pandiyan Original Article 1. Size Of Follicle and Oocyte Maturation Status in an Assisted Reproductive 82 Technology Programme Gayathiri Ganesan, Savitha, Radha Pandiyan Review Articles 2. Obstructive Sleep Apnoea: Prevalence, Consequences, Pathophysiology 83 and Treatment Kelly Shepherd & Peter Eastwood 3. Obstructive Sleep Apnoea in Adults - The ENT Perspective 99 S B Jothiramalingam, S K Jha, P Thirunavukarasu, L Jagadeesh Marthandam 4. Surgical Management of Sleep Apnoea 104 Rajesh P 5. Anaesthetic Considerations in an Obese Patient with Obstructive 108 Sleep Apnoea Balachandran S, Hari Prasad NVG, Anand K 6. Obstructive Sleep Apnoea and Cardiovascular Disease 117 Ganesh N 7. Overlap Syndrome – the Coexistence of Sleep Disordered Breathing (SDB) 120 and Chronic Obstructive Pulmonary Disease (COPD) Subramanian S, Apar Jindal 124 8. Obstructive Sleep Apnoea in Children Srinivasan K, Jaishree Vasudevan Case Reports 9. Dental Implants with Simultaneous Guided Bone Regeneration 128 Anitha V, Shivakumar V, Shanmugam M, Saravanakumar R 10. Prosthodontic Correction of Midline Diastema 131 Sridharan R, Saritha M K 11. Nobel Prize in Medicine 2012 133 Ramesh Rao K From the Pages of History 134 12. Edward Jenner - The Father of Vaccination Pitchappan R M Dialogue with the Stalwart 13. Interview with Dr. V Shanta Volume 1, Number 3 Editorial OSA gets compounded with other respiratory ailments and most interesting of it is the COPD, called the Vanakkam. This issue of the journal, besides the usual overlap syndrome described in the 6th article. sections, carries a special section on “Obstructive sleep apnoea”. “An interview with a stalwart “highlights the Adults with sleep apnoea have increased day time meeting with Prof. V. Shantha, gynaecologist and sleepiness; however children with sleep apnoea are oncologist, Magsaysay awardee and a doyen among hyperactive. OSA also affects cognition. Hence identi- cancer specialists in India. fication and treatment of this condition should start early. The 7th article details sleep apnoea from a peadi- atricians perspective. In assisted reproduction, at what size to trigger ovula- tion is often a debatable issue. An original article on Sleep apnoea has also been identified in the west as one “Follicular size and oocyte’s maturity” outlines the of the main causes for vehicular accidents and increased author’s observations in an Assisted Reproduction economic burden. We hope this issue of CHC Medical programme. Journal, updates and enhances your knowledge on sleep apnoea. Obstructive sleep apnoea is a multi systemic disorder with impact on several bodily functions. Two case reports from the Dental College discuss the problem of Diastema and Dental Implants. Several review articles bring out the patho physiology and management of obstructive sleep apnoea. This Vaccination has been one of the greatest advances in section was coordinated and edited by Prof. Mathangi modern medicine which has helped save millions of Chandrasekhar. lives. An article from the pages of history outlines the discovery of small pox vaccine. The usual column Medi- cal Update suggests taking curry to avoid metastasis and Sleep is probably the most important voluntary body has many more useful information from all over the function which has an impact on almost every other world. Hope you enjoy going through the journal and system in the body. Lack of quality sleep is a universal give us your valuable feedback. phenomenon. Almost everyone is affected at some time or other. However, chronic lack of sleep is common among many of the upwardly mobile group of technocrats, bureaucrats, businessmen, professionals, politicians and their like. Many of these professionals have excessive day time sleepiness, lack of freshness, morning headaches, which affect their performance at Dr. Mathangi Chandrasekhar the work place as well as personal life. All these put Section Editor : Chettinad Health City Medical Journal together with apnoea spells during sleep results in a E-mail : [email protected] disorder called obstructive sleep apnoea (OSA). Our current day erratic lifestyle, highly stressed work environment, sedentary life style leading to obesity, further compounds the occurrence of obstructive sleep apnoea. In addition, the craniofacial anatomy with narrow airway among Asians further increases the prevalence of sleep apnoea among Indians. Dr. N. Pandiyan Though we have significant publication in this area Chief Editor : Chettinad Health City Medical Journal from the west, there is dearth of information from our E-mail : [email protected] country. There is a lack of awareness of these disorders among physicians as well as public. Hence this issue concentrates on the various aspects of sleep apnoea. The 1st article reviews the international guidelines and status on the diagnosis, pathophysiology and treatment of OSA as well as several of the co morbidities commonly associated with the disorder. The 2nd article deals with the treatment aspects from an ENT perspective and the 3rd Dental perspective. The 4th article addresses this disorder in detail from an anaesthetic perspective. Untreated OSA can lead to high blood pressure, uncontrolled diabetes, heart attack, strokes, even heart failure. The cardiovascular morbidity and OSA is explained in the 5th article. 82 Chettinad Health City Medical Journal Original Article Size Of Follicle and Oocyte Maturation Status in an Assisted Reproductive Technology Programme Dr. Gayathiri Ganesan*, Dr. Savitha**, Dr. Radha Pandiyan*** *Junior Consultant, Chettinad Super Speciality Hospital (CSSH), **Clinical Embryologist (CSSH), ***Senior Consultant Department of Reproductive Medicine (CSSH) Dr. Gayathiri Ganesan did her undergraduation and postgraduation (M.S (OBGY)) in Sri Ramachandra Medical College. Further she did fellowship in Andrology and Reproductive Medicine from Chettinad Hospital and Research Institute. She is currently a Junior Consultant in Department of Reproductive Medicine in Chettinad Super Speciality hospital. Corresponding author - Dr. Gayathiri Ganesan ([email protected]) Abstract Background : To asses the correlation between follicular size and oocyte maturation status in assisted reproductive technology programs. Method : It was a prospective study done from September 2011 to May 2012 in the Department of Reproductive Medi- cine at a tertiary care hospital. Sixty patients undergoing assisted reproductive cycles either with agonist or antagonist protocol were included in this study. Follicles were subdivided into four arbitary groups according to their mean two dimension size, >21 mm, 16-20 mm, 12-15 mm and <12 mm. Microscopic examination of the follicular aspirates were performed by the embryologist. Findings : If follicle size > 21 mm , there was 85% chance of retrieving an MII oocyte; when the size was between 16 – 20 mm,the chance of retrieval was 87%. In 12 – 16 mm group, it was 80% and in the follicles <12mm it was 55%. The level of significance was calculated between each group ( with respect to MII oocytes). Between the first three groups, p value was not significant. When the larger sized follicles were compared with < 12 mm group, p = 0.000, which was statistically significant (p< 0.05). Conclusion : It is better to trigger with HCG when the lead follicle is between 16 – 20 mm rather than waiting till > 21 mm, as this saves time and money for the patient. Small follicles of size < 12 mm also yielded MII oocytes, hence it is worthwhile aspirating small follicles also. Funding : Nil Key Words : Follicular size, Oocyte quality, Oocyte maturity, Controlled ovarian hyperstimulation Chettinad Health City Medical Journal 2012; 1(3): 83 - 87 Introduction Follicle size is associated with oocyte development in most species and this may indicate that a specific size is necessary to initiate the molecular cascade of normal nuclear and cytoplasmic maturation.1,2 The development and maturation of a follicle undergo a series of events in the natural menstrual cycle. . Recruitment of group of follicles – The initial recruitment and growth of primodial follicles are not under the control of any hormone. After certain stage (2 – 5 mm in size) the growth and differentiation are under the control of FSH. Unless the follicles are rescued by FSH at this 83 stage, they undergo atresia. Fig. 1 Original Article Size Of Follicle and Oocyte Maturation Status in an Assisted Reproductive Volume 1, Number 3 Technology Programme . Selection of Dominant follicle and maturation – an oocyte is independent of its follicular size origin5 . There is accelerated growth of all the components of the follicles. As early as day 5-7, one of the It should be noted that embryo competence is most follicle out of so many in the cohort becomes likely due to the quality of the originating gametes . dominant and undergoes further maturation. The Therefore, the morphological appearance of the oocyte one with maximum receptors for FSH, becomes is likely to contribute to the development potential of the dominant follicle (Graafian follicle). The rest the subsequent embryo. become atretic by day 8. . Ovulation – The cumulus becomes detached from Classification of oocyte maturity6 the wall so that the ovum with the surrounding cells float freely in the liquor folliculi. The oocyte Normal oocyte completes first meiotic division with extrusion of the first polar body which is pushed to the perivi- 1. Metaphase II telline space. The follicular wall near the ovarian A mature or a good metaphase II oocyte is defined as an surface becomes thinner. The cumulus escapes oocyte with clear, moderately granular cytoplasm, out of the follicle by a slow oozing process along small perivitelline space and clear to colourless zona with varying amount of follicular fluid. pellicuda7 . First polar body is round or ovoid with . smooth surface8,9,10. Cumulous cells are fully radiating Corpus Luteum formation – After ovulation, the and easily stretchable. ruptured Graafian follicle develops into corpus luteum. The colour is yellow due to the presence 2 .GV (Germinal Vesicle): of lipids. . It is an immature oocyte where the cumulous cells are Regression – On day 22-23 of cycle, retrogression tightly packed. The nucleus is large. It is preincubated occurs. The corpus luteum becomes corpus before insemination. albicans. 3.Metaphase – I Controlled ovarian hyperstimulation is not critical to assisted reproduction though soft and mild stimulation It is an immature oocyte which has tightly packed cumu- regimes have been advocated to closely mimic physi- lus cells. There is no nucleus or polar body. ological events. Still many prefer the controlled ovarian hyperstimulation to augment the number of oocytes 4.Very mature : retrieved and embryos generated. Of these, only a small portion will be competent for fertilization and This oocyte is pale.It has little corona cell. development into viable embryos. Understanding the process of selection, follicular growth and ovulation has 5.Luteinized: guided the development of this important component of treatment. The medications, designed to override This oocyte is very pale and difficult to find. Cumulus the selection of a single dominant follicle, drive multi- cell is broken down and becomes a gelatinous mass. ple antral follicles into the growth phase. These follicles There is low probability of fertilization. It is insemi- grow at different rates, and management is guided by nated with little delay. their size rather than their competence. The adminis- tration of Human Chorionic Gonodotrophin, in 6.Atretic: mimicking the endogenous luteinizing hormone [LH] It is very dark oocyte with fragmented cumulus cells. It surge, is the final event that determines the follicular has a lace like appearance and is difficult to identify. maturity and developmental competence. The timing of its administration is typically guided by the size of the lead follicle or lead follicular cohort 3. Materials and Methods The treatment is therefore based on an assumption that The present study is a prospective study conducted in follicular size predicts the maturity of the oocyte. The the Department of Reproductive Medicine at a tertiary assumption is based on limited studies using different care hospital from September 2011 to May 2012. 60 models in animals. Yet the available data is conflicting, patients undergoing assisted reproductive cycles either and although several human studies have suggested with agonist or antagonist protocol were included in oocytes derived from larger follicles outperform [in this study. Individuals were serially monitored with terms of fertilization and embryo quality] oocytes transvaginal ultrasound from day 5 onwards of stimula- originating from smaller follicles, the correlation of tion and all follicles were measured in two dimensions. oocyte competence with follicular size, after controlled The decision to administer HCG was based on the lead ovarian stimulation, has not been well characterized. follicular cohort, usually with atleast 3 follicles measur- For instance, while some have suggested the decreas- ing 20mm in diameter and also an endometrial ing fertilization rate and embryo quality observed with thickness of 8 mm onwards. Follicular size measure- oocytes originating from smaller follicles can be ments were made serially and on the day of HCG overcome with intracytoplasmic sperm injection trigger. A transvaginal ultrasound guided follicular [ICSI]4. Others have suggested normal fertilization of aspiration was conducted 35 hours after hCG adminis- 84 tration. Original Article Size Of Follicle and Oocyte Maturation Status in an Assisted Reproductive Volume 1, Number 3 Technology Programme Normal Oocytes Metaphase lI Fig 2: M II Oocyte Before Denudation Fig 3: M II Oocyte After Denudation Germinal vesicle Fig 4: G V Before Denudation Fig 5: G V After Denudation METAPHASE I Fig 6: MlI Oocyte Before Denudation Fig 7: M I Oocyte After Denudation 85 Original Article Size Of Follicle and Oocyte Maturation Status in an Assisted Reproductive Volume 1, Number 3 Technology Programme Fig 8: Very Mature Oocyte Fig 9: Luteinised Oocyte Results Table 1 Oocyte Maturity and Size SIZE(mm) OOCYTE MATURITY TOTAL (N=489) MII M1 GV ABNORMAL >21 110(85%) 5(3.8%) 9(6.9%) 6(4.3%) 130 16-20 179(87%) 8(3.9%) 6(2.9%) 13(6.2%) 206 12-15 71(80%) 10(11.2%) 6(6.7%) 2(2.1%) 89 <12 35(55%) 13(20%) 11(17.2%) 5(7.8%) 64 study. In follicle size > 21 mm , there was an 85% chance of retrieving MII oocyte. When the size was between 16 – 20 mm,the chance of retrieval was 87%. In 12 – 16 Fig 10: Atretic Oocyte mm group, it was 80% and in the follicles < 12 mm it was 55%. The level of significance was calculated between each group (with respect to MII oocytes). Follicles were subdivided into four groups according to Between the first 3 groups, p value was not significant. their mean two dimension size, >21 mm, 16-20 mm, When the larger size follicles were compared with < 12 12-15 mm and <12 mm. All follicles were aspirated under mm group, p = 0.000, which was statistically significant (p< 0.05). transvaginal ultrasound guidance with a double lumen 17G oocyte pickup needle (Swemed) at 100 mmHg Discussion pressure. Flushing of aspirated follicles was performed with flushing medium phospate buffered saline (PBS- In the study by Mitchell et al3, they grouped the size of SAGE) once or twice if oocyte was not obtained in the follicles into arbitrary five groups, > 18 mm, 16-18 initial aspirate. Volume of the aspirate was found to be mm,13-15 mm,10-12 mm and < 10 mm. The percentage >3 ml in larger follicles, around 2 ml in the intermediate of MII oocytes from each group were 90%, 79%, 73% follicles and < 1 ml in small follicles ,53% and 47.6% respectively. The effect was a mono- tonic decrease in the odds of obtaining a mature oocyte Microscopic examination of the follicular aspirates with decrease in the follicle size group. were performed by the same embryologist. Once the oocytes were identified, they were collected and kept In a study done by Ectors et al11 , they grouped the in the four well dishes with G-IVF media. Aspirates aspirated follicular fluid volume into three groups, < were screened individually and the maturity of oocytes 2ml as small (size < 16 mm), 2-6 ml as medium (16 – 23 were noted from each size of the follicle. Further study mm) and >6 ml as large (>23 mm). Higher percentage of the development of individual oocyte was not possi- of oocytes were collected from the medium size ble due to group culture. follicles. 50.8% were MII oocytes, which were collected from medium sized follicles as compared to 86 Table 1 shows the association between the size of the 24.7% and 24.5% from small and large follicles respec- follicles and maturity of the oocytes obtained in the tively. Original Article Size Of Follicle and Oocyte Maturation Status in an Assisted Reproductive Volume 1, Number 3 Technology Programme They further concluded that good embryos were found 5) Salha O, Nugent D, Doda T, Kaufmann S, et al. in medium sized group. In the present study, a good The relationship between follicular fluid aspirate yield of follicles were achieved from large follicles but volume and oocyte maturity in IVF cycles. Hum small follicles also yielded mature oocytes. Reprod 1995;13:1901-6. In the present study. the chance of retrieving a MII 6) Brian Dale and Kay Elder, Text book of In Vitro oocyte from follicle size > 21 mm was 85%. When the Fertilization, 2nd Edition, 1997. size was between 16 – 20 mm,the chance of retrieval was 87%. In 12 – 16 mm group, it was 80% and in the 7) Veeck LL. Oocyte assessment and biological follicle < 12mm it was 55%. The level of significance performance. Ann NY Acad Sci 1988;541:259-74. was calculated between each group ( with respect to MII oocytes). Between the first 3 groups, p value was 8) Balaban B, Uramn B et al. Effect of oocyte not significant. When the larger size follicles were morphology on embryo development and compared with < 12 mm group, p = 0.000, which was implantation. Reprod Biomed Online statistically significant (p< 0.05). 2006;12:608-15. In view of the above findings, it is impossible to lay 9) De Sutter P, Dozortzev D, Quain C, et al. Oocyte down a treatment scheme. We conclude that it is advis- morphology does not correlate with fertilization able to aspirate all ultrasonically visible follicles rate and embryo quality after ICSI. Hum Reprod (regardless of size) at the time of oocyte retrieval in 1996;11:595-7. order to achieve the maximum benefit from each cycle. Since each patient in every cycle responds differently to 10) Ebner T, Yaman C, et al. Prognostic value of first ovarian stimulation, it is impossible to lay down a polar body morphology on fertilization rate and uniform treatment scheme applicable to everyone. It is embryo quality in ICSI. Hum Reprod necessary to arrange the ovarian stimulation as 2000;15:427-30. individually as possible, according to patient’s age, cause and the way they respond to stimulation protocol, 11) Ectors FJ, Vanderzwalmen P, Van Hoeck J, Nigs aiming at a continuous multifollicular oocyte develop- M,et el. Relationship of human follicular diameter ment. The degree of this maturation is indicated by with oocyte fertilization and development after follicular growth and development and is assessed most IVF or ICSI. Hum Reprod 1998;12:2002-5. readily by transvaginal ultrasonography. Traditionally, oocyte retrieval is based on ultrasonographic measure- ment of the leading follicle, but if smaller follicles have oocytes of equal developmental potential, HCG could be administered earlier at a follicular size of about 16-18 mm to save time and expense for the patient. Acknowledgements : The author wishes to thank Dr. N.Pandiyan for suggesting this topic for research and Dr.Ramesh Raja, Dr. Kavitha, Dr. Krithika Devi and the paramedical staff at the Reproductive Medicine Department for their support. References 1) Trounson A., Anderiesz C, Jones G. Maturation of human oocytes in vitro and their developmental competence. Reproduction 2001;12:51-75. 2) Xuerong Wen, Amanda J, Tozer. Follicular fluid levels of Inhibin A, Inhibin B and activin A levels reflect changes in follicular size but are not independent markers for oocytes ability to fertilize. Fertil Steril 2006;85(6):1723-29 3) Mitchell P Rosen, Shehua Shen, Antony T, Dobson. A qualitative assessment of follicle size on oocyte development competence. Fertil Steril 2008;90:684-90. 4) Bergh C, Borden H, Lundin K,et al. Comparison of fertilization, cleavage and pregnancy rates of oocytes from large and small follicles. Hum Reprod 1998;13:1912-15. 87