A SECOND CHANCE AT MOTHERHOOD As India gave birth to the world's seven- billionth baby on October 31st 2011, the first thought that crossed my mind was “Why are we always forefront in the population explosion business!” . As I read the article further, I was proud that it happened to be a female child, in a country where infanticide still existed in infamous proportions and in a village that already had a skewed sex ratio. Then my thoughts drifted over to our country's population statistics, male to female birth ratio, disparities among sexes, child labor, poverty line, unemployment, illiteracy- the list was endless. I snapped out of it and shifted focus to the fact that this is a newsletter I was writing and not an article. What is the medical topic of interest that I could share with the numerous doctors and professionals that I mail these to and what is the response I am going to get? Till date, we have received positive feedback for our interesting case presentations and statistics. This time, I have deviated from conventional medical scenarios in assisted reproduction. Our primary service is to cater to those who are childless, then we include those who need a second child and lastly, in the past five years there has been a new trend. Parents that have lost a child or children in natural disasters, illness, road traffic accidents and suicide have been approaching fertility specialists, to get that second chance at motherhood. Majority of them are cases that have undergone family planning after their second or third childbirth. So with failure of a tubal recanalization surgery, or increasing age of the mother being the stumbling blocks, their only means to somehow bear a child in the memory of their lost ones is through assisted reproduction. Mrs. S, 39 years old, stood in front of me, absolutely calm. She is a very good looking woman, who had borne two children, a boy and a girl. The girl now 21 years was, clearly in their social background, of marriageable age. The boy was only 17 when he died in a bike accident two years ago. She had denied him permission to go to a friend's house on his father's bike, which had provoked the youngster to steal the keys and it proved fatal. She never bothered to see his body or listen to any information regarding his death. “I still don't know anything doctor, I simply refused to see or hear any details”. “I only remember him asking me permission to go out and am happy my memory is frozen in time”. Nothing was going to stop her now from having another child which she believes would be his second coming. “I know you can do it doctor, please give me this second chance” she said. Mrs. SL, 30 years old, came to us in March 2011, having lost two beautiful daughters in a road accident in November 2008.They were aged only four and three respectively. She was inconsolable. Two failed attempts of IVF at Kerala had brought her to us. Now pregnant after IVF, she still breaks down at the slightest memories of her daughters. Similarly, Mrs. D, aged 49 years, lost her 24 year old daughter in an accident at Nasik in May 2010. Within 4 months of her death, the couple came seeking treatment. A picture of her daughter adorns her antenatal file, as she gazes anxiously at her scan findings confirming a twin pregnancy. Mrs. JJ, aged 41 years, came to us in February 2006 for treatment after having lost two sons aged 16 and 12 years within a span of 2 years. The elder son had died of an electric shock and the younger one died of a head injury after having been beaten by his school teacher. Tubal recanalization had failed owing to adhesions obscuring the fallopian tubes. She was persistent with her treatment having failed 2 attempts of IVF, followed by a break of 3 years and another failure. She finally conceived twins in her fourth attempt and became a proud mother of a girl and a boy on 22/09/2011. The devastating tsunami of 2004 saw many couples scramble for treatment, especially with hope for tubal recanalization. We had 9 couples of whom 5 conceived and delivered. We had decided to forego the treatment cycle costs for such couples. Mrs. CT, aged 43 years had lost both her son and daughter in a drowning accident in the US in December 2006. She was a staff nurse by profession and came to us in July 2007, few months before the first death anniversary of the children. She conceived in the second attempt with us and delivered twin girls on 2/4/2009 in her hometown of Kerala. Mrs. G S, aged 45 years, came to us exactly a year after her 18 year old son was killed in a hit and run by a lorry on a main road, just across their home in February 2010. She was subsequently operated for multiple fibroids in her uterus and signed up for a donor oocyte programme. There are other issues to be dealt with besides a huge emotional overlay. Most of these women have succumbed to stress and lifestyle related disorders such as Hypertension and Diabetes. In the case of Mrs. G S, she also had partial phrenic nerve palsy which makes it difficult where anesthesia is concerned. Age is also an obvious deterrent where biological conception is concerned, making donor oocyte programme easily acceptable among the couples. Such is the trend where loss of the only child or its sibling brings forth couples to try fertility treatment. What is heart rending is that while they are calm and collected stating what they have come for, we are left fighting tears that threaten to spill, trying to appear just as brave! We have presented the statistics below to show how many such couples have sought help, become pregnant and delivered and the ones undergoing treatment. January 2005 - August 2011 Type of Disasters No of patients No of pregnancies Delivered Ongoing Fetal loss Tsunami 9 5 (56%) 5 (100%) - - Drowning 5 2 (40%) 2 (100%) - - Accident 27 8 (30%) 3 (38%) 3 2 Suicide 2 1 (50%) 1 (100%) - - Illness 14 3 (21%) 2 (67%) 1 - Total no of patients 57 Pregnancies achieved 19 (33.3%) Delivered 13 (68.4%) Ongoing 4 Miscarriages 2 As the numbers increase and as I hold the positive pregnancy test of Mrs. S who lost her teenage son, I am left wondering if it's a privilege or not to enable miracles, surpassing fate or nature's unpredictable ways DR. PRIYA SELVARAJ MD MNAMS MCE Mrs. LD, aged 36 years, married for 11 years came to us for primary infertility on 2/8/2010. She was a known case of polycystic ovarian syndrome and also gave history of two previous early miscarriages in the years 2007 and 2008. She was already on treatment for borderline hypothyroidism since 3 years. Her earlier infertility work up included two diagnostic laparoscopies at two different hospitals for which her reports were not available. Her husband's semen analysis was normal except for mild asthenospermia. She then underwent a diagnostic laparoscopy with us in August 2010 which revealed bilateral patent tubes, save for few adhesions owing to previous procedures. After few unsuccessful attempts at IUI she was finally taken up for an IVF cycle in September 2011. She underwent controlled ovarian hyperstimulation following down regulation with a GnRH analogue and had mild hyperstimulation syndrome. Four embryos in total, including two blastocysts (grade III) were transferred. She tested positive for pregnancy on September 19th with a serum beta HCG value of 106.2 miu/ml. Her first scan to detect a gestational sac was performed on the 38th day, when twin sacs were noted. The weekly scans saw corresponding growth and the fetal heart pulsations were recorded. Owing to our previous experience with Heterotopic pregnancies, the adnexae were also scanned during the first three visits. Unfortunately as she approached the 9th week of gestation she went in for a missed miscarriage. She underwent a D&C on 25th October and was discharged on the same day. On November 5th she developed pain lower abdomen and vomiting and was taken to another tertiary care centre, closer to her home, outside of Chennai, as an emergency. Following her previous history as well as clinical presentation, a suspicion of heterotopic pregnancy was concurred and a pelvic examination was performed. An ultrasound revealed the presence of a mass measuring 7x4cm with heterogenous echogenicity and free fluid in the hepatorenal pouch. Since the patient was hemodynamically stable, she was admitted and observed for a period of two days after which a repeat ultrasound was performed on November 7th. The adnexal mass had reduced to 3x3cm with very minimal free fluid. The patient was then discharged at request from this centre. She presented to us once again on November 10th with pain abdomen and tachycardia and after a confirmatory ultrasound, she was taken up for endoscopic intervention. Hemoperitoneum with a right isthmo-cornual ectopic was observed. A right salphingectomy was performed and abdomen wash was given. She was discharged the next day. Discussion Heterotopic pregnancies occur with an incidence of 1:15000 to 1:30000 in general population and are definitely increased following ART procedures to almost 1:100. The common reasons observed is the increase in tubal factors owing to Pelvic inflammatory disease, endometriosis and factors that general contributed to ovarian pathology or peritubal distortion. Intra procedure reasons cited are increases in length of transfer catheter or in the volume of media in which the embryos are loaded. When a heterotopic pregnancy is diagnosed, the first determinant, if it should be managed conservatively, with injection of potassium chloride transvaginally depends largely on the period of gestation and presentation of the patient. In most cases since the location is isthmo- cornual, it remains undiagnosed until 8th or 9th week of gestation and surgical intervention is needed. But in some instances a conservative approach is feasible. Intervention is almost always the rule and it is either surgical or medical with injection of potassium chloride into the ectopic sac. Expectant management with periodic monitoring of patients blood counts, vitals and size of an adnexal mass may eventually lead to a surgical intervention at the onset of symptoms or a catastrophic event like rupture. Hence this case was presented to not only highlight importance of clinical diagnosis but also the need to implement the right decision of medical versus surgical intervention. Expectant management may not be feasible unless it is detected early enough and can be prolonged till a sign of cardiac activity is noted. But once noted, an intervention would be the rule of the day, in which case the purpose is unserved. DR. PRIYA SELVARAJ MD MNAMS MCE SIGNIFICANCE OF KARYOTYPE IN COUPLES WITH IDIOPATHIC INFERTILITY In an earlier newsletter of ours dated October 2009, we had commented briefly on karyotype polymorphisms in couples presenting with primary infertility. More so, the occurrence of polymorphism in either of the partners or both in cases of idiopathic infertility has been presented. The criteria for assessing karyotype, besides cases of bad obstetric history, consanguinity or known repeated genetic malformations in the abortuses or still borns or live births, has been extended to include chronic failures following ART and idiopathic cases of more than 5 years duration of infertility. The most commonly encountered polymorphisms are a lengthening or shortening of the heterochromatin of the long arm of chromosomes which are designated as 1, 9, 16, qh+. Among the female karyotypes, a lengthening of the heterochromatin on the long arm of chromosome 9 appeared to be the commonest followed by inversions. Other variations include an increase in satellite or stalks on short arm of chromosomes 13, 14, 15, 21, 22 ps+ or pstk+. The men in the idiopathic group were found to have 46 X, Yqh+ as the commonest occurring variant considering that it is mostly associated or seen in men with azoospermia or olizoospermia. An analysis of cases in idiopathic infertility is being presented to note if: These polymorphisms have a role at the cellular kinetic level during gamete cross talk or impending fertilization? It can be used as a predictor for future miscarriages or anomalies if they were to conceive with treatment? It can be a strong basis for counseling regarding need for a gamete change in case they are also poor responders? FROM JAN 2009- JULY 2011 Total no of Idiopathic patients :1459 Total no of female Karyotype :740(50.71%) Total no of Male Karyotype :719(49.28%) FEMALE POLYMORPHISMS (62) Female (740) Male (719) Normal 678 (91.62%) 585 (81.36%) Polymorphisms 62 (8.37%) 133 (18.49%) Polymorphisms Female KT (62) Male KT (133) Pregnancy Outcome Female (4) Pregnancy Outcome Male (7) Normal Variant 26 (46.77) 70(52.63) 1 6 Chromosomal Abnormalities 14(22.58) 24(18.04) 1 - Male factor - 31(23.02) - - Repeated pregnancy loss 13(20.96) 2(1.50) 2 - Gonadal Dysgenesis 6(9.67) 5(3.75) - 1 FEMALE POLYMORPHISMS (62) NORMAL VARIANT(29) No. of cases 46,XX,ADD(22) 2 46,XX,21PS+ 7 46,XX,13PS+ 4 46,XX, DEL(22) (P1 2-PTER) 1 46,XX,16QH+ 2 46, XX, ADD(13) 3 46,XX,14PSTK+ 1 46, XX,INV(9)(P 11;Q13) 5 46,XX,15PS+ 2 46,XX,DEL(13)(P11.1-PTER) 1 46,XX,DEL(9)(Q12) 1 Pregnancy Delivered 1(50) 1(100) CHROMOSOMAL ABNORMALITIES(14) No. of cases Pregnancy Delivered 46,XX,1QH+ 1 1(100) 1(100) Ongoing 46,XX,T(10;16)(Q26;P13.2) 1 46,XX,T(7;17)(P22;Q12)/46,XX 1 46, XX,9QH+ 8 45,XX,DER(13;14)(Q10;Q10) 1 47,XXX 1 46,XX,16QH+ 1 GONADAL DYSGENESIS(6)46,XX,22PS+ 6 RECURRENTABORTIONS(13)46, XX,ADD(15) 8 1(12.5) MOS 47,XXX/46,XX 4 1(25) MOS47,XX,+MAR/46,XX 1 1(100) 1(100) Baby girl G, conceived by Intra cytoplasmic Sperm injection and subsequent blastocyst transfer was delivered by emergency LSCS on June 2011 at 29 weeks FUNGAL SEPSIS IN AN EXTREMELY LOW BIRTH WEIGHT (ELBW) BABY GA with a birth weight of 700g. The indication being a high risk antenatal course of placental dysfunction leading to severe intra-uterine growth retardation, oligohydramnios and absent diastolic flow. The infant cried well at birth, but soon developed severe respiratory distress, for which surfactant and ventilator support were given for 7 days. Subsequently, the baby was extubated and started on nasogastric feeds of expressed breastmilk. In addition, partial parenteral nutrition was given via a central line. The infant had one episode of sepsis and was treated with IV meropenem. Weekly IV fluconazole therapy was given as fungal prophylaxis. On day 40 of life, the infant, who was stable on full feeds and room air, developed shock, severe apneic episodes and bilious vomiting requiring immediate ventilation. X-ray was suggestive of necrotizing enterocolitis. IV Meropenem and fluconazole were restarted. There was thrombocytopenia with clinical bleeds, and plasma and platelet transfusions were administered according to requirements and with diligence. Inotrope support was initiated for shock. The blood culture sent to 2 different labs grew Candida tropicalis: in one lab, the strain was reported as sensitive to amphothericin-B, and in another lab as resistant to amphotericinB. Hence, after discussion with infectious diseases expert, the infant was started on IV micofungin. However, the infant showed severe anaphylactic reactions to this drug, in the form of near-arrest episodes. This was explained to the parents, and amphotericin-B was restarted. After 5 days of amphotericin-B therapy, the blood culture tested negative, IV Meropenem was stopped and the central line was removed. IV Amphotericin-B was continued for 28 days, and the infant gradually improved. Feeds were started after 7 days and gradually advanced. Blood counts and electrolytes were periodically monitored. After 3 weeks, the infant was extubated following adequate weight gain, paladai feeds were started followed by direct breastfeeds. An opthalmologist opinion for retinal screen showed no retinal lesions due to Candida and the ultrasound of the abdomen was normal. USG brain showed no significant bleeds. ECHO showed no vegetations in the heart. The infant was discharged with a weight of 1kg after a course of 3 months in the NICU .This case illustrates the risk factors and management of fungal sepsis in extremely low birth weight babies (ELBW) and also demonstrates the limited evidence about use of new antifungal drugs such as micofungin in such babies. A review of literature about fungal sepsis in ELBW babies follows INCIDENCE OF FUNGAL SEPSIS IN ELBW BABIES Invasive fungal disease : 3-20% Mortality from fungal sepsis: 20-30% CLINICAL AND LABORATORY FEATURE Increase in apnea and/or bradycardia - 63% Increase in oxygen requirement - 56% Increase in assisted ventilation - 52% Lethargy and / or hypotonia - 39% GI symptoms - gastric aspirates, distension, bloody stools -30% Hypotension - 15% Thrombocytopenia:platelet<100000/µL - 84% Immature-total neutrophil ratio of>0.2 - 77% Glucose concentration >140 mg/dL - 13% WBC count >20,000/µL - 12% Metabolic acidosis- 11% Absolute neutrophil count <1500/µL - 3% Elevated C-reactive protein DIAGNOSTIC INVESTIGATIONS Blood culture for fungemia USG abdomen for fungal balls ECHO for vegetations Eye exam for retinal lesions ANTI-FUNGALS 1. Amphotericin-B: Drug of choice: It has good tissue penetration, and resistance is extremely rare Dose: 1.5 mg/ kg IV Q24H for 25 to 30 days No test dose needed in neonates Infusion over 2-6 hours, protected from light Toxicity: Decrease Glomerula Filtration Rate (GFR), injures renal tubules RISK FACTORS FOR FUNGAL SEPSIS IN ELBW BABIES 2. Fluconazole Good tissue and CNS penetration Dose : 6mg/ kg Q24h to 72h IV Side-effect: Reversible derangement of LFT Concern about resistance, especially to Candida non-albicans 3. Liposomal Amphotericin-B Accumulates in MPS, to higher dose is needed Dose : 5mg/ kg over 2 hours daily Less nephrotoxic Expensive Indian Liposomal Amphotericin B derived from neutral lipids L-Amp-LRC-1: economical 4. Echinocandins Caspofungin Micafungin, anidulafungin Dose : 1-2 mg/kg/ dose IV Useful in refractory candidiasis 5. Other therapies Supportive care Stopping antibiotics Removing central lines DR. DEEPA HARIHARAN MBBS, A.B (Paeds/Neo) (USA), FAAP Neonatologist, G G Hospital. DO WHAT CAN’T BE DONE…. DO what can’t be DONE… Do they say then find the way to do it, can't be done? Anything that is considered impossible is an opportunity waiting to be harvested. Just imagine the incredible power of being able to say "I can" when everyone else is saying " I can't” "I can't" usually means "I won't". be the person who will. It is easy to say "NO" to avoid the challenge and the effort. Success comes to those who say "YES" and then set about to make it happen. Constant complaints and Excuses will keep you imprisoned in a tedius world of mediocrity. Yet what is impossible for others, does not have to be for you. Welcome the challenges. Take the initiative. Feel the satisfaction of accomplishing that which has never before been attempted. Look for things Which can't or won't be done. Be the one who makes them happen, and reap their enormous value. - Ralph Marston Dr. Priya Selvaraj MD MNAMS MCE OUR ART BABES Name : N.Sugunamayi Extra curricular Activities : Bharathanatiyam. She has completed her arangetram. has also won in all school dance programms DOB & Age : 21/08/1995, 16 YRS Conception : IVF ET Class : 12th STD Ambition : To become an I.A.S officer or Charterd Acconuntant Name : Ananya Ramesh DOB & Age : 112/2008 & 3 YRS Conception : IVF ET She speaks english fluently and is very good in singing DOB & Age : 03/12/2007, 4 YRS Conception : IVF ET Extremely proactive and energetic twins TWIN 1 : P.Siva Kamalam TWIN 2 : P.Siva Priyam Name : Mohana Sundari DOB & Age : 06/01/1998, 13 YRS Conception : IVF ET Class : 8th STD Ambition : To become a Doctor Sports (Gold medalist in running & long jump) singing, dancing and drwing MONTHLY IUI PREGNANCIES ( JAN 2011 - OCT 2011) OVERALL MONTHLY PREGNANCIES ( JAN 2011 – OCT 2011) TOTAL No. OF PREGNANCIES/ MONTHLY (JANUARY 2009 JUNE 2009) **(Easy Transfers and good quality of embryos) MONTHLY PREGNANCIES ( JAN 2011 - OCT 2011) Art IUI Natural * 42 12 19 56 10 17 45 16 14 50 20 11 32 8 10 44 19 7 46 20 8 41 21 17 56 21 17 44 18 10 456 192 150 OVERALL PREGNANCIES ( JAN 2011 – OCT 2011) *Following medical and surgical management ART STATISTICS (JAN 2011 - OCT 2011) PROCEDURES NO OF CASES PREGNANCIES PREG.RATE (% ) IUI (OWN / DONAR) 1730 207 11.96 IVF ET 2 0 0 ICSI ET 186 59 31.7 IVM ICSI ET 4 0 0 BT 5 3 60 IVF + ICSI ET 1 0 0 FROZEN ICSI ET 34 13 38.23 FROZEN IVF + ICSI ET 4 4 25 281 133 52.66 139 81 58.27 28 12 42.85 OWN 39 12 30.76 DONOR 24 9 37.5 GENERAL FROZEN EMBRYOS SEQUENTIAL TRANSFER ( OWN / DONOR ) DAY 2 AND DAY 5 TRANSFER (OWN) DAY 2 AND 5 TRANSFER ( DONAR) DAY 2 AND 5 TRANSFER (OWN / DONAR) RUPTURE ET DONOR OOCYTE PROGRAMME ( DOP ) IVF ET 3 0 0 ICSI ET 64 18 28.13 OOCYTE THAWING HRT ICSI ET 1 0 0 5 0 0 1 1 100 16 3 18.75 5 3 60 35 11 31.42 11 2 18.18 BT DUAL DONOR EMBRYO PROGRAMME IVF ET ICSI ET FROZEN DET BT Total Number of pregnancies achieved Total Number of patients delivered by ART Total Number of babies delivered by ART Total Number of ongoing pregnancies Total Number of Fetal wastages Lost in follow up : 4431 : 2460 : 3360 : 210 : 1715 : 46
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