EDITORIAL BOARD Dr. Sunil K. Jindal Dr. Anshu Jindal

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Vol.19 | Issue No. 128 January 2020

RNI Registration No. UPBIL/2002/8455Postal Registration No. Meerut-131-2018-2020

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Editorial

Supporting and Empowering Sunflowers turn according to the position of the sun. In other words, they “chase the light.”

This facing the sun phenomenon is called HELIOTROPISM

You might already know this, but there is another fact that you probably do not know!

Have you ever wondered what happens on cloudy and rainy days when the sun is completely covered by

clouds? This is an interesting question. Isn't it?

Perhaps you think the sunflower withers or turns its head towards the ground. Is this what crossed your

mind?

Well, that's incorrect! This is what happens?

They turn towards each other to share their energy.

Nature's perfection is amazing. Now let's apply this reflection to our lives. Many people may become low-

spirited, and the most vulnerable ones, sometimes, become depressed.

How about following the example of the beautiful sunflowers i.e."Supporting and empowering each other". Nature has so much to

teach us.

Wishing everyone a "Sun flower" trait of turning towards each other on their cloudy and gloomy days.

Spread goodness...it will come back to you....Start now.

Best wishes to our readers, contributors, friends and well wishers.

We would like to express our appreciation to all the valuable contributors who have helped us to produce this

newsletter that is not only of critical substance but also a pleasure to read. We have tried to express our ideas

and experiences and bring together contributions made by you so as to add value to this growing science. The

aim of this newsletter was to start a paper which could be utilised by the general public as well as a little bit of

knowledge for every Doctor. We would love to distribute Joy, peace and knowledge.With your best wishes, in the month of January our center has 8 ICSI (Intra Cytoplasmic Sperm Injection) & 7 IUI pregnancies.A thousand salutes to this great nation of ours. May it become even more prosperous and great.Happy Republic Day

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N E W S L E T T E RJHAL&IC NEWSLETTER2

Vol.19 | Issue No. 128 January 2020

Dr. Anshu JindalMD, DNB, MNAMS

Improving IVF Success Rate - FAQsWhich category of patients are likely to fail?

v Aged v Polycystic ovarian syndrome v Endometriosis v Mullerian defectsv Uterine factors, fibroids

v Hydrosalpinx v Recurrent miscarriages v Decreased ovarian reserve v Both female & male factor infertility

v Duration of infertility v Obesity v Life style factors- smoking, alcoholh/o previous child birth is a good prognosis factorIs the age of the patient important for success?Advanced maternal age (AMA; >35 year) is associated with a decline in both ovarian reserve and oocyte competence. Female age, duration of infertility & basal FSH are the negative predictors for pregnancy in ART.Any role of type of gonadotrophin used in COS?Does the number of oocytes retrieved have a bearing on IVF success?The number of oocytes retrieved is a key factor for optimizing live birth rates.COS should be tailored to the individual phenotype, maximizing the number of oocyte yield for poor responders and fine tuning for hyper respondersAmong gonadotropin preparations, recombinant FSH gives the highest oocyte yield. Higher FSH bioactivity, which is related to the way the drug is made, filled and delivered.There is a strong association between the number of oocytes retrieved and live birth rates in IVF. The optimum number of oocytes needed to maximize IVF outcomes seems to be about 15. Recombinant gonadotropin preparations are more potent and result in an increased oocyte yield.Oocyte quality vs. quantity Increasing oocyte yield is an opportunity to have more euploid embryos.The goal is to obtain 15 oocytes avoiding OHSS COS should be tailored to the individual phenotype, maximizing the numer of oocyte yield for poor responders and fine-tuning for hyper-responders Is it important to measures progesterone levels on the day of HCG trigger to improve CPR? What we know about progesterone levels in stimulated cyclesMost circulating Progesterone (95%) is produced in the intrafollicular compartment by granulosa cells. Higher serum P are related to more follicles developed (more GCs) and more oocytes retrieved. Treatment with rec-hFSH results in higher P levels than hMG.Rec-hFSH has higher FSH bioactivity (increased GCs and oocyte yield). HMG induces underexpression of genes involved in steroids synthesis. Is there any role of adjuvant therapy prior to IVF treatment to improve success rate including Vit D? Prescribing adjuvants prior to an IVF cycle

v Vitamin D v Myoinositol v Testosterone v DHEAS During an IVF cyclev LH supplementation v GH supplementation

Role of Vitamin D in IVFIn the last decades several studies suggested that vitamin D is involved in the modulation of the reproductive process in women. Vitamin D has also a role in the regulation of sex hormone steroidogenesis. Conclusion: Vitamin D should be adequate before embarking on IVFRole of Myoinositol in IVF

v In light of available evidence of very low quality, we are uncertain whether MI improves live birth rate or clinical pregnancy rate in subfertile women with PCOS undergoing IVF pre-treatment.

v Uncertain whether MI decreases miscarriage rates or multiple pregnancy rates. Showell MG, et al. Cochrane Database Syst Rev. 2018.

Role of Testosterone in IVFTestosterone therapy seems promising to improve the success at IVF in POR patients. Further RCTs with rigorous methodology and inclusion criteria are still mandatory. Testosterone therapy for women with poor ovarian response undergoing IVF: a meta-analysis of randomized controlled trials. Review article Noventa M, et al. J Assist Reprod Genet. 2019.

Role of DHEA in IVFNo significant differences in AFC, ovarian response to a standard low dose of gonadotrophin stimulation and number of oocytes obtained were detected in anticipated normal responders receiving 12 weeks of DHEA prior to IVF treatment.Randomized controlled trial. Yeung T, et al. BJOG. 2016

Role of Growth Hormone in IVFv During ovarian stimulation, GH administration might improve the success rate of in vitro fertilization (IVF) probably through

the beneficial effects of GH on oocyte quality as indicated by a higher number of mature oocytes and embryos. v Still great controversy in the application of GH in IVF. Evidence suggests that GnRH agonist as a final oocyte maturation trigger in fresh autologous cycles is associated with a lower

live birth rate, a lower ongoing pregnancy rate (pregnancy beyond 12 weeks) and a higher rate of early miscarriage (less than 12 weeks)

Dr. Anshu Jindal Moderating a panel discussion on improving IVF success

rate in UPCOG 2019 Varanasi

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Co-treated with gonadotropins and letrozolev Breast cancer patients undergoing IVF to reduce the estrogens levels to increase the number of mature oocytes.v Can be used in normo responders to lower the dose of gonadotropins.v In poor responders to increase the intrafollicular androgen and hence improve oocyte quality. Garcia – Velasco et al 2005 v Same rationale for using DHEA & transdermal testosterone (75mg/day x 30 -120days) for improving infra follicular androgen.Double trigger? v Commonly hCG is the LH surrogate.v GnRH agonist trigger results in luteal phase insufficiency due to lysis of the corpus luteum & poor pregnancy rates.v Double trigger (hCG & GnRH agonist) leads to 25% more mature oocyte retrieval. Griffin et al 2014

More prospective studies required Improving lab AQI – does it help ?Importance of Air quality in lab v High levels of VOC in unfiltered IVF lab air. v Efficient particle & VOC removal.v Mouse embryo development inversely consider with VOC.v Better outcome (PR, IR, miscarriage) in IVF cycles in laboratories with air particle & VOC filtration.Use of time lapse embryoscope – does it help ?v To select the most developmentally competent embryo by automated image acquisition every 5 -20 mintues.v To score embryo's without removing from incubator (no exposure to changes in light, humidity, temperature, pH or gas).Insufficient data to support TLI as a superior methodBlastocyst transfer – does it help ?The blastocyst expansion grade after warming was predictive of successful outcomes independent of the inner cell mass or trophectoderm score. Delayed blastulation and multinucleation were independently associated with lower live-birth rates in frozen cycles. The development of the fair embryos in the culture has a highly positive impact on the pregnancy rate especially in higher responders. This factor should be taken into consideration before deciding how many embryos to transfer. Haas J, et al. J Assist Reprod Genet. 2018.Current evidence shows no superiority of blastocyst compared with cleavage-stage embryo transfer in clinical practice. Additional well-designed RCTs are still needed before robust conclusions can be drawn.Laser hatching – does it help ?In older woman, to overcome the negative effect of zona hardening, LAH could be performed on frozen embryos as a routine strategy before FET in frozen cycles in order to increase the possibility of pregnancy.Freeze all or freeze some ? Favorable when high number of oocytes collected signaling mild OHSS & impairment of endometrial receptivity.When the number of oocytes collected is <15, the freeze all strategy does not appear advantageous. Filpe et al JBRA 2019Is there a role of PGS in improving IVF success ?v Day 5 multicell trophectoderm biopsy has replaced Day 3 single blastomere biopsy.v Genetic testing for PGS has achieved higher accuracy from FISH to aCGH, SNP array, Q-PCR & current next generation seq.PGS may demonstrate abnormal results in more than three quarters of embryos but some of these abnormal embryo's have the potential to give healthy pregnancies.v Embryo mosaicism and trophectoderm sampling technique two major reasons for PGS inaccuracyv 13.4% of embryo's previously diagnosed euploid may be mosaic later.v CPR are similar but higher abortion rates in mosaics.v Multiple trophectoderm biopsy is the norm and biopsy of the inner cell mass is not safe.

Role of Platelet rich plasma (PRP)?Platelet-rich plasma on the endometrial microvasculature seems to be beneficial to patients with refractory endometrium, providing an increase in endometrial receptivity and a consequent increase in implantation rates. As an autologous resource, they are easy to obtain and inexpensive. Recommend it to be included in the different protocols for endometrial preparation, including those in which a natural cycle is preferred.Use of ERA testing ? v Implantation associated gene expression microarray analysis for determining the Window of Implantation (WOI) which is

usually D20-D22 in an ideal 28 day cycle.v Out of phase endometrium thought to play a role in failure 1 in 4 patients undergoing IVF.v Done on day LH surge ± 7 in a natural cycle. v Day 6 of progesterone (HRT cycle).v Results are pre receptive, receptive or post receptive. v Large RCT required for validation & recommending it for

improving IVF success.Performing the ERA test in a mock cycle prior to a FET does not seem to improve the ongoing pregnancy rate in good prognosis

patients. Further large prospective studies are needed to elucidate the role of ERA testing in both good prognosis patients and in patients with recurrent implantation failure.

Factors affecting embryo transfer successv Ease of the procedure v Embryo transfer catheter v Use of ultrasound guidancev Position of embryo in the uterus v Experience of the physician v use of cervical introducerv Presence or absence of blood on the catheter v Removal of the mucus v Bacterial contaminationof the catheterv Retention of embryos in the catheter

For improving implantation

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N E W S L E T T E RJHAL&IC NEWSLETTER4

Vol.19 | Issue No. 128 January 2020

ULTRASOUND –

Dr. Anshu JindalDr. V. Nanda

INFERTILITY –

Dr. Anshu JindalDr. Sunil Jindal

M.D., DNB.M.S., DNB.

OPERATIVE ENDOSCOPY –

Dr. Umang Mittal

ONCOLOGIST –

M.S.

DENTISTRY –

M.D.M.D.

Dr. Sunil JindalDr. Anshu Jindal

M.S., DNB.M.D., DNB.

GASTROENTEROLOGIST –

Dr. Anil Kumar D.M.

NEUROLOGIST –Dr. Vinod Arora D.M.

Dr. Rajeev Jindal BDS

N E W S L E T T E R

Dr. Sunil K. Jindal

Dr. Sunil K. JindalDr. Anshu Jindal

M.S., DNB.

GYNAECOLOGIST –

M.S., DNB.M.S.M.B.B.S, DGO

ORTHOPAEDICS –

ANAESTHETIST –

Dr. Nalini MithalDr. Pranav Gupta

Dr. N. GargDr. Praveen Mittal

PAEDIATRICS –

Dr. Rajiv PrakashDr. Sanjiv Goel

M.D.M.D.

Dr. Anshu JindalDr. Savita AgarwalDr. Suneeta

PHYSICIAN –

Dr. Rakesh AranDr. S.P. SondhiDr. Anil ChauhanDr. V.K. Bindra

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Crossing, Hapur Road, Meerut Editor: Dr. Sunil K. Jindal

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Advanced Laparoscopic, Infertility & Multi speciality Surgical Center

Continue from page 3 SummaryEvidence-based Guidelines1. Effort should be made to avoid ''difficult'' transfers.2. Ultrasound guidance will result in easier transfers with improved outcomes.3. Soft catheters should be used when feasible.Recommendations Based on Expert Opinion

1. Trial transfers allow better preparation for difficult transfers. 2. Cervical mucus should be removed to potentially decrease bacterial contamination and mucus plugging of the catheter. 3. Embryos should be deposited in the midportion of the uterus. 4. Negative pressure should be minimized during withdrawal of the catheter. 5. The procedure should be done in a minimum amount of time.Role of Atosiban?Atosiban may be more appropriate for women undergoing RIF and play only a limited role in improving pregnancy outcomes in the general population of women undergoing IVF. These conclusions should be verified in large and well-designed studies.Oocyte donation? Embryo implantation rates, pregnancy rates, and pregnancy outcomes among women included in oocyte donation programs were shown to be comparable to those of spontaneous or in vitro fertilization (IVF) pregnancies.With oocyte freezing and cryobanks, recipients may have a successful response to oocyte donation, with no need to be on waiting lists, access to a larger number of oocytes from the same donor, and a lesser risk of infectious disease transmission.Live birth rates from oocyte donation in older women are consistent with age of the donor oocyte quality. Increased risk of chromosomal aneuploidy.Decrease in CoQ10 supplementation with aging after the age of 30 years.CoQ10 supplementation restores oocyte mitochondrial activity and decreases oocyte aneuploidy.CoQ10 supplementation for 12-16 weeks in animal models proving to be beneficial. Larger scale clinical studies required in human's.Mitochondrial transfer Autologous mitochondria derived from oocyte precurar cells in the superficial layer of patient's own ovary are injected into patient's oocyte at the time of fertilization.To overcome aged oocytes in poor responders & in recurrent implantation failures. Improving IVF success naturally Any role of acupuncture?Acupuncture does not improve CPR or LBR whether done at the time of OPU or ET.No evidence that it increases the rate of miscarriage.Lack of standardization of the acupuncture points utilized between studies and controls

EL Toukhy T Sankera et al BJOG 2008Summary Cumulative live birth is a key strategy to optimize success in ARTStimulation Protocol and Number of OocytesART FacilitiesTools to Indentify the Most Viable EmbryosCryopreservations Program (Vitrification)