Dr Nandita Palshe etkar
Vice President Elect Librarian Hon. Secretary Managing Committee
FOGSI (2011) MOGS AMOGS. IAGE & IS SAR .
Member
Member
National Guidelines G for Accreditation, on & Regulation of ART Supervisio Clinics in India (2006-2007).
Felicitated by Mayor of Mumbai as Wo omen Achiever -2010. Recipient of HexWorld Newsmakers Achievers A Award For Best Doctor-2010.
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
•Professor in Obstetrics & Gynecology at D.Y. Patil Medical College,
Navi Mumbai Mumbai.
•Teacher for super specialty degree, FNB Reproductive Medicine, •Practicing Infertility for the last 15 5 years.
Director at five BLOOM IVF centers –
•Lilavati Hospital IVF Centre, Mumb bai •D.Y.Patil Bloom IVF Fertility Centre e, Navi Mumbai •Fortis F i L La F Femme IVF C Centre, N New Delhi D lhi •Fortis Bloom IVF Centre, Chandiga arh •Fortis Hiranandani IVF Centre, Nav vi Mumbai.
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Male Inf fertility y
Management strat tegies
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Male Factor F
Incidence 50%
30% severe male fa actor 20% subfertility
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Causes of ma ale infertility y
Other Obstruction O Tumor Immunologic Systemic Malformation Cryptorchidism Hypogonadism Infection V i Varicocele l Idiopathic
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Algor rithm
Oligospermia
Mild
5 10 million count 5-10 Emperical Mgmnt R/o Varicoel & incomplete block in vas
Severe e
< 3-5 mill lion ICSI
IMS SI PIC CSI
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Specific p Medical Treatment
Oligospermia g p with ↓ed te estosterone & normal LH
CC
Hypogonadotrophic hypo ogonadism
HCG + FSH
Hyperprolactinemia
MRI – Bromocriptine
Congenital adrenal hyperplasia
Glucocorticoids
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
S Specific f Medic d cal l Treatment
Pyospermia Frequent ejaculation n, Doxycycline, NSAID Retrograde ejaculation Pseudoephedrine / IUI I / ICSI
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Idiopathic p Ma ale Infertility y
Many men presenting with infertility are found to
have idiopathic oligo-astheno-teratozoospermia (OAT) syndrome. for OAT, is found in 40-75% of infertile men.
No demonstrable cause of male infertility, except Most common pathological cause of Idiopathic
infertility is – free radical induced damage to the sperm.
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Reactive Oxygen Species is one of the
major contributors to male Infertility & cause damage to the e sperm
Mechanism of ROS S-induced sperm
dysfunction: f
– Peroxidation of spe erm membrane lipids
(accumulation of lipid peroxides) – ATP depletion – Oxidation of protei ins/SH-groups – DNA oxidation/frag gmentation
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Mitochondr rial Medicine
A term to convey the mitochondria as a target for therapy.* Mitochondrial DNA (mtDNA) en ncodes essential subunits of the
respiratory chain critical for energy production.**
*ACAD EMERG med . September 2003 **J i intern t med d 1999; 1999
Mitochondrial DNA (mtDNA) has a poor p repair mechanism and a many-fold
higher incidence of mutations compared to nuclear DNA. DNA
Yq microdeletions lead to ch hanges in the fertility potentials.
-Kumar R -Kumar R. India International Journal of Urology Urology. 2010
Some of the mitochondrial problems can be overcome through administration
of high g doses of coenzymeQ y Q10, the e critical electron carrier in the electron transport chain (ETC).
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
CYTOPLASM
OUTER MITOCHONDRIAL MEMBRANE
INTERMEMBRANE SPACE
H+ H+ H+ H+
H+H+H+H+ H+ H+ H+ H+
I
2NAD.4H
e Q.4H
2NAD
Q II -
Q Q H Q.4H Q.4H
III
H+
c IV
e e
eO-2
V
2H+
2FAD.4H 2FAD
O2
O2
MITOCHONDRIAL MATRIX
O2
2
O2
O2
H2O
energy p ph
ADP
2
ATP
O2 O 2 Vice-President O Dr Nandita Palshetkar , First FOGSI 2011 2O , Lilavati Hospital Mumbai
14
Mitochondria - so ource of oxidative stre ess
Mitochondrial toc o d a p proton oto le e eak ca ea can accou account t for o
almost 20% of oxygen consumption.* The modulation of p prot ton leak appears pp as a possible and attractive target to control oxidative stress with im mplications for male gametogenesis.* CoQ10, the critical elect tron carrier, can capture the h electrons l easily il and d avoid id the h oxidative id i stress.
*Cell Biochemistry and Function. Volum me 28, Issue 3, pages 224–231, April 2010
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
CoQ10 Improves sperm count and motility i idi in idiopathic thi oligoa li sthenozoospermia. th i
. Safarinejad MR ,J Urol. 2009 Jul Jha AK, Arora RP Ind J Urology. 2002 Balercia G, et al. Fertil Steril. S 2009 & May Abdul Rasheed OF, et al. a Saudi Med J. 2010. Balercia G, et al 2010. J Endocrinol In nvest. 2009 Jul
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
CoQ10: Blood Leve els & Implications p
Deficiency Opimal < 0.5 mcg/ml. 1 mcg/ml. / l > 2 mcg/ml mcg/ml. > 3.5 mcg/ml (achievable
Absorption p - better when given with food. 100 mg g CoQ10 increases plasma levels to ~ 2 mcg/ml at steady state. 90% of steady state plasma level is achieved in 4 days. Plasma half-life ~ 33.9 h.
Therapeutic Best Effects
with 300-600 mg/day dose of CoQ10).
Langsjoen PH & Langsjoen AM. Asi ia Pacific Heart J 1998; 7(3): 160-168.
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Medical treatment t
Coenzyme Q10 to impro ove electron transport chain
function, and thereby th he energy production in the mitochondria of the sperm m Selenium to increase antioxidant defense through raising g the levels of g glutat thione p peroxidase Lycopene to preserve the e structure of the mid-piece of the spermatozoa The combination is likely to be more beneficial f to treat male infertility rela ated to poor motility of the sperms. p DHA& EPA enhances spe erm flexibility (it contains 6 double bonds). 95% of f fatty acid in the sperm membrane b i DHA! is
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Clinical management should be expedited considering c
Age A of f the h women Cost effectiveness
Presence of multi-fac ctorial infertility
Duran et al, Hum Reprod, Aug 2002
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Gynaecol y ogist g ART
IU UI IC CSI IM MSI PIC CSI
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Mild OAT
Medical Therapy 3 3-6 6 months 3-4 IUI cycles if coun nt improves.
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Severe OAT <5 mill Azoospermias p
ICSI - Ind dications
Failed fertilization in IVF Preimplantation gen netic diagnosis Immunological facto ors Oncology: frozen th haw sperms may be
grossly impaired Ejaculatory dysfunction Paraplegic males: TESE with ICSI
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Protocol for ICSI
Ovarian st timulation l Monitoring g cycle l Induction d ovulation l Oocyte O ret trieval l
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Scanning Oocytes
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 , Lilavati Hospital Mumbai
Embryo T Transfer
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Results BLOOM IVF F – LILAVATI 2010
2010: Total ET % Pos
70
Average: 50.8%
60 57.5 56 54 4.5
50.5
49.1
49.3
51.1
50
50
40
30
20
10
0 1. Jan 2. Feb 3. Mar 4. Apr 5. May 6. Ju un 7. July 8. Aug 9. Sept 10. Oct 11. Nov 12. Dec
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
45.3
47.3
48.2
IMSI – Late est & Best
A new method of high magnification (×7200) motile
sperm organellar morphol logy examination (MSOME) published by Bartoov et al l. in 2002 They found that the couples who underwent IMSI had gnancy rate (66%) than those a significantly higher preg who underwent conventional ICSI (33%). However, this was based on o a small sample size.* IMSI, as the name suggest ts, is the technique of selecting the most normal l looking sperm by magnifying it to about 720 00 times. * Bartoov B B, et al al.. Fertil Steril ,2003 2003
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Figure : Sperms magnified 72 200 times to identify vacoules
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Since then numerous studies s have been
performed with encouraging results in favor of the IMSI procedure.
Does the presence of nuclear vacu uoles in human sperm selected for ICSI affect pregnancy outcome
Ber rkovitz A, et al Human Reproduction 21, 2006.
How to improve IVF–ICSI outcome e by sperm selection.
Berkovitz A, et al Reproductive BioMedicine Online 2006.
High-magnification ICSI overcomes paternal effect resistant to conventional ICSI.
Hazout H t A, et t al l Reproductive R d ti BioMedicine Bi M di i Online O li 2006
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Rita de Cassia S. Figu ueira, Fertility and
IM MSI
S ili article Sterility i l to be b published bli h d Spermatozoa free of nuclear morphological malformations were found f to be significantly associated with the lo ower incidence of aneuploidy p y in derived d embryos, y , resulting g in lower rates of cycle cancellation. c
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
IMSI v/s v ICSI
Intracytoplasmic sperm injection outcome versus
intracytoplasmic morpholo ogically selected sperm injection outcome: a meta a analysis a-analysis. This is the first meta-ana alysis of published data to evaluate the potential ben nefits of IMSI. IMSI The pooled data of IMSI cy ycles demonstrate a statistically significant imp provement in implantation and pregnancy rates and a statistically significant reduction in miscarriage g rates. r However, more randomize ed controlled trials are needed to confirm these results. r
Souza Se etti A, Reprod Biomed Online. 2010 Oct
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
ancy and implantation rates arising from ICSI Table 1: Comparison of fertilization, pregna & IMSI groups. Continuous variables are presented as means ± SD; aP < 0.05; bP < 0.05.
Group 1, ICSI (n=100) 32.91 ± 3.30 1.65 ± 1.57 Group p 2, IMSI I (n=92) 32.65 ± 3.23 Unpaired t-test applied t-value p-value Difference is: -0.530 0.17 -1.759 -1.763 9.078 0.103 4.457ˆ 6.960ˆ 0.5963 0.8652 0.0802 0.0794 <0.0001 0.9184 0.0347 0.0083 Not Significant Not Significant Not Significant Not Significant Not Significant Not Significant Significant Significant
Mean age (years)
Number of previous ICSI 1.69 ± 1.69 failures Number of oocytes recovered 10.39 ± 9.58 ± 3.34 3.04 Number of injected oocytes 8.92 ± 0.26 8.85 ± 0.29 Number of 2 PN zygotes Number of transferred embryos/patient Clinical pregnancy rate (%) Implantation rate (%) 6.66 ± 0.42 7.23 ± 0.45 2.81 ± 0.67 2.82 ± 0.68 36/100 (36)a 56/281(19. 93)b; 2 twins 48/92 2 (52.17)a 78/25 59 (30 12 (30.12 2)b; 4 twins
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Table 2. Comparison of pregnancy arising from f intracytoplasmic sperm injection (ICSI)
& intracytoplasmic morphologically selecte ed sperm injection (IMSI) sub-groups with a different number of p previous IVF failures failures.
Sub-group
Subgroup A (0 ICSI failures)
Rate
Pregnancy No Pregnancy Total % Pregnancy Rate Pregnancy No Pregnancy Total % Pregnancy Rate Pregnancy P No Pregnancy Total % Pregnancy P R Rate t
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
PIC CSI
‘‘Physiologic ICSI’’: Hy yaluronic acid (HA)
favors selection of spe ermatozoa without DNA fragmentation f an nd with normal nucleus, resulting in improvement of embryo quality.
– Lodovico Parmegiani,, Fertility and Sterility January, 2010
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Conclusion
Treatable Infectious like filariasis, epididymitis, accessory gland infection Semi-treatabl le Empirical Heat exposure Smoking Alcohol Stress CC /Gn Zn l-Carnitine Antioxidants CoQ10 Lycopene ART IUI IUI-D IUI D ICSI IMSI PICSI
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 2 , Lilavati Hospital Mumbai
Dr Nandita Palshetkar , First Vice-President FOGSI 2011 , Lilavati Hospital Mumbai