Atosiban is a oxytocin receptor antagonist that can be used during embryo transfer in IVF cycles to reduce uterine contractions and improve implantation rates. Several studies have shown Atosiban: 1) Significantly decreases uterine contractions and improves endometrial characteristics like thickness and blood flow compared to controls. 2) Increases implantation rates from 12.6% to 20.4% and clinical pregnancy rates from 28.9% to 46.7% compared to placebo in IVF patients. 3) Improves implantation rates from 0% to 43.7% and pregnancy rates in patients with repeated implantation failure undergoing frozen embryo transfers. 4) May be administered as a 6.75mg IV

1. Role of
Atosiban
In ART
Dr Jyoti Agarwal

2. Exponential increase in IVF
Procedures in India

3. India performs approx 1 Lac IVF cycles annually &
55% of these IVF cycles are performed in the top eight metro cities

4. The ART Boom
The IVF cycles are expected to grow at approx 20% p.a
Current 1 Lac cycles will increase to 2.6 Lac cycles by 2020

5. Success of IVF
80% women undergoing IVF
reach Embryo Transfer
stage………………….
but Pregnancy Rates are Low
Implantation is still considered as
“ Black Box ” of IVF

6. Embryo Transfer
Final & most
crucial step of
IVF cycle
Success of IVF

7. Embryo Transfer should be
Absolutely Gentle and Least Traumatic
• Procedure itself increases release of local oxytocin &
prostaglandins
• Any additional manipulation of the vagina or cervix, such
as the use of ellis tenaculum provides an additional
stimulus for oxytocin & prostaglandin release which
further increases uterine contractions.
Dorn C. Eur J Obstet Gynecol Reprod Biol. 1999 Nov;87(1):77-80.

8. The Embryo Transfer Procedure
• Uterine contractile activity in IVF cycles is
increased by approx 6-fold before embryo
transfer as compared to ovulation in the
natural cycle
• About 30% of patients undergoing embryo
transfer have pronounced uterine
contractions
Cavagna M, Mantese JC. 2003 Oct;24 Suppl B:S39-47.

9. The embryo Transfer Procedure
• < 50% of transferred embryos remained in the
uterus 1 hr after transfer
• About 15% of embryos could be found in the
vagina after embryo transfer
• Uterine contractile activity at the time of embryo
transfer could expel embryos from the uterus
Ayoubi JM. Fertil Steril. 2003 May;79(5):1101-5

10. • IVF cycles induce an abundant increase in oestradiol
concentrations which are about 10–20 nmol/l at the end
of ovarian stimulation as compared to less then 2 nmol/l
in the natural cycle
• Supra-physiological concentrations of oestradiol induces
local endometrial production of oxytocin, formation of
oxytocin receptors, & formation & release of PGF2α
which is similar to the prelabor status
Novel target in fertility treatment
Pierzynski P. Reprod Biomed Online. 2011 Jan;22(1):9-16.

11. • During the very last days of ovarian stimulation
in IVF the endocrine situation ,results in
oxytocin receptor status which resemble those
seen before the onset of labor thus resulting in
increased excitability of the uterus
Novel target in fertility treatment
Akerlund M. Prog Brain Res. 2002;139:359-65.

12. Measures at the time of embryo transfer
to reduce uterine contractions
• Use of a soft catheter
• Avoid touching the uterine
fundus
• Use of ultrasound to guide
embryo transfer.
• Use of DRUGS to reduce
uterine contractions.

13. Atosiban: Application in Embyo-Transfer
Atosiban improves uterine receptivity by
1. Reducing uterine contractions
2. Reduction in intrauterine PGF2α production &
3. Improving uterine blood supply: Atosiban
preferentially relaxes uterine arteries which in turn
increases uterine perfusion
These potential benefit are useful for
implantation during embryo transfer
Pierzynski P. Reprod Biomed Online. 2011 Jan;22(1):9-16.

14. Effect of atosiban on uterine contraction
waves during embryo transfer
A) Four-minute recording of uterine contractions before the atosiban infusion
B) Recording of uterine contractions after 1 h of infusion
Dotted circles mark uterine contractions.

15. Effect of Atosiban : Human Endometrium
In IVF program using USG
Atosiban Group - 13 pts
 Echogenic endometrium in 1 case
(7.7%), triple line endometrium in 12
cases (92.3%),
 Endometrial thickness >7 mm in all
cases,
 Endometrial volume >2.31 cm3 in 11
cases (84.6%),
 Abnormal sub-endometrial halo in 3
cases (23.1%),
 Endometrial blood flow in 11 cases
(84.6%) &
 Complex vessel’s architecture in 6
cases (46.2%).
The Control Group - 13 pts
 Echogenic endometrium in all cases,
 Endometrial thickness >7 mm in all
cases (84.6%),
 Endometrial volume >2.31 cm3 in 5
cases (38.5%),
 Abnormal sub-endometrial halo in 3
cases (23.1%),
 Endometrial blood flow in 6 cases
(46.2%) and
 Complex vessel’s architecture in 2
cases (15.4%).
Women who have taken Atosiban presented an
endometrium with characteristics more predictive of implantation
Kalmantis K. Arch Gynecol Obstet. 2012 Jan;285(1):265-70.
26 pts

16. Published
Clinical Studies

17. Atosiban Treatment before embryo transfer
increases implantation rates in IVF
• RCT (2010) enrolled
• 180 women undergoing IVF /ICSI who had top-quality embryos
were randomly allocated into treatment and control groups.
• All the patients had infertility due to tubal factor, hormonal-
anovulatory disorders, male factor or unexplained reasons.
• The treatment group received IV administration of
atosiban before embryo transfer with a total dose of
37.5 mg.
• In the control group, the same number of cycles was
performed with placebo medication.
Moraloglu O. Reprod Biomed Online. 2010 Sep;21(3):338-43.

18. Atosiban Treatment before embryo transfer
increases implantation rates
Uterine contractions
decreased from 11
contractions per 4 min
to 7 contractions per
4 min as well as
decrease in their
amplitude

19. Atosiban
group
Control
group
P-value
Implantation rate % 20.4 (57/279) 12.6
(34/270)
0.01
Clinical pregnancy rate % 46.7 (42/90) 28.9 (26/90) 0.01
Miscarriage rate (%) 16.7 24.4 0.01
Outcomes of IVF–Embryo transfers
in the control & Atosiban groups
P < 0.05 is considered to be statistically significant
These results suggest that Atosiban treatment
before embryo transfer is effective in priming of
the uterus for implantation

20. Atosiban improves implantation &
Pregnancy rates in patients with
repeated implantation failure

21. Atosiban improves implantation & pregnancy
rates in patients with RIF
• Study enrolled 71 women with repeated implantation
failure using cryopreserved embryos
• The implantation rate per transfer was 13.9% &
clinical pregnancy rate per cycle were 43.7%.
Pregnancy rate went from 0 % to 43.7%
Lan VT. Reprod Biomed Online. 2012 Sep;25(3):254-60.

22. Dose of Atosiban in IVF
• Atosiban is administered as an i.v. bolus of 6.75
mg , 30 min prior to embryo transfer
• Followed by i.v. infusion at a rate of 18 mg/ hr
for 1 hr and then reduce to
• 6 mg/ hr for next 2 hr.
Total dose administered 36.75 mg in 3 hrs
Lan VT. Reprod Biomed Online. 2012 Sep;25(3):254-60.

23. Method of administration
Available in 2 different packs
Stage Regimen Atosiban
dose in
ml
Atosiban
dose in
mg
With 100 ml
infusion bottle
Time
1 30 minutes prior to
embryo transfer
give 0.9 ml iv bolus
over 1 min
0.9 ml 6.75 mg Bolus IV
injection
1
minute
2 followed by
continuous
intravenous
infusion for 1 hour
4.1 ml
In 100 cc
NS
18 mg /
hr
20 drops/min 1 hour
3 Subsequent
intravenous
infusion for 2 hours
6 mg/hr 6 drops/min 2 hours
Moraloglu O. Reprod Biomed Online. 2010 Sep;21(3):338-43.
4.1 ml

24. Lower dose of Atosiban may also improve pregnancy
outcomes of patients with RIF
• Total 150 infertile couples with RIF undergoing IVF-ET were
divided into three groups.
– (Group 1): 80 Patients who did not receive atosiban were used
as controls.
– (Group 2): 40 patients received a single bolus dose (6.75mg,
0.9mL/vial) of atosiban before ET &
– (Group 3): 30 patients received a bolus dose of 6.75mg
atosiban followed by infusion at 18mg/hr for 3 hours
immediately after ET Chou PY. Taiwan J Obstet Gynecol. 2011 Jun;50(2):136-40.

25. Parameters Group 1
(n=80)
(control
group)
Group 2
(n = 40)
(single bolus
dose of
Tractocile)
Group 3
(n =30)
(infusion dose of
Tractocile)
p
Number of embryos
transferred (mean)
2.23 ± 1.10 2.35 ± 0.99 2.37 ± 1.14 0.85
Implantation rate 11.8 (21/178) 30.21 (29/96) 15.9 (11/69) 0.0006*
Clinical pregnancy
rate
12.5 (10/80) 37.5 (15/40) 20 (6/30) 0.0057*
Miscarriage rate 20 (2/10) 6.67 (1/15) 16.6 (1/6) 0.62
Live birth rate 10 (8/80) 35 (14/40) 16.67 (5/30) 0.0031*
Multiple pregnancy
rate
10 (1/10) 40 (6/15) 16.67 (1/6) 0.22
Study revealed that …..
Chou PY. Taiwan J Obstet Gynecol. 2011 Jun;50(2):136-40.

26. Pharmacovigilance
No important safety issues since
launch of Atosiban in 2000
Ronald F Lamont. Expert Rev. Obstet. Gynecol. 3(2), 163–174 (2008).

27. Embryonic safety of Atosiban
Rabbit Embryo Bioassay
Human sperm motility bioassay
• Atosiban did not: affect the survival of one-cell rabbit embryos,
• Atosiban did not affect human sperm motility in
concentrations, 10 times the human mean plasma concn.
• Both studies failed to detect an embryotoxic effect of
atosiban in concentrations up to 50-times the
therapeutic blood concn .
Pierzynski P. Fertil Steril. 2007 May;87(5):1147-52.

28. Packaging & Storage
Store at 20c to 80c. Do not Freeze
Store in the original packet in order to protect from light

29. Published in
Journal of Human
Reproduction Sciences
By Dr. Vineet Mishra
Prof & Head Dept of Obst. Gyn.
IKDRC, Ahmedabad, Gujarat
Objective: To Evaluate the efficacy of Atosiban
in embryo transfer in terms of
implantation rate, clinical pregnancy rate and
ongoing pregnancy rate and to assess its
safety
N = 320 women undergoing In-vitro
Fertilisation Embryo Transfer

31. Atosiban in IVF cycles at
Atosiban Group
(23 Patients )
No Atosiban Given
(23 Patients )
Pregnancy
28 - 30 %
Pregnancy
30 - 32%
Two Small a Study for any comments
Consecutive 46 patients enrolled for self IVF cycles
Bolus
dose only

32. Delhi Data
• Dr .Seema Sehgal • Dr. Sudha Prasad

33. To conclude
Atosiban improves
uterine receptivity during
ET and thus may increase
success rates in
• Fresh cycles,
• Frozen cycles and also in
• Pts with RIF

34. Thank you
all