Invited debate by Dr Sujoy Dasgupta in East Zone Yuva FOGSI, held through Webinar in June, 2021

1. Dr Sujoy Dasgupta
MBBS (Gold Medalist, Hons)
MS (OBGY- Gold Medalist)
DNB (New Delhi)
MRCOG (London)
Advanced ART Course for Clinicians (NUHS, Singapore)
Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata
Visiting Consultant, RSV Hospital, Kolkata
Bhagirathi Neotia Women and Child Care centre
Woodlands Multispeciality Hospital, Kolkata
Managing Committee Member, Bengal Obstetric & Gynaecological Society (BOGS)
Secretary, Subfertility and Reproductive Endocrinology Committee, BOGS
Executive Committee Member, Indian Fertility Society (IFS)- West Bengal Chapter
Executive Committee Member, Indian Society for Assisted Reproduction (ISAR)- Bengal
Member, Endocrinology Committee, Federation of Obstetric and Gynaecological Societies of
India (FOGSI)
Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
Preferred Route of Progesterone for LPS-
VAGINAL

2. Why Vaginal route is preferred?
• Delivers where needed (“First uterine pass
effect”)
– Direct diffusion : within 6 hrs of administration
– Counter-current exchange- concentrations in
uterus : periphery - 14:1, IM –1:1.
• The bioavailability of vaginal progesterone is
about 40-fold greater than that of oral
progesterone

4. Fanchin et al., 1997
Transvaginal administration of progesterone
induced normal secretory transformation of
the endometrium
despite low plasma levels,
suggesting a direct transit into the uterus or "first
uterine pass effect."

5. • After vaginal progesterone application, discrepancies have
been detected between serum progesterone values and
histological endometrial features.
• Vaginally administered progesterone results in adequate
secretory endometrial transformation, despite serum
progesterone values lower than those observed after i.m.
administration, even if they are lower than those observed
during the luteal phase of the natural cycle.
• This discrepancy is indicative of the first uterine pass effect
and therefore of a better bioavailability of progesterone in
the uterus, with minimal systematic undesirable effects.

6. Oral Progesterone
• Bioavailability <10%
• Poorly absorbed from GIT
• First pass metabolism by
the liver
• Allopregnanolone and
pregnanolone circulate at
higher concentrations-
CNS depression in some
women
Vaginal P4-
1. No supraphysiological
levels of neurosteroid
metabolites
2. No spikes or marked
fluctuations in
neurosteroid levels

7. • There was a higher rate of maternal adverse
effects with oral progesterone that included
dizziness (relative risk, 2.95; 95% confidence
interval, 1.47e5.90) somnolence (relative risk,
2.06; 95% confidence interval, 1.29e3.30), and
vaginal dryness (relative risk, 2.37; 95%
confidence interval, 1.10- 5.11
Boelig RC, Della Corte L, Ashoush S, McKenna D, Saccone G, Rajaram S, Berghella V. Oral
progesterone for the prevention of recurrent preterm birth: systematic review and metaanalysis.
Am J Obstet Gynecol MFM. 2019 Mar;1(1):50-62.

8. Oral Micronized P4
• Totally absorbed from GIT
• Highly metabolized by the liver

9. Increasing dose of oral P4
• E2- liver metabolism is
overcome by increasing
daily dose of oral E2
• P4- Doses up to 1 g/24
hours failed to reliably
induce pre-decidual
changes in the
endometrium,

10. Oral Dydrogesterone
Oral Progesterone
Vs
Vaginal Progesterone
Oral Dydrogesterone
Vs
Vaginal NMP

12. LOTUS Trials
• LOTUS I and LOTUS II- Not powered to
assess live birth
• LOTUS II- Not blinded
• On Fresh ET only

14. • Different routes of progesterone administration
- comparable pregnancy rates and pregnancy
loss rates to vaginal and intramuscular
progesterone.
• In the frozen-thawed embryo transfer,
dydrogesterone is not effective as
monotherapy treatment

16. A = random sequence
generation
B = allocation concealment
C = blinding of participants
and personnel
D = blinding of outcome
data
E = incomplete data
F = selective reporting
G = other bias.
Quality of evidences

17. • Substantial heterogeneity (>50%) was found for all
side effects reported by the three studies
• Therefore the results were not pooled together.
• Two studies did not describe differences in reported
side effects
• Onw study showed that dydrogesterone was
associated with more cases of vaginal bleeding (RR
2.38; 95% CI 1.18 to 4.78), nausea (RR 21.00; 95%
CI 1.27 to 346.66), and abdominal pain (RR 13.00;
95% CI 0.76 to 223.33) when compared to vaginal
progesterone capsules.

18. Vaginal Progesterones
Vaginal Gel (8%) in Polycarbophil base
• Special applicator – easy to use with no wastage
of drug
• Excellent vaginal moisturizing property
Beckham et al, Clinical practice in sexuality, Vol.8, No.8/9. page 3-8

21. Patient Satisfaction
• Barbosa et al., 2018
• Two studies reported patient dissatisfaction with treatment
(Chakravarty et al., 2005; Saharkhiz et al., 2016)
• Since the two studies were significantly heterogeneous (I2 = 91%),
their results were not pooled together.
• Chakravarty et al. (2005) described a great benefit of
dydrogesterone in reducing patient dissatisfaction: 3% in women
using dydrogesterone vs. 26% in women using vaginal progesterone
capsules; RR 0.10, 95% CI 0.02 to 0.39; 430 women.
• Saharkhiz et al. (2016) reported no difference in dissatisfaction
between groups: 8% in women using dydrogesterone vs. 7% in
women using vaginal progesterone capsules; RR 1.19, 95% CI 0.46
to 3.04; 210 women.

22. Uterine contractility

23. Areeruk, W., & Phupong, V. (2016). A randomized, double
blinded, placebo controlled trial of oral dydrogesterone
supplementation in the management of preterm labor. Scientific
reports, 6, 20638. https://doi.org/10.1038/srep20638
• In the present study, recurrent uterine
contraction after completing a 48-hour course
of tocolysis was lesser in the dydrogesterone
group than in the placebo group (87.5% vs
91.7%), but there was no statistical
significance.
• Thus, dydrogesterone does NOT have a role
as tocolytic agent.

24. Cost???

25. Vaginal formulations?

26. Vaginal scan

27. Topical or oral?

28. How you can counsel

29. Just simply you cannot