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Unlocking I.V.F Services
Redefining the New Normal
Dr. Sharda Jain
SECRETORY GENERAL D.G.F
DIRECTOR LIFECARE CENTRE /LIFECARE IVF
Transfer of an
embryo into the
uterus
Culture in
laboratory
Fertilization of
eggs with sperms
to create embryos
Egg collection
under sedation
Ovarian stimulation
using gonadotropin
hormones
Sullivan-Pyke CS, et al. Semin Perinatol. 2017;41(6):345–353.
1 in 8 couples experience
difficulty in conceiving.
In Vitro Fertilization: Unlocking the Key to Infertility
IVF
Increasing Demand for IVF –
A New Paradigm of Parenthood
Eskew AM, Jungheim ES. Mo Med. 2017;114(3):156–159.
The increasing demand for fertility treatment drives research and
development of technologies to optimize IVF regimens and success
Maternal Age
Genetic
relatedness
Lifestyle
Gestational
carriers
Genetic
abnormalities
Which are most popular
Investigations in Evaluations prior to IVF?
Investigations and Evaluations Prior to IVF:
Blood Tests
Mutlu MF, et al. J Turk Ger Gynecol Assoc. 2012;13(3):196–203.
IVF: In vitro fertilization; FSH: follicle-stimulating hormone; GnRH: Gonadotrophin releasing hormone.
Basal serum
FSH levels
Basal
serum
estradiol
level
Basal serum
inhibin-B
level
Anti-
Mullerian
hormone
GnRH
stimulation
test
Exogenous FSH
ovarian reserve
test
1
2
3
4
5
6
7
Clomiphene citrate
challenge test
Semen
analysis2
+ DFI
Evaluation of UTERUS
2
• Hysterosalpingogram
• Saline infusion
sonohysterography
• Hysteroscopy
• Trial or mock transfer
Ultrasonography1
• Ovarian volume
• Total ANTRAL
FOLLLICLE Counts
• Ovarian stromal blood
flow
Other Investigations and Evaluations Prior to IVF
1. Mutlu MF, et al. J Turk Ger Gynecol Assoc. 2012;13(3):196–203. 2. Society for Assisted Reproductive Technology. Available at: https://www.sart.org/patients/sart-patient-
evaluation/#:~:text=The%20uterus%20is%20usually%20evaluated,and%20direction%20of%20the%20uterus. Accessed on: 19 August 2020.
Sonographic assessment of
OVARIAN RESERVE is advantageous
in selecting poor responders and choosing
appropriate stimulation protocols at the
beginning of the cycle
Prior to IVF, a trial or
“MOCK” TRANSFER may be done to
determine the length and direction of the
uterus
OR
RECOMMENDATIONS on good practices
during the current pandemic?
Good Practices for Resumption of Reproductive Care
SIX PILLARS of good medical practice proposed for the restart
of activity in the ART clinic and laboratory are:
Discussion,
agreement and
consent to the start
of treatment
Staff and patient
triage
Access to
advice and
treatment
Adaptation of ART
services
Treatment cycle
planning
Code of
Conduct for
staff and
patients
ART: Assisted reproductive technology.
ESHRE guidance on recommencing ART treatments. Available at: https://www.eshre.eu/-/media/sitecore-
files/Guidelines/COVID19/ESHRE-Guidance-on-Recommencing-ART-treatments_update-
04052020.pdf?la=en&hash=A584F8A306C570BE7648C167CB190F994E21F05A. Accessed on: 16 August 2020.
Discussion, Agreement before the Start Treatment
ART: Assisted reproductive technology.
ESHRE 16 August 2020.
Patients must sign and
adhere to the Code of
Conduct and agree to
discontinue treatment if
necessary.
Inform patients about the
Risk and Prevention
of viral infection.
High-risk patients should
not start ART treatment
until permitted by relevant
healthcare professionals.
Offer the choice of
proceeding or postponing
ART treatment and
document patient
preference.
Staff Triage and Management
STAFF
Triage
questionnaire
2 weeks
prior to the start
of clinic activities
Start work
Occupational health
advice & self
quarantine
Test for antibodies
(IgM, IgG)
Asymptomatic
Triage negative
Triage potentially
positive
Mild/nonspecific symptoms
?
+
Specific symptoms and/or a
previous viral test
Triage
positive
+
–
Ig: Immunoglobulin; SARS-CoV: Severe acute respiratory syndrome-associated coronavirus.
ESHRE 16 August 2020.
–
Patient Triage and Management
Patients
Triage
questionnair
e
2 weeks
prior to the
start of
treatment
Include
Exclude
Be open minded
Patients/partners asymptomatic
Triage negative
Triage potentially
positive
Mild/nonspecific
symptoms
?
+
Specific symptoms and/or
a previous viral test
Triage positive
+
–
–
Test for
antibodies
(IgM, IgG)
ESHRE 16 August 2020.
Adaptation of ART Services is just like any
surgery Settings
Specific sanitation
procedures
ART centers to
guarantee continuity of
treatment provision
Limited access,
social distancing,
Follow-up after 3 weeks of
oocyte retrieval and/or
embryo transfer, to
identify potential virus
positive patients
ESHRE 16 August 2020.
Treatment Cycle Planning
Ovarian stimulation monitoring
• Minimal exposure for both staff
and patients
• Minimal number of visits and
optimized number of blood tests
• Vaginal probe and tissue hygiene
Oocyte retrieval
• Follow standard procedures unless
changes occur between ovulation
trigger and oocyte retrieval
• If patients tests positive for viral
infection , postpone treatment, refer,
and isolate
• Exceptions for oncology patient or
patient at high risk of OHSS
Embryo transfer
• Limit the number of staff members in the
transfer room
• Perform transfer only in cases of low
risk/asymptomatic patients and
partners
• Apply freeze-all policy for all patients
and/or partners who became symptomatic
after the oocyte retrieval
Cryopreservation
• High security straws and/or vapor
phase storage tanks should be
used for cryopreservation of
samples from virus positive
patients
ESHRE 16 August 2020.
FRESH OR FROZEN EMBRYO TRANSFER:
The choice on resumption of practice?
Resumption of Infertility Treatment Should Be
Under Strict Infection Control Measures
COVID-19: Pause Infertility and Reproduction Treatments? Available at: https://www.medicinenet.com/covid-
19_infertility_and_reproduction_treatments-news.htm. Accessed on: 17 August 2020.
Diagnostic
infertility
testing
FET and IUI
Less
invasive
procedures
Ovarian stimulation,
oocyte retrieval and
embryo transfer
Invasive lengthy
procedures
The resumption
of practice will
be done in a
stepwise
fashion.
Strict infection control measures are
mandatory during the reopening of
practice.
FET: Frozen embryo transfer; IUI: Intrauterine insemination.
FROZEN EMBRYO TRANSFER Will Be the Choice of
Treatment After Resumption of Practice
Deferred FET is the best choice
for women already on their
preparatory phase of ART
treatment, which can be as long as
several months.
Ideal solution for women
who cannot postpone their
ovarian stimulation without
incurring a risk of reducing
their chance of success.
No compromise
regarding overall chance
of pregnancy
Frozen embryo transfer will
be the treatment of choice
after resumption of fertility
practice.
Tesarik J. Reprod Biomed Online. 2020;40(6):760–762.
Rationale Behind Success With
Frozen Embryo Transfer
Embryo transfers are disengaged from ovarian
stimulation in the ovarian stimulation cycle.1
Primary objective of FET cycles is adequate preparation of the
endometrium to receive the thawed embryos.1
Supraphysiological
hormonal levels
achieved at the end
of COS2
Negatively affect
the endometrial
receptivity in fresh
ET2
Adversely affect
implantation rates in
fresh ET2
Fresh ET
Adverse effects
induced by COS
disappear in the
following cycle2
FET can be
successfully
performed2
FET
FET
FET Cycles Are Associated With a Decreased
Risk of Low Birth Weight and Preterm Delivery
Low birth weight Preterm delivery
Small for gestational
age
Placenta previa,
placental abruption
Compared to fresh ET, pregnancies resulting from FET are
associated with lower risk of:1,2
Lets Talk-- in which patient profile is
FROZEN EMBRYO TRANSFER
most advantageous?
Who Would Benefit From the Freeze-All Policy?
Patients with
an altered
endocrine and
CV profile
Patients at
risk of
OHSS
Patients with
inadequate
uterine cavity
for Embryo
transfer
Patients
who are
Hyper-
responders
Patients
undergoing
PGT-A at the
Blastocyst
stage
Some probable indications for freeze-all embryo cycles are:1,2
OHSS E+CV ET HR PGT-A
FET Is Beneficial in High Responders
Acharya KS, et al. Fertil Steril. 2018;110(5):880–887.
FET cycles have
higher pregnancy
rates than fresh
transfers in high
responders
(with 15 or more
oocytes retrieved).
High
responders
Intermediat
e
responders
Low
responders
FET cycles vs. fresh ET cycles
 CPR: 61.5 % vs. 57.4%
 LBR: 52.0 % vs. 48.9%
 CPR: 44.2% vs. 49.6%
 LBR: 35.3% vs. 41.2 %
 CPR: 15.9% vs. 33.2%
 LBR: 11.5% vs. 25.9%
Higher
after fresh
cycle
Higher
after fresh
cycle
Higher
after FET
cycle
FET for All Normal Responders?
FETs are associated with an increased
implantation rate, CPR, and ongoing pregnancy
rate.
Roque M et al. 2015 study1
Differences in implantation rate and ongoing
pregnancy rate were being driven by the higher
responders with 10–15 oocytes retrieved.
Roque M et al. 2017 study2
Implantation rates Ongoing pregnancy
rates
Fresh cycle FET Fresh cycle FET
Group 1
(4–9 retrieved oocytes)
17.9% 20.5% 31% 33%
Group 2
(10–15 oocytes)
22.1% 30.1% 34% 47%
Lets talk How can the COMPOUNDED
STRESS during the current pandemic
affecting an ART Patients ?
Risks of Compounded Stress During IVF
Changes in
sleeping/
eating
patterns
Worsening
of chronic
and mental
health
problems
Stress
and
anxiety
Disturbs the necessary balance of
hormonal conditions required
to become pregnant
Automatic hormonal release elevates
heart rate, increases blood pressure,
and boosts energy
Causes physiological and psychological
damage
Tips to Handle Compounded Stress
05
04
03
02
01
DIGITAL DETOX
Use relaxation/mindfulness
MEDITATION
Collect information from reliable
sources like WHO, CDC, ASRM
Interact with support
groups
Self-help books and positive
SELF-TALK are powerful
Recommendations for reducing the
RISK OF VIRAL TRANSMISSION
during fertility treatment
Recommendations for Reducing the Risk
of Viral Transmission
Couples proceeding to ART need repeated viral screening to
minimize risk of viral transmission to partners and offspring.
Samples from viral
carriers be processed
in a separate
laboratory or
designated space.
Fertility centre should be
equipped to treat couples
POSITIVE for viral
diseases.
Pre-conceptional
counseling on the risks
of sexual and vertical
transmission of
infections should be
provided.
The following measures have been proposed to further reduce the risks of
CROSS CONTAMINATION of samples in liquid nitrogen storage:
Practice Committee of American Society for Reproductive Medicine. Recommendations for
reducing the risk of viral transmission during fertility treatment with the use of autologous
gametes: A committee opinion. Fertil Steril. 2013;99(2):340–346.
Recommendations for Reducing the Risk of Cross
Contamination of Samples in IVF Lab
Specimen containers
should be able to withstand
freezing temperatures and
thawing cycles
Use ‘‘double bagging’’ or
sealing techniques to
prevent direct contact of
cryocontainers with liquid
nitrogen
Storage of samples in
liquid nitrogen vapor
‘‘Sperm-washing’’ to
decrease the
viral load before freezing
semen samples
Joint ISAR-IFS-ACE recommendations
22 Dec 2020
on Rresuming ART Services
Willingness to
start services
in a phased
manner
Sufficient
staff,
facilities,
and
consumable
s
Clear
policies on
number of
cycles/
patients the
clinic can
handle
Fair and
scientific
approach on
making their
policies on
education
and training
of staff
Willing to triage
patients and
undertake only
patients tested
or screened
negative as per
the existing
regional policy
Close liaison
with another
clinic
Written
code of
conduct for
patients
and staff
Arogya Setu
app
downloaded
on patient’s
cell phones
before start of
the treatment
a must
Patient Selection and Prioritization for
Fertility Services
Patient selection
Patient prioritization to
be based on
• Avoid high-risk patients
• Avoid third-party reproduction, (donor with
fresh oocytes and surrogate cycles)
• Start ART cycles for fertility preservation in
cancer survivors at the earliest
• Prefer low-risk cases that would require
minimum clinic visits
• Impact of delay on patient prognosis
• Impact of treatment delay on the mental
and emotional well-being of patients
Joint ISAR-IFS-ACE recommendations
22 Dec 2020
ESHRE GUIDANCE
(22 December 2020).
on Resuming Fertility Treatments (1/2)
More Testing Increased counseling
and information to
patients planning a
pregnancy or already
pregnant
ESHRE Guidance on Resuming Fertility
Treatments (2/2)
Decrease the number
of patients treated
Limit access to
treated patient only
(no partners)
Increase patient and
staff triage and
testing
Limit staff exposure
and allow more time
between patient
appointments
Enhance sanitation
measures
Use PPE intensively
Increase the use of
telemedicine
Avoid embryo transfer
and advise a freeze-all
strategy to all patients,
particularly in high
viral–incidence areas
Reaffirm the Code of
Conduct
EMERGENCY MEASURES
for Clinics During the Pandemic
ESHRE 22 December 2020.
Clinics may need to temporarily
reduce or even suspend their
activity as a result of staff
shortages.
All ART centers should have
agreements with other centers to
guarantee continuity of treatment.
Recommendations for Centers and Clinicians
Centers
Clinicians
• Monitor epidemiological data.
• Monitor internal and external risk factors, which
may have an impact on ART services, including
but not limited to staff number and availability
of supplies.
• Consider mitigation measures to reduce these
risks.
• Inform their patients about the risk of infection
before and during pregnancy.
• Routine testing of asymptomatic staff and
patients (based on service-specific protocols)
should be considered
ASRM Task Force Guidelines on Resuming
Practices 22 December 2020.
The impact of delay on patient prognosis
due to medical factors, such as age, ovarian
reserve, or endometriosis
The number of patient visits required
The impact of treatment delay on the
mental and emotional well-being of
patients
The impact of delay on patient ability to
pursue or access treatment due to insurance
coverage or employment status.
Vertical transmission of the virus
From mother to fetus
During the current pandemic?
Chances of Vertical Transmission of Virus is Rare
Neonates delivered by positive mothers
have tested negative for the virus.
Evidence for intrauterine infection caused by vertical
transmission in late pregnancy is lacking.
The consequences of infection among
women during early pregnancy is unknown.
Although evidence of
vertical transmission
of is still unclear, it
may be POSSIBLE.
Mimouni F, et al. J Perinatol. 2020;40(5):820–6.
Vertical Transmission of Virus is Rare
But Possible
Mimouni F, et al. J Perinatol. 2020;40(5):820–6.
What are the adapted IVF protocols in the
Current Scenario?
INDIVIDUALIZATION Of Treatment In IVF
La Marca A, et al. Hum Reprod Update. 2014 ;20(1):124–140.
Individualization
of
treatment in IVF
Best treatment
tailored to
patient’s unique
characteristics
Maximizing
the chances of
pregnancy
Eliminating the
avoidable risks
resulting from
ovarian
stimulation
PERSONALIZATION OF TREATMENT IN IVF SHOULD BE
BASED ON THE PREDICTION OF OVARIAN RESPONSE
Normal
responders
POOR
responders
HYPER
responders
Preferred Timing of Initiating Ovarian Stimulation
Early follicular
phase
stimulation
Luteal phase and
‘random start’
stimulation
Double/dual stimulation
(DuoStim)
Ovarian stimulation is
started any time
throughout the cycle.
Two stimulations and
oocyte retrievals are
performed on the same
cycle.
Ovarian stimulation may be initiated anytime throughout the menstrual cycle
Evidence indicates that luteal phase or ‘random
start’ stimulation compared to follicular phase
stimulation results in:
• Significantly higher number of mature
oocytes
• Top-quality embryos
• Higher live birth and ongoing
pregnancy rates
39.2%
44.4%
0
5
10
15
20
25
30
35
40
45
50
FPS LPS
Timing of ovarian stimulation
Ongoing
pregnancy
and
live
birth
rates
p=0.012
Pregnancy outcomes
Freeze-all
Mizrachi Y, et al. Hum Reprod Update. 2020;26(1):119–36.
FPS: Follicular phase stimulation; LPS: Luteal phase stimulation.
CC: Clomiphene citrate; Gn: Gonadotropin mixtures; GnRHa: Gonadotropin releasing hormone agonist; GnRHant: Gonadotropin releasing
hormone antagonist; hCG: Human chorionic gonadotropin; hMG: Human menopausal gonadotropin; IU: International units; IVF: In vitro
fertilization.
Shrestha D, et al. Ann Transl Med. 2015;3(10):137.
GnRH agonist protocol
(Long protocol)
GnRH antagonist protocol
(Short protocol)
Minimal stimulation
protocol
Day 21 (previous cycle): 0.1 mg GnRHa
Day 2: 150–225 IU Gn + 0.1 mg GnRHa
Day 15/16: hCG injection
Day 2/3: 150–225 IU Gn
Day 6: 0.25 mg GnRHant + 150–225 IU Gn
Day 15/16: hCG injection
Day 2/3: 150–225 IU hMG
Day 6: 100 mg CC + 150–225 IU hMG
Day 15/16: hCG injection
CC: Clomiphene citrate; Gn: Gonadotropin mixtures; GnRHa: Gonadotropin releasing hormone agonist; GnRHant:
Gonadotropin releasing hormone antagonist; hCG: Human chorionic gonadotropin; hMG: Human menopausal
gonadotropin; IU: International units; IVF: In vitro fertilization.
Shrestha D, et al. Ann Transl Med. 2015;3(10):137.
MINIMAL
STIMULATION
PROTOCOL
Day 2/3: 150–225 IU hMG
Day 6: 100 mg CC + 150–225 IU hMG
Day 15/16: hCG injection
GnRH agonist1,2
• Pituitary
desensitization1
• Higher number of
oocytes and viable
embryos, which can be
cryopreserved and used
for FET2
Long protocol
GnRH antagonist1
• Instant blockade of the
pituitary LH secretion
• Shorter duration of the
analog treatment
• Shorter duration of
stimulation with FSH
• Lower risk of developing
OHSS
• Lesser number of daily
subcutaneous injections
required
Short protocol
Minimal stimulation2
• Antiestrogenic effects of
CC suppress the
premature LH surge
• Uses significantly fewer
gonadotropin ampoules than
the agonist protocol
• Low risk of developing OHSS
• Limits daily monitoring visits
and ultrasonography
1. Lambalk CB, et al. Hum Reprod Update. 2017;23(5):560–579. 2. Shrestha D, et al. Ann Transl Med. 2015;3(10):137.
Which are newer
Induction protocols in IVF?
Patients with
repeated IVF
failures
Patients with
poor embryo
quality
Poor
responders
Useful in
challenging
cases
Ultrashort Flare GnRHa/GnRHant Protocol
Orvieto R. J Ovarian Res. 2015;8:69.
COC: Combined oral contraceptive; GnRHa: Gonadotrophin releasing hormone agonist; GnRHant:
Gonadotropin releasing hormone antagonist; LH: Luteinizing hormone; FSH: Follicle stimulating
hormone; hCG: Human chorionic gonadotropin; IVF: In vitro fertilization; OHSS: Ovarian
hyperstimulation syndrome.
Ultrashort Flare GnRHa/GnRHant Protocol
Orvieto R. J Ovarian Res. 2015;8:69.
3 days break
2 days later
Individual program
Follicle size ≥17 mm
COC on cycle days 2–5 for
7 days
0.1 mg GnRHa
0.1 mg GnRHa + FSH only
LH + FSH
GnRHant initiation
Final follicular
maturation
(hCG, GnRHa, or both)
01 Lack of hypoestrogenism
02 Shorter treatment duration
03 Lower gonadotropin requirement
04 Allows cycle programming
05 Protection from severe OHSS
Advantages
Luteal Phase Support in IVF
Need for Luteal Phase Support in IVF
Luteal phase
deficiency
Low
progesterone
levels
Delayed
endometrial
secretory
transformation
Shortened luteal
phase of <10 days
Reduced embryo
implantation
Lower pregnancy rates Increased miscarriage
rates
Cycles resulting from COS, when downregulated with GnRH agonist or
GnRH antagonist, commonly result in luteal phase deficiency.
FET Cycles:
Inevitable Dependence on Exogenous Progestogen
Endometrial changes necessary for implantation
and early pregnancy are totally dependent on
exogenous progesterone supplementation.2
Frozen
embryo
transfer
cycles1,2
No
ovulation
causes an
absence of
endogenous
CL1,2
No
endogenous
source of
progesterone
1,2
1. Mesen TB, et al. Obstet Gynecol Clin North Am. 2015;42(1):135–151. 2. Rashidi BH, et al. Asian Pac J Reprod. 2016;
5(6):490–494.
FET: Frozen embryo transfer; CL: Corpus luteum; hCG: Human chorionic gonadotropin; LH: Luteinizing hormone.
What is the standard LPS protocol in
FRESH AND FROZEN
EMBRYO TRANSFER CYCLES?
Options For Luteal Phase Support In IVF
There are many protocols of luteal
support in IVF cycles.
Luteal phase
support with
progesterone1
Luteal phase
support with
hCG1
Luteal phase
support with
GnRHa1
Standard
approach for IVF
cycles1
OHSS
risk1
1. Karakaş Yılmaz N, et al. Turk J Obstet Gynecol. 2018;15(4):217–221. 2. Rashidi BH, et al. Asian Pac J Reprod. 2016;
5(6):490–494.
GnRHa: Gonadotropin releasing hormone agonist; hCG: Human chorionic gonadotropin; IVF: In vitro fertilization; OHSS: Ovarian hyperstimulation syndrome.
Premature
endogenous LH
surge2
Doses and Routes of Administration of
Progestogens in ART Cycles
30 mg/day
Oral Dydrogesterone1–3
600-800 mg/day
Vaginal micronized
progesterone1
8% (90 mg) once daily
Vaginal progesterone Gel1
50-100 mg/day
Intramuscular progesterone1
FOGSI
Recommendati
on
1. FOGSI position statement on the use of progestogens. Available at: https://www.fogsi.org/fogsi-gcpr/. Accessed on: 28 August 2020. 2.
Tournaye H, et al. Hum Reprod. 2017;32(5):1019–27. 3. Griesinger G, et al. Hum Reprod. 2018;33(12):2212–21.
ART: Assisted reproductive technology; FOGSI: Federation of Obstetric & Gynaecological Societies of India.
Oral Dydrogesterone Is the Right
Progesterone for LPS
Does not suppress the
pituitary–gonadal-axis
at normal therapeutic
doses.1
High selectivity for
progesterone receptors;
hence, minimizes
adverse effects.2
Potent oral progestin
with improved
bioavailability2
Documented evidence
of immunomodulation
that is conducive for
success of pregnancy.3
In India, where 40,000 IVF cycles are performed every year, the oral
route is preferred by the majority of women because they find this
route of administration more convenient.4
Does using a Cocktail Therapy for
LPS Yield Better Results?
Zarei A, et al. Arch Gynecol Obstet. 2017;295(1):239–246.
Vaginal progesterone
Oral dydrogesterone
Combination of oral
dydrogesterone
and GnRH-α
Combination of oral
dydrogesterone
and HCG
No significant
differences between the
four groups regarding
to ongoing pregnancy
rate (p = 0.07) and
miscarriage rate (p =
0.98)
Combination of oral dydrogesterone and GnRH-α or HCG can be
more suitable option compared to vaginal progesterone for LPS in
women with vaginal irritation or discharge at a lower cost.
Combination of Oral Dydrogesterone and GnRH-
α/HCG: A Suitable Option for LPS in FET cycles
In your clinical practice, when do you initiate
Luteal Phase Support in IVF Cycles?
LPS Should Be Initiated Between the Evening
of Oocyte Retrieval and Day 3 After Retrieval
Before oocyte retrieval vs. day of oocyte
retrieval:
PR: 12.9% vs. 24.6% (p=0.01)
Day 6 vs. Day 3 after oocyte retrieval:
PR: 44.8% vs. 61.0% (p=0.05)
Evening of oocyte retrieval vs. Day 2/3
after oocyte retrieval:
No difference in PR
Window of LPS initiation.
The window between the evening
of oocyte retrieval and day 3 after retrieval is the ideal time for initiation of LPS
The timing of luteal phase support initiation can affect the likelihood of pregnancy.
Connell MT, et al. Timing luteal support in assisted reproductive technology: A systematic review. Fertil Steril. 2015;103(4):939–46.
Does the period of initiation differ for
Fresh and frozen embryo transfer?
LPS Initiation in Frozen Embryo Transfer
Extrapolation of luteal support data from stimulated IVF
cycles to FET is not possible due to the absence of a corpus
luteum.1
Lack of functional corpus luteum and absence/suppression of natural
cyclicity in FET cycles2
Micronized E2 is administered in doses of 4–8 mg daily for 12–
14 days until a triple-line endometrium of ≥8 mm thickness is
observed1,3
Progestogen supplementation is then started to prepare
the endometrium for embryo implantation.1–3
1. Casper RF. Fertil Steril. 2014;101(3):627–8. 2. Mesen TB, et al. Obstet Gynecol Clin. 2015;42(1):135–51. 3. Groenewoud ER, et al. Fertil Steril.
2018;109(5):768–74.
For how long do you continue progesterone
supplementation for LPS in
Fresh and frozen Embryo Transfer Cycles?
Evidence Supports Continuation of Luteal Support
Till 12 Weeks of Gestation
Lotus I Trial1
10 mg TID oral dydrogesterone vs. 200 mg
TID MVP till 12 weeks of gestation
Fresh embryo transfer Frozen embryo transfer
Lotus II Trial2
10 mg TID oral dydrogesterone vs.
8% MVP gel (90 mg daily) till 12
weeks of gestation
Rashidi et al.3
20 mg BID oral dydrogesterone vs. 400 mg
BID intravaginal progesterone vs. 50 mg
BID IM progesterone till 12 weeks of
gestation
Zarei et al.4
Vaginal progesterone vs. oral
dydrogesterone vs. oral
dydrogesterone + GnRH vs. oral
dydrogesterone + hCG till 12 weeks
in patients who had positive FHR at
6 weeks.
1. Tournaye H, et al. Hum Reprod. 2017;32(5):1019–27. 2. Griesinger G, et al. Hum Reprod. 2018;33(12):2212–21. 3. Rashidi BH, et al. Asian Pac J Reprod.
2016;5(6):490–4. 4. Zarei A, et al. Arch Gynecol Obstet. 2017;295(1):239–246.
Which is the approved progestogen
for LPS?
The Only Approved Dydrogesterone for
Luteal Support in ART
1. Data on file. 2. New Drugs and Clinical Trials Rules, 2019. Available at: https://cdsco.gov.in/opencms/opencms/Pdf-
documents/NewDrugs_CTRules_2019.pdf. Accessed on: 14 February 2020.
.
Abbott’s dydrogesterone is the only approved
dydrogesterone for luteal support in ART.1
“A drug approved by the Central Licencing
Authority for certain claims and proposed to
be marketed with modified or new claims
including new indication, route of
administration, dosage and dosage form, it
is considered as a new drug for a period
of 4 years from the date of permission
granted by the Central Licencing
Authority.”2
New Drugs and
Clinical Trials
Rules, 2019.
Dydrogesterone: New Drug for Luteal
Support in ART
1. New Drugs and Clinical Trials Rules, 2019. Available at: https://cdsco.gov.in/opencms/opencms/Pdf-
documents/NewDrugs_CTRules_2019.pdf. Accessed on: 14 February 2020. 2. Permission issued in Form 46 to
Abbott India Limited (Data on file).
Abbott’s dydrogesterone is considered as a
New Drug for luteal support in ART.1
Abbott was granted
approval for the
indication ‘luteal support
in ART (IVF)’ for 10 mg
dydrogesterone tablets on
06 April 2018.2
Other manufactures need to
seek permission from the
Central Licencing Authority to
promote dydrogesterone for
luteal support in ART (IVF).2
Key Messages
FET: Frozen embryo transfer; OHSS: Ovarian hyperstimulation syndrome; IVF: In vitro fertilization.
FET not only decreases the risk of OHSS, but also improves
the reproductive outcomes of IVF treatment.
Infertility is a common occurrence in recent times and IVF is
the most successful treatment for infertility.
FET policy should be individualized in line with modern patient
handling approaches.
Oral dydrogesterone is effective in infertile women undergoing
IVF, irrespective of the cause of infertility or the number of
factors contributing to infertility.
IND2158298-2 5th Jan 2021 For the use of registered medical practitioner only
Thank You
D.G.F. Infertility Committee Organise
LIVE WEBINAR Every Month on 20th
Risks of Compounded Stress During IVF
Changes in
sleeping/
eating
patterns
Worsening
of chronic
and mental
health
problems
Stress
and
anxiety
Disturbs the necessary balance of
hormonal conditions required
to become pregnant
Automatic hormonal release elevates
heart rate, increases blood pressure,
and boosts energy
Causes physiological and psychological
damage

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Unlocking I.V.F Services Redefining the New Normal Dr Sharda Jain

  • 1. Unlocking I.V.F Services Redefining the New Normal Dr. Sharda Jain SECRETORY GENERAL D.G.F DIRECTOR LIFECARE CENTRE /LIFECARE IVF
  • 2.
  • 3. Transfer of an embryo into the uterus Culture in laboratory Fertilization of eggs with sperms to create embryos Egg collection under sedation Ovarian stimulation using gonadotropin hormones Sullivan-Pyke CS, et al. Semin Perinatol. 2017;41(6):345–353. 1 in 8 couples experience difficulty in conceiving. In Vitro Fertilization: Unlocking the Key to Infertility IVF
  • 4. Increasing Demand for IVF – A New Paradigm of Parenthood Eskew AM, Jungheim ES. Mo Med. 2017;114(3):156–159. The increasing demand for fertility treatment drives research and development of technologies to optimize IVF regimens and success Maternal Age Genetic relatedness Lifestyle Gestational carriers Genetic abnormalities
  • 5. Which are most popular Investigations in Evaluations prior to IVF?
  • 6. Investigations and Evaluations Prior to IVF: Blood Tests Mutlu MF, et al. J Turk Ger Gynecol Assoc. 2012;13(3):196–203. IVF: In vitro fertilization; FSH: follicle-stimulating hormone; GnRH: Gonadotrophin releasing hormone. Basal serum FSH levels Basal serum estradiol level Basal serum inhibin-B level Anti- Mullerian hormone GnRH stimulation test Exogenous FSH ovarian reserve test 1 2 3 4 5 6 7 Clomiphene citrate challenge test
  • 7. Semen analysis2 + DFI Evaluation of UTERUS 2 • Hysterosalpingogram • Saline infusion sonohysterography • Hysteroscopy • Trial or mock transfer Ultrasonography1 • Ovarian volume • Total ANTRAL FOLLLICLE Counts • Ovarian stromal blood flow Other Investigations and Evaluations Prior to IVF 1. Mutlu MF, et al. J Turk Ger Gynecol Assoc. 2012;13(3):196–203. 2. Society for Assisted Reproductive Technology. Available at: https://www.sart.org/patients/sart-patient- evaluation/#:~:text=The%20uterus%20is%20usually%20evaluated,and%20direction%20of%20the%20uterus. Accessed on: 19 August 2020. Sonographic assessment of OVARIAN RESERVE is advantageous in selecting poor responders and choosing appropriate stimulation protocols at the beginning of the cycle Prior to IVF, a trial or “MOCK” TRANSFER may be done to determine the length and direction of the uterus OR
  • 8. RECOMMENDATIONS on good practices during the current pandemic?
  • 9. Good Practices for Resumption of Reproductive Care SIX PILLARS of good medical practice proposed for the restart of activity in the ART clinic and laboratory are: Discussion, agreement and consent to the start of treatment Staff and patient triage Access to advice and treatment Adaptation of ART services Treatment cycle planning Code of Conduct for staff and patients ART: Assisted reproductive technology. ESHRE guidance on recommencing ART treatments. Available at: https://www.eshre.eu/-/media/sitecore- files/Guidelines/COVID19/ESHRE-Guidance-on-Recommencing-ART-treatments_update- 04052020.pdf?la=en&hash=A584F8A306C570BE7648C167CB190F994E21F05A. Accessed on: 16 August 2020.
  • 10. Discussion, Agreement before the Start Treatment ART: Assisted reproductive technology. ESHRE 16 August 2020. Patients must sign and adhere to the Code of Conduct and agree to discontinue treatment if necessary. Inform patients about the Risk and Prevention of viral infection. High-risk patients should not start ART treatment until permitted by relevant healthcare professionals. Offer the choice of proceeding or postponing ART treatment and document patient preference.
  • 11. Staff Triage and Management STAFF Triage questionnaire 2 weeks prior to the start of clinic activities Start work Occupational health advice & self quarantine Test for antibodies (IgM, IgG) Asymptomatic Triage negative Triage potentially positive Mild/nonspecific symptoms ? + Specific symptoms and/or a previous viral test Triage positive + – Ig: Immunoglobulin; SARS-CoV: Severe acute respiratory syndrome-associated coronavirus. ESHRE 16 August 2020. –
  • 12. Patient Triage and Management Patients Triage questionnair e 2 weeks prior to the start of treatment Include Exclude Be open minded Patients/partners asymptomatic Triage negative Triage potentially positive Mild/nonspecific symptoms ? + Specific symptoms and/or a previous viral test Triage positive + – – Test for antibodies (IgM, IgG) ESHRE 16 August 2020.
  • 13. Adaptation of ART Services is just like any surgery Settings Specific sanitation procedures ART centers to guarantee continuity of treatment provision Limited access, social distancing, Follow-up after 3 weeks of oocyte retrieval and/or embryo transfer, to identify potential virus positive patients ESHRE 16 August 2020.
  • 14. Treatment Cycle Planning Ovarian stimulation monitoring • Minimal exposure for both staff and patients • Minimal number of visits and optimized number of blood tests • Vaginal probe and tissue hygiene Oocyte retrieval • Follow standard procedures unless changes occur between ovulation trigger and oocyte retrieval • If patients tests positive for viral infection , postpone treatment, refer, and isolate • Exceptions for oncology patient or patient at high risk of OHSS Embryo transfer • Limit the number of staff members in the transfer room • Perform transfer only in cases of low risk/asymptomatic patients and partners • Apply freeze-all policy for all patients and/or partners who became symptomatic after the oocyte retrieval Cryopreservation • High security straws and/or vapor phase storage tanks should be used for cryopreservation of samples from virus positive patients ESHRE 16 August 2020.
  • 15. FRESH OR FROZEN EMBRYO TRANSFER: The choice on resumption of practice?
  • 16. Resumption of Infertility Treatment Should Be Under Strict Infection Control Measures COVID-19: Pause Infertility and Reproduction Treatments? Available at: https://www.medicinenet.com/covid- 19_infertility_and_reproduction_treatments-news.htm. Accessed on: 17 August 2020. Diagnostic infertility testing FET and IUI Less invasive procedures Ovarian stimulation, oocyte retrieval and embryo transfer Invasive lengthy procedures The resumption of practice will be done in a stepwise fashion. Strict infection control measures are mandatory during the reopening of practice. FET: Frozen embryo transfer; IUI: Intrauterine insemination.
  • 17. FROZEN EMBRYO TRANSFER Will Be the Choice of Treatment After Resumption of Practice Deferred FET is the best choice for women already on their preparatory phase of ART treatment, which can be as long as several months. Ideal solution for women who cannot postpone their ovarian stimulation without incurring a risk of reducing their chance of success. No compromise regarding overall chance of pregnancy Frozen embryo transfer will be the treatment of choice after resumption of fertility practice. Tesarik J. Reprod Biomed Online. 2020;40(6):760–762.
  • 18. Rationale Behind Success With Frozen Embryo Transfer Embryo transfers are disengaged from ovarian stimulation in the ovarian stimulation cycle.1 Primary objective of FET cycles is adequate preparation of the endometrium to receive the thawed embryos.1 Supraphysiological hormonal levels achieved at the end of COS2 Negatively affect the endometrial receptivity in fresh ET2 Adversely affect implantation rates in fresh ET2 Fresh ET Adverse effects induced by COS disappear in the following cycle2 FET can be successfully performed2 FET FET
  • 19. FET Cycles Are Associated With a Decreased Risk of Low Birth Weight and Preterm Delivery Low birth weight Preterm delivery Small for gestational age Placenta previa, placental abruption Compared to fresh ET, pregnancies resulting from FET are associated with lower risk of:1,2
  • 20. Lets Talk-- in which patient profile is FROZEN EMBRYO TRANSFER most advantageous?
  • 21. Who Would Benefit From the Freeze-All Policy? Patients with an altered endocrine and CV profile Patients at risk of OHSS Patients with inadequate uterine cavity for Embryo transfer Patients who are Hyper- responders Patients undergoing PGT-A at the Blastocyst stage Some probable indications for freeze-all embryo cycles are:1,2 OHSS E+CV ET HR PGT-A
  • 22. FET Is Beneficial in High Responders Acharya KS, et al. Fertil Steril. 2018;110(5):880–887. FET cycles have higher pregnancy rates than fresh transfers in high responders (with 15 or more oocytes retrieved). High responders Intermediat e responders Low responders FET cycles vs. fresh ET cycles  CPR: 61.5 % vs. 57.4%  LBR: 52.0 % vs. 48.9%  CPR: 44.2% vs. 49.6%  LBR: 35.3% vs. 41.2 %  CPR: 15.9% vs. 33.2%  LBR: 11.5% vs. 25.9% Higher after fresh cycle Higher after fresh cycle Higher after FET cycle
  • 23. FET for All Normal Responders? FETs are associated with an increased implantation rate, CPR, and ongoing pregnancy rate. Roque M et al. 2015 study1 Differences in implantation rate and ongoing pregnancy rate were being driven by the higher responders with 10–15 oocytes retrieved. Roque M et al. 2017 study2 Implantation rates Ongoing pregnancy rates Fresh cycle FET Fresh cycle FET Group 1 (4–9 retrieved oocytes) 17.9% 20.5% 31% 33% Group 2 (10–15 oocytes) 22.1% 30.1% 34% 47%
  • 24. Lets talk How can the COMPOUNDED STRESS during the current pandemic affecting an ART Patients ?
  • 25. Risks of Compounded Stress During IVF Changes in sleeping/ eating patterns Worsening of chronic and mental health problems Stress and anxiety Disturbs the necessary balance of hormonal conditions required to become pregnant Automatic hormonal release elevates heart rate, increases blood pressure, and boosts energy Causes physiological and psychological damage
  • 26. Tips to Handle Compounded Stress 05 04 03 02 01 DIGITAL DETOX Use relaxation/mindfulness MEDITATION Collect information from reliable sources like WHO, CDC, ASRM Interact with support groups Self-help books and positive SELF-TALK are powerful
  • 27. Recommendations for reducing the RISK OF VIRAL TRANSMISSION during fertility treatment
  • 28. Recommendations for Reducing the Risk of Viral Transmission Couples proceeding to ART need repeated viral screening to minimize risk of viral transmission to partners and offspring. Samples from viral carriers be processed in a separate laboratory or designated space. Fertility centre should be equipped to treat couples POSITIVE for viral diseases. Pre-conceptional counseling on the risks of sexual and vertical transmission of infections should be provided.
  • 29. The following measures have been proposed to further reduce the risks of CROSS CONTAMINATION of samples in liquid nitrogen storage: Practice Committee of American Society for Reproductive Medicine. Recommendations for reducing the risk of viral transmission during fertility treatment with the use of autologous gametes: A committee opinion. Fertil Steril. 2013;99(2):340–346. Recommendations for Reducing the Risk of Cross Contamination of Samples in IVF Lab Specimen containers should be able to withstand freezing temperatures and thawing cycles Use ‘‘double bagging’’ or sealing techniques to prevent direct contact of cryocontainers with liquid nitrogen Storage of samples in liquid nitrogen vapor ‘‘Sperm-washing’’ to decrease the viral load before freezing semen samples
  • 30. Joint ISAR-IFS-ACE recommendations 22 Dec 2020 on Rresuming ART Services Willingness to start services in a phased manner Sufficient staff, facilities, and consumable s Clear policies on number of cycles/ patients the clinic can handle Fair and scientific approach on making their policies on education and training of staff Willing to triage patients and undertake only patients tested or screened negative as per the existing regional policy Close liaison with another clinic Written code of conduct for patients and staff Arogya Setu app downloaded on patient’s cell phones before start of the treatment a must
  • 31. Patient Selection and Prioritization for Fertility Services Patient selection Patient prioritization to be based on • Avoid high-risk patients • Avoid third-party reproduction, (donor with fresh oocytes and surrogate cycles) • Start ART cycles for fertility preservation in cancer survivors at the earliest • Prefer low-risk cases that would require minimum clinic visits • Impact of delay on patient prognosis • Impact of treatment delay on the mental and emotional well-being of patients Joint ISAR-IFS-ACE recommendations 22 Dec 2020
  • 32. ESHRE GUIDANCE (22 December 2020). on Resuming Fertility Treatments (1/2) More Testing Increased counseling and information to patients planning a pregnancy or already pregnant
  • 33. ESHRE Guidance on Resuming Fertility Treatments (2/2) Decrease the number of patients treated Limit access to treated patient only (no partners) Increase patient and staff triage and testing Limit staff exposure and allow more time between patient appointments Enhance sanitation measures Use PPE intensively Increase the use of telemedicine Avoid embryo transfer and advise a freeze-all strategy to all patients, particularly in high viral–incidence areas Reaffirm the Code of Conduct
  • 34. EMERGENCY MEASURES for Clinics During the Pandemic ESHRE 22 December 2020. Clinics may need to temporarily reduce or even suspend their activity as a result of staff shortages. All ART centers should have agreements with other centers to guarantee continuity of treatment.
  • 35. Recommendations for Centers and Clinicians Centers Clinicians • Monitor epidemiological data. • Monitor internal and external risk factors, which may have an impact on ART services, including but not limited to staff number and availability of supplies. • Consider mitigation measures to reduce these risks. • Inform their patients about the risk of infection before and during pregnancy. • Routine testing of asymptomatic staff and patients (based on service-specific protocols) should be considered
  • 36. ASRM Task Force Guidelines on Resuming Practices 22 December 2020. The impact of delay on patient prognosis due to medical factors, such as age, ovarian reserve, or endometriosis The number of patient visits required The impact of treatment delay on the mental and emotional well-being of patients The impact of delay on patient ability to pursue or access treatment due to insurance coverage or employment status.
  • 37. Vertical transmission of the virus From mother to fetus During the current pandemic?
  • 38. Chances of Vertical Transmission of Virus is Rare Neonates delivered by positive mothers have tested negative for the virus. Evidence for intrauterine infection caused by vertical transmission in late pregnancy is lacking. The consequences of infection among women during early pregnancy is unknown. Although evidence of vertical transmission of is still unclear, it may be POSSIBLE. Mimouni F, et al. J Perinatol. 2020;40(5):820–6.
  • 39. Vertical Transmission of Virus is Rare But Possible Mimouni F, et al. J Perinatol. 2020;40(5):820–6.
  • 40. What are the adapted IVF protocols in the Current Scenario?
  • 41. INDIVIDUALIZATION Of Treatment In IVF La Marca A, et al. Hum Reprod Update. 2014 ;20(1):124–140. Individualization of treatment in IVF Best treatment tailored to patient’s unique characteristics Maximizing the chances of pregnancy Eliminating the avoidable risks resulting from ovarian stimulation PERSONALIZATION OF TREATMENT IN IVF SHOULD BE BASED ON THE PREDICTION OF OVARIAN RESPONSE Normal responders POOR responders HYPER responders
  • 42. Preferred Timing of Initiating Ovarian Stimulation Early follicular phase stimulation Luteal phase and ‘random start’ stimulation Double/dual stimulation (DuoStim) Ovarian stimulation is started any time throughout the cycle. Two stimulations and oocyte retrievals are performed on the same cycle. Ovarian stimulation may be initiated anytime throughout the menstrual cycle Evidence indicates that luteal phase or ‘random start’ stimulation compared to follicular phase stimulation results in: • Significantly higher number of mature oocytes • Top-quality embryos • Higher live birth and ongoing pregnancy rates 39.2% 44.4% 0 5 10 15 20 25 30 35 40 45 50 FPS LPS Timing of ovarian stimulation Ongoing pregnancy and live birth rates p=0.012 Pregnancy outcomes Freeze-all Mizrachi Y, et al. Hum Reprod Update. 2020;26(1):119–36. FPS: Follicular phase stimulation; LPS: Luteal phase stimulation.
  • 43. CC: Clomiphene citrate; Gn: Gonadotropin mixtures; GnRHa: Gonadotropin releasing hormone agonist; GnRHant: Gonadotropin releasing hormone antagonist; hCG: Human chorionic gonadotropin; hMG: Human menopausal gonadotropin; IU: International units; IVF: In vitro fertilization. Shrestha D, et al. Ann Transl Med. 2015;3(10):137. GnRH agonist protocol (Long protocol) GnRH antagonist protocol (Short protocol) Minimal stimulation protocol Day 21 (previous cycle): 0.1 mg GnRHa Day 2: 150–225 IU Gn + 0.1 mg GnRHa Day 15/16: hCG injection Day 2/3: 150–225 IU Gn Day 6: 0.25 mg GnRHant + 150–225 IU Gn Day 15/16: hCG injection Day 2/3: 150–225 IU hMG Day 6: 100 mg CC + 150–225 IU hMG Day 15/16: hCG injection
  • 44. CC: Clomiphene citrate; Gn: Gonadotropin mixtures; GnRHa: Gonadotropin releasing hormone agonist; GnRHant: Gonadotropin releasing hormone antagonist; hCG: Human chorionic gonadotropin; hMG: Human menopausal gonadotropin; IU: International units; IVF: In vitro fertilization. Shrestha D, et al. Ann Transl Med. 2015;3(10):137. MINIMAL STIMULATION PROTOCOL Day 2/3: 150–225 IU hMG Day 6: 100 mg CC + 150–225 IU hMG Day 15/16: hCG injection
  • 45. GnRH agonist1,2 • Pituitary desensitization1 • Higher number of oocytes and viable embryos, which can be cryopreserved and used for FET2 Long protocol GnRH antagonist1 • Instant blockade of the pituitary LH secretion • Shorter duration of the analog treatment • Shorter duration of stimulation with FSH • Lower risk of developing OHSS • Lesser number of daily subcutaneous injections required Short protocol Minimal stimulation2 • Antiestrogenic effects of CC suppress the premature LH surge • Uses significantly fewer gonadotropin ampoules than the agonist protocol • Low risk of developing OHSS • Limits daily monitoring visits and ultrasonography 1. Lambalk CB, et al. Hum Reprod Update. 2017;23(5):560–579. 2. Shrestha D, et al. Ann Transl Med. 2015;3(10):137.
  • 46. Which are newer Induction protocols in IVF?
  • 47. Patients with repeated IVF failures Patients with poor embryo quality Poor responders Useful in challenging cases Ultrashort Flare GnRHa/GnRHant Protocol Orvieto R. J Ovarian Res. 2015;8:69. COC: Combined oral contraceptive; GnRHa: Gonadotrophin releasing hormone agonist; GnRHant: Gonadotropin releasing hormone antagonist; LH: Luteinizing hormone; FSH: Follicle stimulating hormone; hCG: Human chorionic gonadotropin; IVF: In vitro fertilization; OHSS: Ovarian hyperstimulation syndrome.
  • 48. Ultrashort Flare GnRHa/GnRHant Protocol Orvieto R. J Ovarian Res. 2015;8:69. 3 days break 2 days later Individual program Follicle size ≥17 mm COC on cycle days 2–5 for 7 days 0.1 mg GnRHa 0.1 mg GnRHa + FSH only LH + FSH GnRHant initiation Final follicular maturation (hCG, GnRHa, or both) 01 Lack of hypoestrogenism 02 Shorter treatment duration 03 Lower gonadotropin requirement 04 Allows cycle programming 05 Protection from severe OHSS Advantages
  • 50. Need for Luteal Phase Support in IVF Luteal phase deficiency Low progesterone levels Delayed endometrial secretory transformation Shortened luteal phase of <10 days Reduced embryo implantation Lower pregnancy rates Increased miscarriage rates Cycles resulting from COS, when downregulated with GnRH agonist or GnRH antagonist, commonly result in luteal phase deficiency.
  • 51. FET Cycles: Inevitable Dependence on Exogenous Progestogen Endometrial changes necessary for implantation and early pregnancy are totally dependent on exogenous progesterone supplementation.2 Frozen embryo transfer cycles1,2 No ovulation causes an absence of endogenous CL1,2 No endogenous source of progesterone 1,2 1. Mesen TB, et al. Obstet Gynecol Clin North Am. 2015;42(1):135–151. 2. Rashidi BH, et al. Asian Pac J Reprod. 2016; 5(6):490–494. FET: Frozen embryo transfer; CL: Corpus luteum; hCG: Human chorionic gonadotropin; LH: Luteinizing hormone.
  • 52. What is the standard LPS protocol in FRESH AND FROZEN EMBRYO TRANSFER CYCLES?
  • 53. Options For Luteal Phase Support In IVF There are many protocols of luteal support in IVF cycles. Luteal phase support with progesterone1 Luteal phase support with hCG1 Luteal phase support with GnRHa1 Standard approach for IVF cycles1 OHSS risk1 1. Karakaş Yılmaz N, et al. Turk J Obstet Gynecol. 2018;15(4):217–221. 2. Rashidi BH, et al. Asian Pac J Reprod. 2016; 5(6):490–494. GnRHa: Gonadotropin releasing hormone agonist; hCG: Human chorionic gonadotropin; IVF: In vitro fertilization; OHSS: Ovarian hyperstimulation syndrome. Premature endogenous LH surge2
  • 54. Doses and Routes of Administration of Progestogens in ART Cycles 30 mg/day Oral Dydrogesterone1–3 600-800 mg/day Vaginal micronized progesterone1 8% (90 mg) once daily Vaginal progesterone Gel1 50-100 mg/day Intramuscular progesterone1 FOGSI Recommendati on 1. FOGSI position statement on the use of progestogens. Available at: https://www.fogsi.org/fogsi-gcpr/. Accessed on: 28 August 2020. 2. Tournaye H, et al. Hum Reprod. 2017;32(5):1019–27. 3. Griesinger G, et al. Hum Reprod. 2018;33(12):2212–21. ART: Assisted reproductive technology; FOGSI: Federation of Obstetric & Gynaecological Societies of India.
  • 55. Oral Dydrogesterone Is the Right Progesterone for LPS Does not suppress the pituitary–gonadal-axis at normal therapeutic doses.1 High selectivity for progesterone receptors; hence, minimizes adverse effects.2 Potent oral progestin with improved bioavailability2 Documented evidence of immunomodulation that is conducive for success of pregnancy.3 In India, where 40,000 IVF cycles are performed every year, the oral route is preferred by the majority of women because they find this route of administration more convenient.4
  • 56. Does using a Cocktail Therapy for LPS Yield Better Results?
  • 57. Zarei A, et al. Arch Gynecol Obstet. 2017;295(1):239–246. Vaginal progesterone Oral dydrogesterone Combination of oral dydrogesterone and GnRH-α Combination of oral dydrogesterone and HCG No significant differences between the four groups regarding to ongoing pregnancy rate (p = 0.07) and miscarriage rate (p = 0.98) Combination of oral dydrogesterone and GnRH-α or HCG can be more suitable option compared to vaginal progesterone for LPS in women with vaginal irritation or discharge at a lower cost. Combination of Oral Dydrogesterone and GnRH- α/HCG: A Suitable Option for LPS in FET cycles
  • 58. In your clinical practice, when do you initiate Luteal Phase Support in IVF Cycles?
  • 59. LPS Should Be Initiated Between the Evening of Oocyte Retrieval and Day 3 After Retrieval Before oocyte retrieval vs. day of oocyte retrieval: PR: 12.9% vs. 24.6% (p=0.01) Day 6 vs. Day 3 after oocyte retrieval: PR: 44.8% vs. 61.0% (p=0.05) Evening of oocyte retrieval vs. Day 2/3 after oocyte retrieval: No difference in PR Window of LPS initiation. The window between the evening of oocyte retrieval and day 3 after retrieval is the ideal time for initiation of LPS The timing of luteal phase support initiation can affect the likelihood of pregnancy. Connell MT, et al. Timing luteal support in assisted reproductive technology: A systematic review. Fertil Steril. 2015;103(4):939–46.
  • 60. Does the period of initiation differ for Fresh and frozen embryo transfer?
  • 61. LPS Initiation in Frozen Embryo Transfer Extrapolation of luteal support data from stimulated IVF cycles to FET is not possible due to the absence of a corpus luteum.1 Lack of functional corpus luteum and absence/suppression of natural cyclicity in FET cycles2 Micronized E2 is administered in doses of 4–8 mg daily for 12– 14 days until a triple-line endometrium of ≥8 mm thickness is observed1,3 Progestogen supplementation is then started to prepare the endometrium for embryo implantation.1–3 1. Casper RF. Fertil Steril. 2014;101(3):627–8. 2. Mesen TB, et al. Obstet Gynecol Clin. 2015;42(1):135–51. 3. Groenewoud ER, et al. Fertil Steril. 2018;109(5):768–74.
  • 62. For how long do you continue progesterone supplementation for LPS in Fresh and frozen Embryo Transfer Cycles?
  • 63. Evidence Supports Continuation of Luteal Support Till 12 Weeks of Gestation Lotus I Trial1 10 mg TID oral dydrogesterone vs. 200 mg TID MVP till 12 weeks of gestation Fresh embryo transfer Frozen embryo transfer Lotus II Trial2 10 mg TID oral dydrogesterone vs. 8% MVP gel (90 mg daily) till 12 weeks of gestation Rashidi et al.3 20 mg BID oral dydrogesterone vs. 400 mg BID intravaginal progesterone vs. 50 mg BID IM progesterone till 12 weeks of gestation Zarei et al.4 Vaginal progesterone vs. oral dydrogesterone vs. oral dydrogesterone + GnRH vs. oral dydrogesterone + hCG till 12 weeks in patients who had positive FHR at 6 weeks. 1. Tournaye H, et al. Hum Reprod. 2017;32(5):1019–27. 2. Griesinger G, et al. Hum Reprod. 2018;33(12):2212–21. 3. Rashidi BH, et al. Asian Pac J Reprod. 2016;5(6):490–4. 4. Zarei A, et al. Arch Gynecol Obstet. 2017;295(1):239–246.
  • 64. Which is the approved progestogen for LPS?
  • 65. The Only Approved Dydrogesterone for Luteal Support in ART 1. Data on file. 2. New Drugs and Clinical Trials Rules, 2019. Available at: https://cdsco.gov.in/opencms/opencms/Pdf- documents/NewDrugs_CTRules_2019.pdf. Accessed on: 14 February 2020. . Abbott’s dydrogesterone is the only approved dydrogesterone for luteal support in ART.1 “A drug approved by the Central Licencing Authority for certain claims and proposed to be marketed with modified or new claims including new indication, route of administration, dosage and dosage form, it is considered as a new drug for a period of 4 years from the date of permission granted by the Central Licencing Authority.”2 New Drugs and Clinical Trials Rules, 2019.
  • 66. Dydrogesterone: New Drug for Luteal Support in ART 1. New Drugs and Clinical Trials Rules, 2019. Available at: https://cdsco.gov.in/opencms/opencms/Pdf- documents/NewDrugs_CTRules_2019.pdf. Accessed on: 14 February 2020. 2. Permission issued in Form 46 to Abbott India Limited (Data on file). Abbott’s dydrogesterone is considered as a New Drug for luteal support in ART.1 Abbott was granted approval for the indication ‘luteal support in ART (IVF)’ for 10 mg dydrogesterone tablets on 06 April 2018.2 Other manufactures need to seek permission from the Central Licencing Authority to promote dydrogesterone for luteal support in ART (IVF).2
  • 67. Key Messages FET: Frozen embryo transfer; OHSS: Ovarian hyperstimulation syndrome; IVF: In vitro fertilization. FET not only decreases the risk of OHSS, but also improves the reproductive outcomes of IVF treatment. Infertility is a common occurrence in recent times and IVF is the most successful treatment for infertility. FET policy should be individualized in line with modern patient handling approaches. Oral dydrogesterone is effective in infertile women undergoing IVF, irrespective of the cause of infertility or the number of factors contributing to infertility. IND2158298-2 5th Jan 2021 For the use of registered medical practitioner only
  • 68. Thank You D.G.F. Infertility Committee Organise LIVE WEBINAR Every Month on 20th
  • 69. Risks of Compounded Stress During IVF Changes in sleeping/ eating patterns Worsening of chronic and mental health problems Stress and anxiety Disturbs the necessary balance of hormonal conditions required to become pregnant Automatic hormonal release elevates heart rate, increases blood pressure, and boosts energy Causes physiological and psychological damage