Frozen Embryo Transfer Cycles-Sarhan

Frozen Embryo Transfer Cycles
ABDULMAGID SARHAN
MD, FRCOG
ZAGAZIG UNIVERSITY
Frozen Embryo Transfer Cycles, SARHAN

INTRODUCTION
❑ First successful pregnancy following FET was performed by
Trounson and Mohr, (1983).
❑ With significant improvements in cryopreservation technology
(vitrification), the number of frozen ET IVF cycles is increasing
and may surpass in numbers and success rates those of fresh cycles

INTRODUCTION
❑ Cryopreservation of embryos has become an integral part of ART
programs.
❑ Increased dramatically
▪ Trend towards transferring fewer embryos after a fresh IVF cycle
▪ Improved laboratory techniques

INTRODUCTION
Factors affecting the success rate of FET cycles:
❑ Quality of the frozen embryo
❑ The stage of the embryo at freezing
❑The survival rate after thawing
❑ The number of embryo transferred
❑ Storage duration
❑ The technique of the operator.

INTRODUCTION
Factors affecting the success rate of FET cycles:
The stage of the embryo at freezing
❑ Cleavage stage embryos with grade I or II, and present ≥6 blastomeres
at D3 are the right kind.
❑ Embryos with 4 blastomere: continue in vitro culture to reach the stage of 8
blastomere then perform vitrification cryopreservation.
❑ Non-high quality embryos: continue to culture them into blastocyst and select the
valid blastocyst for cryopreservation.

Endometrial Preparation Protocols


Optimal Endometrium Preparation for FET cycles Has utmost
importance for insuring the best outcome and demands:
❑ Different endometrial preparation protocols.
❑ Progesterone Support
❑ Identification of receptive window of implantation for ET.

1-Natural Cycles
True / Modified
2-Ovulation induction
CC, Nolvadex, Letrozole or HMG or a combination.
3-Programmed (Artificial) Cycles
E and P
GnRHa, E and P

Natural Cycles
❑ Need regular cycles and proven ovulation.
❑ Involves frequent monitoring of urine and/or blood LH levels,
early luteal P levels, and U/S monitoring of the developing
dominant follicle.
❑ Optimal FET results need precise identification of the LH surge.

Natural Cycles
Method
1- D10-12 <3-5 days prior to estimated ovulation day>
* Serial US: E thickness, follicular development and to time the
commencement of testing for LH.
* LH (urine or blood) for detecting of the LH surge.
* Progesterone levels.
2- US for evidence of ovulation

Natural Cycles
Method.
3- * The day of ovulation corresponds to the day of egg retrieval.
* If the embryo were frozen at day 3: ovulation day + 3 is the
right time to transfer.
4- LPS with Progesterone

Natural Cycles
Advantages:
❑ Preferable to many women.
❑ No medications are used.
❑ Endocrine preparation of the endometrium is achieved by
endogenous sex steroid production from a developing follicle
Disadvantages:
❑ Identification of LH surge is difficult.
❑ Ovulation may not always occur even in regular menstrual cycle.

Modified Natural Cycle
❑ To overcome the disadvantages of LH monitoring “ Administering
HCG to initiate luteinization”
❑ Involve U/S monitoring of the developing follicle, measurements
of the endometrial strips, and monitoring of serum hormonal levels
followed by 5000 - 10000 IU of HCG when the dominant follicle is
>17mm and P level is low.

Modified Natural Cycle
Advantages:
❑ Less U/S evaluation due to the HCG administration compared
with true NC-FET
Disadvantages:
❑ Unexpected ovulation
❑ Difficult in ensuring timely ET.

Ovulation Induction Cycles

❑ In patient with their ovary functional but anovulatory and
irregular cycles
❑ Ovulation may be induced by
❑ CC,
❑ Nolvadex,
❑ letrozole
❑ hMG or
❑ a combination
❑ For synchronization the day of HCG administration should
correspond to the day HCG administration of the source cycle in
which the embryos were retrieved

❑ Letrozole is the 1st choice for endometrial preparation for FET.
❑ Dose of 2.5-5mg from D3 to D7 and administration of HCG when
the follicles reach the criteria of maturity.
❑ ET after 4-5 days for embryos frozen at 72hr and after 6-7 days
for the blastocyst embryo.
❑ Progesterone Supplement

❑ Clomiphine Citrate (CC)
❑ Start D 3 to 5 of menstruation or withdrawal for 5 days
❑ E2, 2mg/d until D of HCG administration to overcome
detrimental effect of CC on endometrium.
❑ HCG (10000 IU)
❑ Repeated testing of P with US
❑ adequate follicular size (18-22 mm) and
❑ E thickness ≥8mm:

How to calculate the Day of Embryo Transfer?
Method:
FRESH IVF CYCLE hCG -1 0PU D1 D2 D3 D4 D5 D6
-2 0
True natural cycle LH surge
Modified natural cylce hCG
Artificial cycle Progest
Ovulation induction hCG

Programmed (Artificial) Cycles

❑ To mimic the endocrine exposure of the endometrium in the
normal cycle.
❑Involve suppression of natural menstrual cycle with or without the
use of GnRH agonist.
❑This require
❑exogenous E for the proliferation of the endometrium, while suppressing the
developing dominant follicle.
❑P replacement to achieve adequate secretory changes in the endometrium.

❑ An endometrial thickness > 7 mm and showing triple line is
favorable for ET.
❑ The endometrium is affected by either incremental or fixed E
levels, even in supraphysiologic range.

❑ Endometrial development is unaffected by the length of the
follicular phase.
❑ No adverse effects of reduction the duration of exposure to E to
6 days or an increase up to 35 days.
❑ However receptivity is best preserved when the follicular phase is
kept between 12 and 19 days.

Method:
❑ Estrogen administration on D2 or 3 of cycle by either incremental or fixed
levels [3 tab] until the endometrial thickness on U/S has reached approximately
8mm and then add progesterone for the numbers of days proportional to the
stage of development of the embryo being transferred.
❑ ET
❑ If you are freezing on D3 Morula: transfer on day 4 of progesterone.
❑ If freezing on D5 Blastocyst: transfer on day 6 of progesterone.
❑Not the duration of E2 supplementation but the endometrium thickness should be the
leading factor in determining the start of progesterone
❑ LPS
❑ Estrogen and progesterone.

Method:
❑ Estrogen administration on D2 or 3 of cycle by either incremental or fixed
levels [3 tab] until the endometrial thickness on U/S has reached approximately
8mm and then add progesterone for the numbers of days proportional to the
stage of development of the embryo being transferred.
❑ ET
❑ If you are freezing on D3 Morula: transfer on day 4 of progesterone.
❑ If freezing on D5 Blastocyst: transfer on day 6 of progesterone.
❑Not duration of E2 supplementation but the endometrium thickness should be the leading
factor in determining the start of progesterone
❑ LPS
❑ Estrogen and progesterone.

Method:
-2 0

Method:
❑ Using GnRHa in Programmed Cycles is to suppress temporarily
ovarian function, thus ensure the prevention of luteinization that
may occurs when using E&P alone (about 5%)

Advantages:
❑ Greater control and flexibility in the timing of transfer.
❑ Cycles are easier to plan: popular among many patients and their
doctors.
❑ The length of the follicular phase can be varied without detriment
to IR or PR
❑ Cycle cancellation rate is low.
❑ It is the most convenient with respect to limited monitoring
requirements and ease and flexibility of scheduling.
❑ It is the best method for patient with irregular cycles.

Disadvantages:
❑ The administration of E and P does not guarantee complete
pituitary suppression: a dominant follicle may occur. luteinization
may occur in 5%
❑ Should the follicle undergo spontaneous luteinization,
endometrium may be exposed to progesterone earlier with
incorrect timing of thawing and transferring.

Disadvantages:
❑ GnRHa co-treatment may be used to downregulate the pituitary
and prevent follicular growth and this may be less ‘physiological’.
❑ Programmed (artificial) cycles have not been shown to be superior
to properly timed natural or modified natural FET cycles.

Progesterone Supplementation In FET cycles
LPS:
❑ If a pregnancy occurs, E and P must be continued until placental
autonomy is established to replace the absent corpus luteum.
❑ No difference in PR between different methods of LPS in patients
undergoing ‘fresh’ IVF or ICSI
❑ The use of synthetic progesterone compared with natural
progesterone.??

❑ The optimal form of Progesterone supplementation has not been
established.
❑ Patients preference and convenience, as well as costs should be
considered when choosing either vaginal or IM P preparations.

❑ It has been well documented in elegant pharmacological studies
that absorption of Progesterone into the endometrium is superior
with the vaginal P compared with IM P administration, whereas
higher serum P levels are measured after the injections.

❑Traditionally higher serum P levels were presumed to be better for
the FET outcomes. However, recent studies showed that increasing
IM P doses to achieve higher serum levels does not translate into
improved outcomes.
❑ High P levels (>20ng/ml) on the day of transfer of single euploid
blastocysts were associated with lower ongoing PRs and lower live
birth rates.

CONCLUSION
✓ No significant advantage of one specific approach to
prepare the endometrium for FET in terms of PR or
LBR.
✓It is not possible, to recommend one endometrial
preparation method in FET over another.

CONCLUSION
✓Choice for either NC or AC should be made based
upon other factors:
✓hospital and IVF laboratory settings
✓ patient or doctor preference.
✓Performance of previous cycles
✓ number of hospital visits to plan FET
✓possible serious adverse events and side-effects

Method:
-2 0


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Frozen Embryo Transfer Cycles

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

Frozen Embryo Transfer Cycles, SARHAN

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