The document summarizes new guidelines from ESHRE (European Society of Human Reproduction and Embryology) regarding monitoring of IVF cycles and prevention of OHSS. Key points include: 1) Adding estradiol or hormonal panel measurements to ultrasound monitoring is probably not recommended for monitoring cycles based on evidence showing no improvement in efficacy or safety. 2) Triggering final oocyte maturation based on estradiol level or estradiol to follicle ratio is not recommended, as no studies have assessed use of these criteria. 3) For patients at high risk of OHSS, a GnRH agonist trigger followed by LH supplementation is recommended to reduce risk, and a freeze-all strategy is

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What is new in
ESHRE Guidelines, 2019
 Monitoring of IVF cycle
 Prevention of OHSS
Prof. Aboubakr Elnashar
Benha university Hospital, Egypt
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR

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 Recommendation
 Strong
Most individuals should receive the intervention
 Conditional
 different choices is appropriate
 you must help each patient arrive at a
management decision consistent with his or her
values and preferences
 GPP
Good practical point
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR

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 Certainty of the evidence (GRADE)
⨁⨁⨁⨁ HIGH
⨁⨁⨁◯ MODERATE
⨁⨁◯◯ LOW
⨁◯◯◯ VERY LOW
 High quality:
 We are very confident that the true effect lies close to that of the
estimate of the effect
 Moderate quality:
 We are moderately confident in the effect estimate: The true effect is
likely to be close to the estimate of the effect, but there is a
possibility that it is substantially different
 Low quality:
 Our confidence in the effect estimate is limited: The true effect may
be substantially different from the estimate of the effect
 Very low quality:
 We have very little confidence in the effect estimate: The true effect
is likely to be substantially different from the estimate of effect
ABOUBAKR ELNASHAR
A. OVARIAN RESPONSE TESTING
B. LH SUPPRESSION&OVARIAN STIMULATION
C. MONITORING
D. TRIGGERING OVULATION&LUTEAL SUPPORT
E. PREVENTION OF OHSS
ABOUBAKR ELNASHAR

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3. In COS for fertility preservation in oestrogen sensitive
diseases the concomitant use of anti-oestrogen therapy,
such as letrozole or tamoxifen, is probably
recommended.
 Conditional ⊕
 The existing literature concerning controlled ovarian
stimulation for fertility preservation in women with oestrogen
sensitive cancer is limited by its observational nature, small
patient numbers and relatively short duration of follow-up.
Despite these limitations, both letrozole and tamoxifen
protocols may be safe
ABOUBAKR ELNASHAR
C. MONITORING
ABOUBAKR ELNASHAR

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1. The addition of E2 measurements to US monitoring
is probably not recommended.
 Conditional ⊕⊕
 Based on the evidence, monitoring using E2 &US is not
superior to monitoring by US alone in terms of
 efficacy&
 safety
ABOUBAKR ELNASHAR
2. The addition of a hormonal panel consisting of a
combination of E2, progesterone& LH measurements to
US monitoring is probably not recommended.
 Conditional ⊕
 According to one RCT, monitoring using hormonal panel
assessments (E2, LH, P) & US not superior over
monitoring by US alone in terms of
 efficacy
 safety.
ABOUBAKR ELNASHAR

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3. Routine monitoring of endometrial thickness
during COS is probably not recommended.
 Conditional ⊕
 There are indications that thin endometrium is related to
lower CPR
 Thin endometrium is infrequent (2-5%).
 Interventions to correct thin EMT have
 little rational basis&
 should be abandoned until contrary evidence arises.
ABOUBAKR ELNASHAR
 The guideline group suggests performing a single
measurement of the endometrium during US
assessment on
 day of triggering or
 oocyte pick-up
 To counsel patients on potential lower pregnancy
chance.
 GPP
 A single US assessment is necessary to identify patients with very thin or very thick EMT,& appropriate diagnostic work-up should be done.
ABOUBAKR ELNASHAR

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4. Criteria for triggering:
1. Follicular size:
 The association of follicle size as a triggering criterion with outcome has not been sufficiently studied.
 individualized. Case by case basis
 Conditional ⊕⊕
ABOUBAKR ELNASHAR
 The decision on timing of triggering in relation to
follicle size is multi-factorial, taking into account the
1. Size of the growing follicle cohort
2. Hormonal data on the day of pursued trigger
3. Duration of stimulation
4. Patient burden, financial costs
5. Experience of previous cycles
6. Organizational factors for the center.
 GPP
ABOUBAKR ELNASHAR

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 Most often, final oocyte maturation is triggered at
 sizes of several of the leading follicles
 between 16-22 mm.
 GPP
ABOUBAKR ELNASHAR
2. E2 level:
is not recommended to base timing of final oocyte
maturation triggering.
 Strong ⊕
 No study has been performed assessing the use of E2 as a criterion for
when to trigger final oocyte maturation.
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 E2 levels during OS vary depending on
1. size of the growing follicular cohort
2. distribution of follicles between different size classes within
the growing cohort
3. endocrine situation of the patient
4. endocrine milieu of the stimulation cycle.
 The association of E2 with
 clinical outcomes&
 OHSS risk
 has been studied in several observational studies, but
management recommendations cannot be derived from
these observational data.
ABOUBAKR ELNASHAR
3. E2/follicle ratio.
is not recommended to base timing of final oocyte
maturation.
Strong ⊕
 The association of E2-to-follicle ratio with clinical outcomes has
been studied in observational studies, but recommendations
cannot be derived from these observational data.
 E2-to-follicle ratio will vary depending on
 size of the growing follicular cohort
 distribution of follicles between different size classes
 endocrine situation of the patient
 endocrine milieu of the stimulation cycle.ABOUBAKR ELNASHAR

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5. Criteria for cycle cancellation
 Poor response to COS alone is not a reason to
cancel a cycle.
 Strong ⊕
 For low responders, PR may be low but not absent.
 Counsel patients individually regarding
 pregnancy prospects
 decision to continue this or further treatment.
ABOUBAKR ELNASHAR
 The physician should counsel the individual poor responder
regarding pregnancy prospects& decide individually whether to
continue this and/or further cycles.
 Reported pregnancy rates among poor responders to ovarian
stimulation differ between 0 – max reported 18%. These differences
could be explained by the exact number of oocytes retrieved, as well as
the age of the patient and indication for treatment. Although pregnancy
rates may be low, they are not absent per se.
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 In GnRHa cycles with an ovarian response of ≥18
follicles, there is an increased risk of OHSS&
preventative measures are recommended, which
could include cycle cancellation.
 Strong ⊕
 Regarding a high response there are also no solid criteria to cancel a cycle.
 A high response identifies women most at risk for OHSS.
 Therefore, preventive measures are recommended which could include cycle cancellation.
ABOUBAKR ELNASHAR
5. GnRHa bolus, in addition to progesterone for LPS in
hCG triggered cycles can only be used in the context of
a clinical trial
 Current evidence indicates higher live birth /pregnancy rates
with GnRH agonist bolus in addition to progesterone, repeated
GnRH agonist infections alone or in addition to progesterone
for LPS.
 Limited evidence suggests that GnRH agonist for LPS does
not increase the risk of OHSS.
 However, long-term health effects in the new-born have not
been studied.
 Until these data are available, the GDG recommends to use
GnRH agonist for LPS only in the context of clinical trials.
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 Repeated GnRHa injections, alone or in addition to
progesterone for LPS in hCG triggered cycles can
only be used in the context of a clinical trial
ABOUBAKR ELNASHAR
6. Addition of LH to progesterone for LPS can only be
used in the context of a clinical trial
 No conclusions can be drawn on the effect of LH
supplementation for LPS from the available evidence, and this
intervention cannot be recommended.
ABOUBAKR ELNASHAR

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E. PREVENTION OF OHSS
ABOUBAKR ELNASHAR
1. Prior to start of COS, a risk assessment for high
response is advised.
 GPP
 High risk:
 PCOS
 An above average ovarian reserve status
 High ovarian response as indicated by
 Follicle number at US
 High E2 levels, or
 High number of oocytes obtained
 Applying the freeze-all strategy implies the presence of a high-quality cryopreservation
program.
ABOUBAKR ELNASHAR

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2. Antagonist protocol is recommended for
 PCOS women with regards to improved safety&
equal efficacy.
Strong ⊕⊕
 Predicted high responders with regards to
improved safety & equal efficacy.
 GPP
 if GnRHa protocols are used, reduced GnT dose is
recommended to decrease the risk of OHSS.
 Conditional ⊕
ABOUBAKR ELNASHAR
3. GnRHa trigger
 is recommended for final oocyte maturation in
women at risk of OHSS.
 Strong ⊕
 Triggering final oocyte maturation with GnRHa significantly
reduces the risk of early-onset OHSS
 GnRHa trigger should be followed by LPS with LH-
activity (hCG or LH)
 Conditional ⊕
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 GnRHa trigger
 is preferred over HCG in
 patients at risk of OHSS
 cases where no fresh transfer is performed.
 Conditional ⊕
 Evidence from RCTs performed in oocyte donors indicates that GnRHa
trigger is preferable over hCG when freeze-all is applied.
ABOUBAKR ELNASHAR
 GnRHa trigger
 is preferred over coasting strategy in
patients at risk of OHSS.
with or without a freeze-all strategy
 GPP
 The two most relevant studies were both on retrospective data, with inherent
methodological and risk of bias problems.
 Therefore, the GDG cannot recommend coasting and hCG trigger over GnRHa
trigger for final oocyte maturation.
ABOUBAKR ELNASHAR

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 When GnRHa trigger is used
Cabergoline or albumin as additional preventive
measures for OHSS are not recommended.
 GPP
ABOUBAKR ELNASHAR
4. Freeze-all strategy
 recommended to eliminate the risk of late-onset
OHSS
 applicable in both GnRHa & GnRHan protocols.
Strong ⊕⊕⊕
 The current evidence suggests that freeze all lowers the
OHSS risk, without completely eliminating the condition.
 The latter urges for follow up of haemo-concentration status
even in cases with the freeze-all strategy applied.
ABOUBAKR ELNASHAR

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ABOUBAKR ELNASHAR
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