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Case Scenarios in ART
1. Case Scenario in ART
Moderators
• Sujoy Dasgupta
• Suparna Banerjee
Panelists
• Abhishek Daga
• Amitoj Athwal
• Manisha Bajaj
• Ratna Chattopadhyay
• Rohit Gutgutia
• Sanjoy Mukherjee
• Sunita Sharma
2.
3. Case Scenario 1
• Mrs BD, 26 yr- irregular
cycle since menarche
• BMI 30 Kg/M2
• HSG and semen
analysis- normal
• Ultrasound-
4. Line of management?
• Weight loss
• Ovulation induction
• Insulin sensitizers
How?
Any specific target?
Which agent?
How long?
Follicular tracking?
Metformin?
Inositol?
5. Weight reduction
• BMI <27 kg/m2 for women trying to conceive
(NICE, 2013).
• “SMART” (sustainable, measurable,
achievable, realistic and timely) goal (ESHRE,
2018).
• 5-10% weight loss can have positive impact
6. Ovulation Induction- CC vs Letrozole
• Letrozole is considered as the first line of agent
in PCOS (ACOG, 2018; ESHRE, 2018).
• The PPCOS II (Pregnancy in PCOS) trial-
better pregnancy and live birth rates than CC (Legro
et al., 2014)
• More favourable molecular markers of
implantation in the endometrium than CC
(Mehdinejadiani et al., 2019; Miller et al., 2012; Ganesh et al., 2014).
• Less incidence of multiifollicular development
(Franik et al., 2018; Teede et al., 2018).
7. Monitoring of OI cycle
• CC cycle- to see response and risk of OHSS
(NICE, 2013)
• Letrozole- risk of multiple pregnancy 3-7%
(Fritz and Speroff, 2011).
• HOMP recorded with letrozole (Warraich and Vause,
2015).
• Midluteal serum progesterone – limited role
• TVS should be done in the first cycle of
Letrozole.
8. Metformin
Modest reduction in
weight
NOT recommended as appetite suppressant
(Morley et al., 2017)
Metformin + CC •May increase ovarian response to CC (NICE,
2013; Vandermolen et al., 2001; Hwu et al., 2005)
•The PPCOS I trial- Live birth rates
1. CC alone 22.5%
2. Metformin alone 7.2%
3. CC and Metformin 26.8% (Legro et al., 2007).
Metformin + Letrozole No Data
Metformin +
Gonadotropin
Significantly reduces the risks and severity of
OHSS (Huang et al., 2015; Palomba et al., 2013).
Consider Metformin For OVERWEIGHT PCOS, especially if NOT
responding to CC (ESHRE, 2018)
9. Inositol
• Combination of D-chiroinositol and
myoinositol- 40:1 ratio- improves ovulation
(Formuso et al., 2015; Monastra et al., 2017; Facchinetti et al., 2015).
• Use of inositol in PCOS should be considered
“experimental”, although some studies
showed promising results (ESHRE, 2018)
10. Mrs BD now reduced weight
• Current BMI 26 kg/m2
• Taken letrozole 5 mg/day for OI
• No dominant follicle developed
• Next step?
11. If letrozole does NOT work?
• Try CC?
• Add insulin sensitizers?
• Try Gonadotropin?
• Advise LOD?
Evidence for CC if letrozole
does not work ?
hMG versus rFSH?
Any specific precautions?
To do or not at all?
Pre-operative evaluation?
Specific surgical precaution?
12. Gonadotropin in PCOS
• Second line of agent for women resistant to oral agents (NICE,
2013; ESHRE, 2018).
• Risk of OHSS and multiple pregnancy
• Step up regimen, starting with lower dose (37.5 to 75 IU/day)
and gradually increasing the dose
• Intense monitoring
• Trigger with hCG ONLY if 1-2 mature follicles (ESHRE, 2018).
• Theoretically- demerit of hMG- contains LH
• Meta-analysis- rates of ovulation, pregnancy, miscarriage, live
birth and OHSS- similar between FSH and hMG- (Weiss et al.,
2015).
13. Laparoscopic Ovarian Drilling (LOD)
• Second line of treatment as the
alternative to gonadotropin (NICE, 2013;
ESHRE, 2018).
• Commonly 3-6 punctures are done in
each ovary, avoiding the tubal-
ovarian interface
• Post-op spontaneous ovulation rate 40-
90% and 50% of them conceive (Fritz
and Speroff, 2011)
• Less incidence of multiple pregnancy
and OHSS
• Does not require extensive monitoring
• Anaesthetic risks, risk of adhesion
formation and POF (Lepine et al.,
2017; ESHRE, 2018).
• Should have serum LH >10 IU/L
and BMI <30 kg/m2 (Fritz and
Speroff, 2011).
• Systematic review- LOD was
NOT superior to gonadotropin
therapy in terms ovulation and
pregnancy rates (Farquhar et al.,
2012).
14. Mrs BD underwent LOD
• Subsequently responded to letrozole
• Taken 8 cycles of letrozole
• Failed to conceive
• Now wants to do IUI
16. Level 1 ART Clinic
• Preliminary investigations including diagnosis of
type, cause of infertility
• Only IUI is carried out as part of treatment.
• An application for registration shall be made by
the ART Clinics to the Appropriate Authority in
duplicate, in Form 3
• Application fee of: Rs 1,00,000
• Minimum staff requirement
01 Gynecologist with qualifications with at least 3
years of experience on Reproductive Medicine
01 Counselor with qualifications as specified
18. Cycle day Tablet
Letrozole
Injection
hMG
Right Ovary Left Ovary Endometrial
thickness
D2 2.5 mg AFC 20 AFC 18 5 mm
D3 2.5 mg
D4 2.5 mg
D5 2.5 mg
D6 2.5 mg
D7 75 IU
D8 75 IU
D9 75 IU
D10
D11 14/2
13/2
12/5
14/3
11/2
7.5 mm
IUI stimulation started for Mrs BD
19. What to discuss with Mrs BD?
1. Proceed for IUI and add antagonist
2. Cancel IUI cycle and ask abstinence from
intercourse
3. Conversion to IVF
20. Cancellation versus conversion
• Discuss pros and cons of each option- cost
implications
• Risks of OHSS/ multiples are high if
1. Serum estradiol levels >900–1,400 pg/mL
2. >4-6 follicles ≥10–14 mm
3. >3 follicles ≥15 mm (ACOG, 2017; ESHRE, 2018).
21. Mrs BD Decided to convert to IVF
• Antagonist (Inj
Cetrorelix 0.25 mg/day)
added
• Inj hMG continued at
150 IU/day dose
• Trigger done with Inj
Triptoreline 0.2 mg
• 35 hr after trigger, OPU
was done
• 12 oocytes retrieved
• Husband- Mr PS
collected semen
• Previous semen
analysis-
Normozoospermia
• Today- 1-2 motile
sperms/hpf
Explanation?
Remedy?
22. Possible reasons of sudden abnormal
semen parameters
• Significant intra-individual variability (10.3-26.8%
(Alvarez et al., 2003).
• Laboratories not adhering to WHO standards (Penn et al.,
2010; Keel et al., 2002)
• Testicular heat exposure 3 months back (e.g., fever)
(WHO, 2010)
• Inadequate sexual stimulation can affect semen
quality (van Roijen et al., 1993)
24. Decision for ICSI was taken for Mrs
BD
• 4 good quality
blastocysts on day 5
• Fresh or frozen
embryo transfer?
• Endogenous hCG tends
to make OHSS more
severe and prolonged
(ASRM, 2016; RCOG, 2016)
• GnRh Agonist trigger
causes LPD (Humaidan et
al., 2011)
25. Discharge-advice after OPU?
• Analgesics
• Antiemetics
• Cabergoline
• High protein diet
• Adequate fluid intake
• Contact immediately if
1. Severe nausea/
vomiting
2. Severe pain
3. Breathlessness
4. Reduced urine output
5. Unusual symptoms
(s/o VTE)
26.
27. Case Scenario 2
• Mrs AC, 33-yr-old
woman having regular
cycles
• Trying for pregnancy for
3 years
• c/o severe and
progressively increasing
dysmenorrhoea and
dysparaeunia
• TVS-
28. Line of management?
• Laparoscopy
• IVF, embryo freezing
and then consider
laparoscopy
• IVF only
• Hormonal therapy for 3
months, then reevaluate
Cystectomy/ Drainage?
Counselling before
surgery?
Dienogest
GnRH agonists
29. Factors to decide the mode of
treatment?
• Ovarian reserve- Age,
AMH, AFC
• Semen parameters
• Tubal patency
• Severity of symptoms
• Past surgery
• Previous fertility
treatment
• Patient’s wishes
Mrs AC
Age 33, AMH- 2.5 ng/ml,
AFC- 8+10
Normozoospermia
Tubes not yet checked
Pain not responded to
NSAID
No previous surgery
Received 6 cycles of
letrozole for OI
Relief of pain and wants to
conceive
30. Endometriosis and Subfertility
Hormonal Suppression
• Clinicians should NOT
prescribe ovarian
suppression treatment to
improve fertility
• Most of the hormone
therapies will prevent
pregnancy
• Ovarian suppression does
NOT improve subsequent
ovarian response (ESHRE,
2022)
Surgery
• Still controversial if
cumulative pregnancy rate is
more after surgery but time
to achieve pregnancy was
significantly shorter (ESHRE,
2022)
31. Surgery for Endometriosis-
Subfertility
rASRM stage I/II
endometriosis
Operative laparoscopy could be offered
Improves the rate of ongoing pregnancy.
Endometrioma Operative laparoscopy may increase their
chance of natural pregnancy
No data from comparative studies exist
Cystectomy >> Drainage/coagulation
Possible decline in ovarian reserve
Deep
endometriosis
No compelling evidence exists
Operative laparoscopy may represent a treatment
option in symptomatic patients wishing to conceive
(RCOG, 2017; NICE, 2017; ESHRE, 2022)
32. Mrs AC underwent laparoscopy
• Right Ovarian 5 cm
chocolate cyst
removed
• Severe adhesion in
POD- complete
adhesiolysis was
done
• Dye test B/L positive
33. After laparoscopy- Attempt of
natural conception or IVF?
• Women should be counselled
of their chances of becoming
pregnant after surgery.
• To identify patients that may
benefit from ART after
surgery, the Endometriosis
Fertility Index (EFI) should
be used as it is validated,
reproducible and cost-
effective.
• The results of other fertility
investigations such as their
partner’s sperm analysis
should be taken into account
(ESHRE, 2022)
36. What should be the post-operative
treatment plan?
• Counselling?
• Ovarian suppression
after surgery?
Chance of recurrence
Better not to delay
pregnancy
Women seeking pregnancy
should NOT be prescribed
postoperative hormone
suppression with the sole
purpose to enhance future
pregnancy rates (ESHRE, 2022)
37. Mrs AC is now pain-free
• Visited 4 doctors over the period of next 2
years.
• Received different brands of letrozole for
ovulation induction- total 12 cycles
• She wants to do IUI
38. ESHRE, 2022
rASRM stage I/II
endometriosis
•May perform IUI with ovarian
stimulation, instead of expectant
management or IUI alone
•IUI+OS increases pregnancy rates.
rASRM stage III/IV
endometriosis
•The value of IUI in women with tubal
patency is uncertain
•IUI +OS could be considered
Can IUI be done in endometriosis?
39. Hughes, 1997 Meta-analysis- IUI success is halved in stage I/II
endometriosis
Gandhi et al., 2014 No difference between expectant management and IUI
Dmowski et al., 2002 First-cycle chance of pregnancy with IVF is
significantly higher than the cumulative pregnancy rate
after 6 IUI cycles
Van der Houwen et al., 2014;
D’Hooghe et al., 2006
The risk of endometriosis recurrence appears to be
increased by IUI (more than IVF)
IVF, but not IUI, can be expected to overcome the
detrimental effects of a pelvic inflammatory milieu.
Limitations of IUI in endometriosis
40.
41. Finally Mrs AC (now 35) decided for
IVF
• TVS- B/L
endometrioma
(6 cm in right side, 4 cm
left side)
• Next plan?
1. IVF directly?
2. Laparoscopy before
IVF?
Severity of pain
Serum AMH
Scan finding-
1. Accessibility of the
follicles
2. AFC
42. Mrs AC has no pain, AMH 0.9 ng/ml,
AFC 4+3
In infertile women with
endometrioma > 3 cm only
consider cystectomy prior to
ART to improve
1. endometriosis-associated
pain or
2. the accessibility of
follicles (ESHRE, 2022)
Concern about
endometrioma puncture
during OPU?
• In women with
endometrioma, clinicians
may use antibiotic
prophylaxis at the time of
oocyte retrieval, although
the risk of ovarian abscess
following follicle
aspiration is low (0-1.9%)
(ESHRE, 2022, RCOG 2017)
43. RCOG Scientific Impact Paper (2017)
Directly ART
• Asymptomatic women,
• women of advanced
reproductive age,
• those with reduced
ovarian reserve,
• B/L endometriomas,
• a history of prior ovarian
surgery
Surgery before IVF
• Highly symptomatic
women,
• with an intact ovarian
reserve,
• unilateral and large cysts,
• cysts with suspicious
radiological and clinical
features.
43
44. IVF protocol for Mrs AC?
• Any specific IVF
stimulation protocol?
• Pretreatment COC/
Progesterone?
• No specific protocol can be
recommended.
• Both GnRH antagonist and agonist
protocols can be offered based on
patients’ and physicians’ preferences
as no difference in pregnancy or
live birth rate has been
demonstrated
• Insufficient evidence to recommend
prolonged administration of the
COC/progestogens as a pre-treatment
to ART to increase live birth rates
(ESHRE, 2022)
45. Down regulation with GnRH agonist depot?
• The administration of GnRH agonists for a period of
3-6months prior to IVF or ICSI in women with
endometriosis increases the odds of clinical
pregnancy by 4-fold.
46.
47. Paradigm Shift?
ESHRE, 2013 ESHRE, 2022
• Clinicians can prescribe
GnRH agonists for a period
of 3 to 6 months prior to
treatment with ART to
improve clinical pregnancy
rates in infertile women
with endometriosis
• The extended administration
of GnRH agonist prior to
ART treatment to improve
live birth rate in infertile
women with endometriosis
(ultralong protocol) is no
longer recommended due
to unclear benefits.
48. How does endometriosis affect
oocytes and embryos?
• Ooplsm- “dark cytoplasm,"
"and "diffused cytoplasmic
granularity.“ (Rienzi et al.,
2011).
• Oocytes with degenerative
signs (Ayse et al., 2014).
• Altered oocyte morphology,
abnormal mitochondrial
content (Sanchez et al., 2017).
• Altered follicular fluid
molecules (VEGF, IL-6)
(Garrido et al., 2000).
49. Does endometriosis affect IVF
success?
• Recent Meta-analysis- Endometriosis does NOT
affect embryo quality (Dongye et al., 2021).
• ESHRE database- No difference in IVF outcome
between endometriosis and other fertility issues
(Dunselman et al., 2014).
• Systematic review- stage I and II endometriosis, the
pregnancy rate was similar to that in tubal infertility,
although in stage III and IV endometriosis, the
pregnancy rate was significantly poor (Barnhart, et al.,
2012).
50.
51. Case Scenario 3
• Mrs BG, 28-yr old
• Trying for pregnancy for only 5 months
• Already received letrozole and dydrogesterone
for 4 months (no follicular monitoring)
• Semen, AMH, HSG- all investigations done
and all are normal
52. Can this be labeled as “Unexplained
Subfertility”?
• Unexplained subfertility
is usually diagnosed if a
couple fails to conceive
after 1 year of regular
unprotected sexual
intercourse even though
investigations for
ovulation, tubal patency
and semen analysis are
normal
53. Mrs BG is very anxious to conceive
What’s the next step?
• Continue further cycles of OI with letrozole
• Change OI regime- CC/ Gonadotropin
• Advise IUI
• Counsel for IVF
• Explain facts and figures and ask to try naturally for few
cycles (NICE, 2013)
Age (years) Pregnant after 1 year (12 cycles) % Pregnant after 2 years (24 cycles) %
19–26 92 98
27–29 87 95
30-34 86 94
35-39 82 90
54. Mrs BG changed the doctor
• She came back after 3
years
• Meanwhile she tried
multiple cycles of OI with
letrozole, CC and
gonadotropins
• What’s next step?
Laparoscopy?
IUI?
Rationale?
IVF?
“Only treatment”?
55. • Meta-Analysis
• Success rate of IVF - ∼25% (NNT- 4)
*European IVF-Monitoring Consortium (EIM) for ESHRE, 2016
Jacobson et al., 2010 Duffy et al., 2014
OR for ongoing pregnancy (95% CI) 1.64 (1.05– 2.57) 1.94 (1.20–3.16)
The number of infertile women that
should undergo destruction of
superficial peritoneal endometriosis
12 8
The prevalence of grade I/ II
endometriosis among women with
unexplained infertility
≤50%
NNT 24 16
Laparoscopy in Unexplained
Infertility
57. NICE, 2013- “IVF is the ONLY treatment for
Unexplained Subfertility after 2 years”
• Based on a single RCT (Bhattacharya et al., 2008)
• Increases “unnecessary” IVF (Woodward et al., 2016)
• NICE recommendation - proper utilization of NHS funding is
important to get the maximum benefits for fertility treatment
(Chambers et al., 2012).
• No such funding in India
• Many trusts in the UK- provide OS with IUI with reasonable
good success rate (Nandi and Homburg, 2016).
• A recent large retrospective study- IUI is more cost-effective
than IVF in improving the live birth rate (Bahadur et al., 2020).
58. Other side of the Atlantic
• The treatment of unexplained infertility is by necessity
empiric.
• For young women, the best initial therapy is a course
(typically 3 or 4 cycles) of ovarian stimulation with oral
medications and OS-IUI followed by IVF
59. IUI in unexplained subfertility
• Bypasses cervical factors
• Deposits good number of motile spermatozoa near
the tubes
• Overcomes “improper” coital techniques
• “Superovulation” leads to release of >1 egg and
improves the follicular development
60. Treatment as per age and duration
of infertility
(Nandi and Homburg, 2016)
61. Mrs BG finally decided for IVF
• Benefits of IVF in
unexplained
infertility?
• Evaluation of oocyte
quality
• Evaluation of embryo
quality
• Bypasses subtle tubal
dysfunction
• IVF Itself can be
diagnostic
(Nandi and Homburg, 2016).
62. IVF cycle of Mrs BG
• Antagonist protocol with r-FSH 150 IU/day for
11 days
• hCG Trigger
• Semen sample good
• 16 oocytes obtained
• Conventional IVF done
• Day1- Total fertilization failure (TFF)
63. She wants to know whether ICSI
could have been useful for her?
Nandi and Homburg, 2016 No reported difference in clinical pregnancy and
live-birth rates between IVF with ICSI in unexplained
infertility
Canadian fertility and
Andrology Society, 2019
Insufficient evidence to recommend the routine
addition of ICSI to increase the live birth rate (Level
1B)
ASRM, 2020 ICSI has been associated with higher fertilization
rates and a reduced risk of TFF as compared to
conventional IVF
Song et al., 2021 ICSI does not improve live birth rates but yields
higher cancellation rates than conventional IVF in
the treatment of unexplained infertility.
64.
65. Case 4
• Mrs PM, 20 years, trying for pregnancy for 1
year
• Cycles regular, no dysmenorrhoea
• AMH 2.9 ng/ml
66. Is this semen analysis “Abnormal”?
Volume 2 ml
Colour Whitish
Viscosity Normal
Liquefaction Time 45 minutes
pH 7.6
Sperm Concentration 18 million/ ml
Total Motility 42%
Progressive Motility 17%
Non progressive Motility 25%
Immotile 58%
Normal Morphology 5%
Abnormal Morphology 95%
Vitality 62%
Round cells Nil
68. Precautions before interpreting HSG
• Spasm of the smooth muscles of the tube → “false”
impression of “fallopian tube block” (Suresh and Narvekar,
2014)
• In 40-60% cases of B/L proximal block diagnosed in
HSG, at least one tube may be found open on further
investigations (repeat HSG, SSG, laparoscopy)
(Hajishafiha et al., 2009; Verhoeve et al., 2010; Foroozanfard and Sadat, 2013)
69. Options for Mrs PM?
• Laparoscopy?
• IVF?
• Noninvasive options?
Lap dye test alone?
Additional procedure?
Implication of ART bill?
Repeat HSG
Sonosalpingography
(SSG)
Hysterosalpingo-Contrast-
Sonography (HyCoSy)
71. Noninvasive options
Repeat
HSG
• After premedication with antispasmodics
• 60% cases initially “blocked” tubes were found open
(Dessole et al., 2000)
• Increased risk of radiation exposure and hypothyroidism
(Hart et al., 2009)
SSG • Relatively simple procedure, no radiation exposure (Suresh
and Naverkar, 2014, Maheux-Lacroix, 2014)
• Assesses uterine cavity, myometrium and the ovaries
• In 70-80% at least one tube is found open by SSG
(Hajishafiha, 2009; Lanzani, 2009)
• Can avoid both laparoscopy and IVF
HyCoSy • Delineates exact site of block (Luciano, 2011)
• Expensive, not easily available
• Meta-analysis-HyCoSy NOT superior to SSG (Maheux-
Lacroix, 2014)
72. Decisive factors for IVF vs
laparoscopy?
• Age of the woman
• Ovarian reserve
• Sperm parameters
• Number of children desired
• Site and extent of the tubal disease
• Risk of ectopic pregnancy
• Risk of OHSS
• Success rates of IVF programme
• Cost- Financial burden- “two
consecutive medical procedures to
achieve parenthood”
• Expertise of the surgeon
• Patient’s preferences
(Suresh and Narvekar, 2014; ASRM, 2015)
SSG of Mrs PM - no spill in POD
73. Hysteroscopic Tubal Cannulation
Type of study Authors Successful
cannulation
Concepti
on rates
Ectopic
pregnancy
Case series Ikechebelu et
al., 2018
90.2% per tube and
88.9% per patient
33.3% Nil
Case series Chung et al.,
2018
67.0% per tube and
71.4% per woman
55%
Cohort study Mekaru et al.,
2011
25.9% per tube and
37.1% per patient
30.77% 7.69%
Meta-analysis Honore et al.,
1999
85% per tube tube 48.9% 9.2%
• Proximal tubal obstruction
• Young women
• No other significant infertility factors (NICE, 2013; ASRM, 2015)
74. Mrs PM underwent laparoscopy
• No adhesion
• Tubal cannulation done
successfully
• Tubal patency was
confirmed B/L
• She came back after 4
years
• Now she is 24
• She underwent several
cycles of OI and 3
cycles of IUI
75. Mrs PM wants to know why she
cannot conceive naturally
• Tubal patency ≠ normal function of the tube
(Approbato et al., 2020; Tan et al., 2018; Luca et al., 2017)
• All possible explanations for “unexplained
subfertility”
76. Mrs PM now decided for IVF
• Antagonist protocol,
hMG 225 IU/day x 10
days
• On the day of OPU
Husband failed to
produce semen
How to tackle this
situation?
Can this situation be
avoided?
77. Semen collection problem is NOT
uncommon
• 8.3% of the men experienced ejaculation-
failure on the day of operation for ART (Li et al.,
2016).
• Only 59% of the men attending the fertility
clinic felt comfortable in masturbation and
48% required external stimulation to collect
semen (Pottinger et al., 2016).
80. Explanation to the patient?
Causes of poor egg quality
1. Age
2. Endometriosis
3. Obesity
4. Smoking
5. Chemotherapy
6. Past ovarian surgery
7. Improper stimulation protocol
81. Oocyte maturation is required to complete meiosis and
to produce a competent oocyte (MII), able to sustain
embryo development, implantation and pregnancy.
Hakan C et al., 2012
MII
82. Day3- single grade B embryo
Fresh embryo transfer was done
• Beta-hCG negative
• The couple then decided for egg donation
83. Oocyte Donor- ART-Bill, 2022
• ART banks
• An insurance coverage for a period of 12 months in favor
of the oocyte donor by the commissioning couple
• For Oocyte Donors AADHAR card no. to be entered
• Bank shall supply the sperm or oocyte of a single donor to
ONLY one commissioning couple.
• An oocyte donor shall donate oocytes only once in her life
• Not >7 oocyte shall be retrieved from the oocyte donor.
• Donor age- 23-35
84. Mrs PM conceived after egg
donation
• Singletone pregnancy
• She wants to do Down
Syndrome Screening
Any special measures?
85. Aneuploidy Screening after oocyte
donation
• Risk calculation should be based on the age of
the donor (biological mother), NOT the
recepient (Sahraravand and Ryynanen, 2010; Bonnin et al., 2017)
The specific question of GnRH agonist pre-treatment has been addressed in an older Cochrane review (Sallam, et al., 2006) that – based on three included studies in a total of 228 patients – concluded that prolonged downregulation for 3–6 months with a GnRH agonist in women with endometriosis increases the odds of clinical pregnancy by more than 4-fold.
In contrast, the updated version of this Cochrane review (Georgiou, et al., 2019), including 8 parallel-design RCTs involving a total of 640 participants, concluded that the effect of GnRH agonist pre-treatment (for at least 3 months) was very uncertain, both on live birth rate as primary outcome, as well as on secondary outcomes (clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, mean number of oocytes and mean number of embryos). All studies included in this review have compared long-term GnRH agonist versus no pre-treatment. The authors acknowledged the very low quality of data, particularly for reporting live birth rate. Compared to the previous version of the review, the outcome of live birth now includes only one new unpublished trial (NCT01581359) and excludes a previously included RCT (Dicker, et al., 1992) as this paper does not truly report on live birth as per the definition of the international glossary on infertility and fertility care (Georgiou, et al., 2019). For the outcome of clinical pregnancy rate (CPR), the review includes three new RCTs, leading to the results being closer to the line of no effect.
In light of the paucity and very low quality of existing data, particularly for the primary outcomes examined, further high‐quality trials are required to definitively determine the impact of long‐term GnRH agonist therapy on IVF/ICSI outcomes, not only compared to no pretreatment, but also compared to other proposed alternatives to endometriosis management