Tips & tricks in endometriosis

Treatment of severe adenomyosis prior to Assisted Reproductive Techniques (ART)

Edgardo SOMIGLIANA, MD-PhD Fondazione Ca’ Granda, Ospedale Maggiore Policlinico

& Università degli Studi di Milano Milan, Italy

Conflicts of interest

Personal conflicts:

Those related to private practice

Conflicts of the referring ART Unit

Financial supports during the last three years received

from Ferring, Merck-Serono, IBSA and MSD

Adenomyosis prior to ART

Endometriosis

Age

Adenomyosis Pregnancy

Adenomyosis prior to ART

v  Abnormal uterine bleeding

v  Repetitive implantation failure

Pre-ART treatment: available evidence

Surgery GnRH agonists Progestins

RCTs

Prospective controlled

Retrospective controlled

Case reports / case series

Retrospective patient-preference study

Frozen-thawed embryo replacement

GnRH agonists (2 months) + HRT versus HRT

Women informed about possible ↑ effectiveness but also ↑ time and costs

339 cycles in women with adenomyosis (US diagnosis) Niu et al., 2013

Pre-ART treatment: comparative studies

GnRH agonists for adenomyosis Ultralong + HRT HRT

Characteristics n=194 n=145 p Age (years) 32.1 ± 4.0 31.5 ± 4.0 ns BMI (Kg/m2) 21.5 ± 3.0 20.7 ± 2.6 ns Previous pregnancies 82 (42%) 57 (39%) ns Duration of infertility (months) 39 ± 19 42 ± 20 ns Serum FSH (IU/ml) 7.5 ± 2.3 7.2 ± 1.3 ns Indication to IVF ns Tubal 79 (41%) 52 (36%) Male factor 53 (27%) 39 (27%) Endometriosis 15 (8%) 10 (7%) Mixed 47 (24%) 44 (30%)

Niu et al., 2013

GnRH agonists for adenomyosis

Ultralong + HRT HRT Characteristics n=194 n=145 p

Endometrial thickness (mm) 9.7 ± 1.4 11.6 ± 1.7 0.04

N. Embryos transferrred 2.0 ± 0.4 1.9 ± 0.4 ns

Implantation rate 127 (33%) 45 (16%) <0.01

Clinical pregnancy rate 100 (52%) 36 (25%) 0.04

On-going pregnancy rate 90 (46%) 31 (21%) 0.02

Niu et al., 2013

Adenomyosis prior to ART

Endometriosis

Age

Adenomyosis Pregnancy

Sallam et al., 2006

OR=4.28 (95%CI: 2.00-9.15)

Ultralong protocol for endometriosis

De Ziegler et al., 2010

*

CPR per pick (%)

Oral contraceptive pre-IVF

Ultralong protocol for endometriosis

Clinical pregnancy: RR=0.72 (95%CI: 0.55-0.95)

Vercellini et al., 2014

Long protocol for adenomyosis

Long protocol: RR=1.05 (95%CI: 0.75-1.48) Short protocol: RR=0.58 (95%CI: 0.38-0.88)

Vercellini et al., 2014

Long protocol for adenomyosis

Surgery for adenomyosis

Retrospective patient preference study

65 women with unexplained infertility > 3 years

28 treated surgically (15 also received GnRH analogues for 6 months)

37 treated with GnRH analogues for 6 months

Outcome: natural pregnancy Wang et al., 2009

Surgery for adenomyosis

Surgery (n=28) GnRHa (n=37) p

Age (years 34.3 ± 2.1 32.7 ± 1.4 0.007

Infertility (years) 3.9 ± 0.9 3.4 ± 0.6 0.04

Max. uterine diameter (mm) 102 ± 9 98 ± 7 ns

Pregnancies (at 3 years) 13 (46%) 4 (11%) 0.002

Deliveries (at 3 years) 9 (32%) 3 (8%) 0.02

Wang et al., 2009

Conclusions

GnRH agonists may increase the chance of pregnancy in women with adenomyosis

Long protocol should be first considered for fresh cycles in women with adenomyosis

Ultralong protocol (or progestins?) prior to fresh or frozen embryo transfer if: v  Abnormal uterine bleeding v  Repetitive implantation failure v  Very severe sonographic findings

Surgery in skilled hands and for adenomyomas if the other approaches failed

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