Endometriosis and subfertility

Key contents
Medical management of endometriosis is often contraceptive.

In contrast, surgical treatment may improve the chance of spontaneous conception.

There is conflicting evidence as to whether surgery improves outcomes with assisted conception, and this should be discussed with a specialist in reproductive medicine.

Surgery, particularly for ovarian endometriosis, can cause a decreased ovarian reserve
and fertility preservation should be considered.

• in the UK is approximately 10%
• in women with subfertility it increases to 25–50%.
  Historically, it was thought that the
  endometrial tissue embedded in the pelvis through retrograde menstruation.
• however, this does not explain the presence of endometriosis found outside of the pelvis.
  Anatomical Distortion
  Up to 30% of women with endometriosis have tubal pathology (obstruction, adhesions or hydrosalpinx).
  However, even women with mild endometriosis have lower fertility rates, suggesting this mechanical barrier to pregnancy cannot be the whole picture.
  ENDOMETRIOMAS

1. OXIDATIVE STRESS
2. CORTICAL STROMA REDUCTION
3. Smoth Muscles METAPLASIA
4. FOLLICLE MATURATION REDUCE(>3 cm)
5. FOLLICULAR ATRESIA
6. IMPAIRED VASCULARITY
7. AMH AND AFC GOES DOWN
   Nearly 30% of endometriomas recur in the 2–5 years after surgical treatment.
   Most of these recurrences (81%) occur in the treated ovary, with 8% recurring in
   both ovaries and 11% in the contralateral ovary.
   ENDOMETRIOISS AND THE OOCYTE EMBRYO
   Using the donor oocyte model to assess the impact of endometriosis on oocyte
   quality, studies have shown a reduced implantation rate when oocytes from
   women with endometriosis have been implanted into a woman without
   endometriosis.

An abnormal mitochondrial structure and reduced mitochondrial mass.

A study that added peritoneal fluid from women with endometriosis to the culture media
of mature mouse oocytes found the oocyte cytoskeleton was significantly altered
and demonstrated increased rates of chromosomal misalignment
No studies have demonstrated a higher rate of aneuploidy in those with endometriosis.

Frozen embryo>>preterm birth/LBW/Preeclampsia/PGT analysis can be
done/Fetal macrosomia

Follicular fluid(+IL6,+p4,)(-cortisol, -ILGFBP)
Granulosa cells express(tnf alpha,soluble fas ligand)
Peritoneal inflammation(inflammatory,proteolytic,angiogenic)-Il,VEGF,cytokines)
Luteinized unruptured follicular syndrome,luteal phase insufficiency,recurrent MC
Endometrial receptivity-integrins,osteopontins
ENDOMETRIAL RECEPTIVITY
T HELPER CELL,Nk CELL,B CELL >>CHRONIC INFLAMMATION,P450 ARMOATASE
EXPRESSION HIGH>REDUCES RECEPTIVITY
integrins,osteopontins
Investigating endometriosis-related subfertility
BaselineIx-USS,AMH/AFC assessment,Ix for ovulatory disorder,tubal factor,semen
analysis
(ESHRE) guideline39 recommends that laparoscopy is no longer the gold
standard.
As highlighted by the current ESHRE guidelines, imaging in the form of magnetic
resonance imaging (MRI) and advance USS are considered as first-line
investigations for DE.

Staging and scoring endometriosis
1.rASRM (ovary/peritoneum superficial deep
endometriosis,ovary/tube filmy/dense adhesions
More than 40 stage 4 endometriosis
2.ENZIAN(rASRM+deep endometriosis)
3.EFI endometriosis fertility index

Management of endometriosis-related subfertility
involve a multidisciplinary team, including a gynaecologist with expertise in the
treatment of endometriosis, a colorectal surgeon, a urologist, specialist nurses
and input from a fertility specialist.

ESHRE guidance is that ovarian suppression should not be prescribed to improve
subfertility related to endometriosis.
Therefore, post-operative medical therapy should not be prescribed with the
intention of improving fertility but rather reserved for post-operative pain
management in women that may not be seeking to conceive
immediately after surgery, with the knowledge that this is not detrimental.
MINIMAL/MILD ENDOMETRIOSIS
ESHRE recommend that laparoscopy could be offered as a treatment for
endometriosis-related subfertility for early-stage endometriosis, as it improves the
rate of ongoing pregnancy.
MODERATE/SEVERE ENDOMETRIOSIS
1.The benefit of excision surgery for symptomatic relief in women with severe
endometriosis has been shown to last for up to 4 years post-surgery.
Pregnancy rates following excision of deep endometriosis with and without bowel
involvement have been reported to be around 20–30% and 50%,
ESHRE guidance is that surgery for deep endometriosis does not definitely
improve fertility but may be an option in symptomatic women wishing to conceive.

Management of endometriomas in the context of subfertility

1.A review of eight prospective observational studies found that the pregnancy
rate following surgical treatment of endometrioma was not significantly different
to other treatment (ART, surgery combined with ART, and aspiration/sclerotherapy
and ART).
2.One study proposed is the 3-stage excision (laparoscopic cyst drainage,
followed by GnRH agonist downregulation, with a repeat laparoscopy to excise the
cyst capsule)
3.ESHRE recommends that where surgery is undertaken, cystectomy should be
performed to reduce the risk of recurrence.

Assisted conception in the context of endometriosis

1.Minimal/mild endometriosis appears to have no impact on clinical pregnancy
rate or live birth rate. By contrast, the presence of moderate/severe endometriosis
significantly lowers the number of eggs collected and reduces live birth rate by
nearly one quarter
2.Intrauterine insemination (IUI) is a less invasive form of assisted conception tha
could be considered in women with minimal or mild endometriosis, after they
have tried to conceive for 1 year, or those in a same sex relationship where
donor sperm is indicated
.
3.Therefore, IUI with ovarian stimulation could be offered as a treatment option, if
all other factors (ovarian reserve, maternal age, patent tubes, semen quality) were
Favourable.

ART and ovarian stimulation for women with endometriosis

1.AMH and AFC have been shown to be reliable predictors of ovarian response to
controlled ovarian stimulation.
Minimal/mild -agonist protocol
Moderate /severe-no difference in protocols
2.When undergoing IVF, women with severe endometriosis may require almost
double the dose of gonadotrophins and achieve lower numbers of oocytes.
Whether altering the ovarian stimulation protocol improves ART outcomes has
been evaluated in several studies. In general, these studies show no difference in
pregnancy rate or live birth rate when using either an agonist or antagonist
protocol.
3.separated minimal/mild endometriosis from moderate/severe endometriosis
found that there was a tendency towards a higher live birth in women with mild
endometriosis using the agonist protocol (42.8% versus 26.7%). In women with
moderate/severe endometriosis there was no difference between the two
protocols

Surgical treatment of endometriosis prior to ART

1.In patients with endometriomas ≥30 mm, endometrioma size was the most
influential contributor to the number of oocytes collected an untreated
endometrioma and women who underwent laparoscopic treatment of
endometriomas prior to ART found no difference in live birth per embryo
transferred (23.7% versus 26.1%, p = 0.80).94 Importantly, cystectomy is
associated with poorer response to stimulation and greater risk of cycle
cancellation compared with no surgery
2.Due to the potential negative impact on ovarian reserve, and no evidence of
increasing live birth rate,routinely operating on endometriomas prior to ART is not
recommended. However, surgery may be considered if the patient is experiencing
pain or to allow access to the follicles at egg collection
3.Expert advice is to offer surgical excision of DE for pain symptoms and patient
preference. In symptomatic women with a history of failed IVF then disease
excision could be considered.
Surgery-30%reduction of ovarian reserve/2.4%risk of POI

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