INNOVATION IN FERTILITY TREATMENT

Prof. Ariel Revel

WHAT IS INNOVATION?

„INNOVATION IS STAYINGRELEVANT.“

- Stephen Shapiro

SURGERY AND INFERTILITY

Laparoscopy• Endometriosis- endometrioma.• Hyd ros a lp inx .

Hysteroscopy• Adhesions.• Polyps.• Myomectomy.• Septum.

PARADIGMIVF outcomes are far superior to those achieved with tubal surgery especially in the setting of large hydrosalpinges visible by ultrasound.

22 April 2019

Diagnostic laparoscopy as a last diagnostic resort, following at least three failed IVF attempts.

HYDROSALPINX

WHEN YOU’RE A HAMMER EVERYTHING LOOKS LIKE A NAIL

SURGICAL CORRECTION OF HYDROSALPINX BEFORE IVF INCREASE EFFECTIVENESS:

In the era of blastocyts ET, PGT-A Is there a better option that salpingectomy or PTO for patients with hydrosalpinx?

DIAGNOSIS

AUTHORS’ CONCLUSIONS LAPAROSCOPIC SALPINGECTOMY SHOULD BE CONSIDERED FOR ALL WOMEN WITH HYDROSALPINGES PRIOR TO IVF TREATMENT

16%30%

37.5% 19%

Johnson N, van Voorst S, Sowter MC, Strandell A, MolBWJ. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation.Cochrane Database of Systematic Reviews,2010

19%37, 5%

AGAINST SURGERY

• Reduction of Ovarian response.• Salpingectomy does not cause significant reduction in ovarian

response [Kotlyar JMIG 2017].

• Complications of laparoskopy.

• Cost.

• Preventing chance of natural conception.

Tsiami, Ultrasound Obstet Gynecol, 2016

Conclusions

Proximal tubal occlusion, salpingectomy and aspiration for treatment of hydrosalpinx scored consistently better than did no intervention for the outcome of IVF-ET.

ESSURE INSERTION FOR HYDROSALPINX

• Infertility 2 – 14 years.

• Age 27 – 41 years.

• Had undergone 5. 4 (range, 1 – 21) IVF cycle attempts.

• 6 patients who had previously failed laparoscopic attempts to block the tubes because of severe bowel adhesions were included in the study.

Before

• Of the 24 patients undergoing a total of 42 IVF cycles after Essure insertion:• 18 (75% of patients and 42.8% of

IVF cycle attempts) conceived • and 16 delivered live births (66.6%

of patients and 38.1% of IVF cycle attempts).

After

ESSURE – RANDOMIZED TRIAL, NOT AS GOOD AS SALPINGECTOMY

The ongoing pregnancy rates per patient according to the intention-to-treat principle were 11/42 (26.2%) after hysteroscopic proximal occlusion by intratubal devices (intervention group) versus 24/43 (55.8%) after laparoscopic salpingectomy (control group) (P = 0.008) [absolute difference: 26.1%; 95% confidence interval (CI): 0.5–51.7, relative risk (RR): 0.56; 95% CI: 0.31–1.03, P = 0.01].

Dreyer, Hum Reprod 2016

ASPIRATION

• 11% of pts in the aspiration group had reaccumulation of hydrosalpinges fluid detected by U/S in just 2–3 days at the time of ET. Fouda, BMC women health, 2015.

•Mostly relevant when hydrosalpinx detected during stimulation and patient insisted on fresh ET.

SCLEROTHERAPY

• Ethanol 98%.

• Ethanol 95% / tetracycline 5%.

•Volume of ethanol instillation - equal to half of the initial aspirated hydrosalpinx fluid and left for 5 to 10 minutes inside the tube.

JMIG, 2018

PATHOGENESIS OF HYDROSALPINX

•Mechanical flushing of the embryos from the uterine cavity.

•Decreased endometrial receptivity.

•Direct embryotoxic effect [practice comm, Fertil steril, 2015].

ENDOMETRITIS

• 1/3 patients with RIF have chronic endometritis.

• 1st line doxycykline.

• 2nd line metronidazole.

• Cumulative (3 ET) in the treated group vs the non CE RIF group was significantly higher (39% vs 28%, p<0.05), [Kitaya, Am J Reprod Immunol. 2017].

99% cure on repeated endometrial biopsy

Toxic primary inflammatory cytokines as interleukin-8 (IL-8), interleukin-2 (IL-2), interleukin-α (IL-α), tumor necrosis factor-α (TNF-α) and prostaglandins existing in hydrosalpinx fluid are the factors that disrupt normal physiology of the endometrium [Jastrow, Fertil Steril2002].

ELECTRON MICROSCOPY

Patient with hydrosalpinx After salpingectomy

Sampaz, ultrastructural pathology, 2019

Cheng, Int J Clin Exp Med. 2015

• PI higher.• Trend for less triple line pattern.• Same thickness.

ENDOMETRIAL SONOGRAPHY PTS WITH HYDROSALPINX

DOXYCYCLINE

• One study has identified an association between biomarkers of chronic endometrial inflammation in the presence of a communicating hydrosalpinx [Bao, Rev Assoc Med Bras, 63 (2017)].

• One retrospective study suggested that extended use of doxycycline before and after an IVF procedure for patients with a hydrosalpinx may minimize the detrimental effect of hydrosalpinges [Hurst, fertil steril2001].

HYSTEROSCOPY TO DETECT ENDOMETRITIS

Normal uterine cavity Chronic endometritis

IS IT TIME TO RECONSIDER?

Blastocyst• Less affected by flushing?• Less uterine contractility at time of blastocyst ET compared to earlier transfer.• Transferring an embryo near the time of implantation may well reduce the

potential of an embryotoxic effect of hydrosalpinx fluid on the embryo.• The relatively large number of cells in a healthy blastocyst likely makes it less

susceptible to toxins than a 4 or 8-cell embryo.

Frozen cycles• No fluid accumulation.• Survival after blastocyst vitrification is high, and the implantation and live-birth

rates are comparable with the transfer of fresh or vitrified single blastocyst embryos.

Endometrial biopsy• Could we determine normal receptive endometrium?

COST/BENEFIT ANALYSIS

• What is your blastocyst transfer pregnancy rate?• Does hydrosalpinx have such –ve effect on pregnancy rate like day 3 embryo?

• Does patient perform PGT A?

• Is patient paying out of pocket?• For surgery?• For IVF?

• Complication risk of surgery.• Overall incidence of bowel injury in gynecologic laparoscopy was 1 in 769

[Murray, Fertil steril, 1998].

TAKE HOME MESSAGE

• Improvement in IVF results may have reduced the negative impact of hydrosalpinx.

• In some cases patients with hydrosalpinx can be counseled not to undergo surgery before IVF.

• More research is needed to reevaluate the hydrosalpinx paradigm.

QUESTIONS?

arielrevel2@gmail.com