OPTIMISING IUI RESULTS – ENDOSCOPIC SURGERY

Dr. Sudha Tandon
Gynaec Endoscopic Surgeon and IVF Consultant
M.D.,D.G.O
Director, Dr. Sudha Tandon Fertility, IVF, Endoscopy & Maternity Centre.

Dr. Amrita Tandon
MS, DNB, FMAS, MRM Reproductive Medicine (London)
Gynaec Endoscopic Surgeon and IVF Consultant ,
Dr. Sudha Tandon Fertility, IVF, Endoscopy & Maternity Centre.

Hysteroscopy and Laparoscopy both have a definitive role in the management of infertility and ART . Intrauterine insemination ( IUI ) warrants the presence of a fairly normal reproductive pelvic organ structure and function , especially the patency of the fallopian tubes. The role of endoscopic surgery has been established before IUI in case of known correctable pelvic pathology.  It’s role has been debated in case of unexplained infertility especially when there is failure of IUI due to unknown reasons .

Advances in imaging techniques with 2 dimensional and 3 dimensional ultrasound, saline infusion sonography, computerized tomography (CT), and magnetic resonance imaging (MRI) for the evaluation of uterine and pelvic disease have decreased the use of diagnostic hystero-laparoscopy as a first line investigation in patients with infertility.  Hysterosalpingography (HSG) and hysterosalpingo-contrast-sonography (HyCoSy) are inexpensive, lesser invasive, well-tolerated methods of determining tubal patency, but their accuracy compared to laparoscopy is a matter of debate. A number of studies suggest that diagnostic hystero-laparoscopy may be of additional value over the standard first line investigations,  because it indicates intra-abdominal pathologic abnormalities in 36 – 68 % of cases even after a normal HSG.  It is accepted as the most accurate method for evaluating tubal pathological and other pelvic causes of infertility. 1

A study published in Fertility and Sterility (2003) to evaluate the accuracy of diagnostic laparoscopy after normal hysterosalpingography (HSG) and before intrauterine insemination (IUI) with respect to laparoscopic findings leading to a change of treatment decisions in couples with male subfertility, cervical factor, or unexplained infertility concluded that in about 25% of the couples, it led to an alteration in treatment plan. In 21%, intervention was done at the time of diagnostic laparoscopy in terms of adhesiolysis of periadnexal adhesions and treatment of minimal and mild endometriosis with consequent IUI. This also eventually led to an overall increase in live birth rates. Most studies have shown the benefit of laparoscopic surgery for minimal and mild endometriosis prior to IUI. 2

An Indian study by Jayakrishnan et al 3 in 2010, evaluated the  role of Hysterolaparoscopy in patients who had no detectable pathology based on history, physical examination, and ultrasound and had treatment for three or more cycles in the form of ovulation induction and IUI. They reviewed 127 patients who fulfilled the inclusion criteria.  Of the 127 women, 12.6% (n= 16) had no detectable pathology on laparohysteroscopy. The incidence of endometriosis was 77.2% (n= 98); of which 70.9 % had minimal to mild disease. No cases with Stage IV disease were present. 5.5% of patients had pelvic inflammatory disease (PID) with unilateral and bilateral tubal adhesions and tubal blocks. There were no abnormal findings at hysteroscopy.

Endoscopic surgery is invasive and requires the use of general anaesthesia and hence is not without risk of complications. In the recent era of Assisted Reproductive Technologies (ART), the easy availability and faster results of In Vitro Fertilisation (IVF) have led to the decline in use of laparoscopy due to the added expense and possible complications. But it is important to note that the cost of IVF is high and one attempt usually offers only one chance of successful pregnancy . On the contrary in a young infertile woman < 35 years of age, with treatable pelvic pathology, laparoscopic correction can help improve the chance of natural conception and success rates of IUI.

The timing of endoscopic surgery in the management of infertility  has been a matter of debate. Performing a laparoscopy prior to initiating treatment looks attractive, but the cost of this surgical procedure is high. Mostfertility specialists thus prefer to treat couples with unexplained infertility with a few cycles of ovulation stimulation with IUI before proceeding to laparoscopy.

A prospective randomized reallocation study to investigate the timing of laparoscopy after a normal hysterosalpingography was performed 4.  This study, however, showed no significant difference in the prevalence of abnormalities with clinical consequences at laparoscopy before IUI when compared to laparoscopy after six cycles of IUI. It concluded  that the impact of the detection and the laparoscopic treatment of observed pelvic pathology prior to IUI did not seem to affect IUI outcome. The authors raised doubts about the value of routinely performing a diagnostic and/or therapeutic laparoscopy prior to IUI treatment.

TYPES OF ENDOSCOPIC SURGERY IN INFERTILITY PRIOR TO IUI / AFTER FAILED IUI CYCLES:

A) LAPAROSCOPY:

ENDOMETRIOSIS SURGERY : The most common finding on laparoscopy in patients who are unable to conceive with IUI and apparently normal findings on imaging techniques is minimal to mild endometriosis. The possible reasons for subfertility in endometriosis include dyspareunia and alterations in pelvic anatomy and peritoneal and tubal environments. Other proposed mechanisms include interference with fertilisation, oocyte and embryo development, and implantation.

More severe forms of endometriosis which include endometriosis and deeply infiltrating endometriosis are diagnosed accurately with clinical examination and ultrasound and or MRI. Laparoscopy is the gold standard for more subtle lesions of endometriosis like superficial endometriosis. These superficial lesions can be treated with ablation (electrocautery or laser)  or excision and adhesiolysis to restore the tuba-ovarian anatomy during laparoscopy. For endometriomas, the management has been controversial. Most International guidelines suggest endometriotic cyst excision over drainage of a cyst above the size of 4cm prior to IVF,  but there is risk of reduction in ovarian reserve. Most ART specialists prefer IVF over surgical treatment of endometriomas. There is limited evidence on the treatment of endometriomas prior to IUIand most clinicians would recommend surgery followed by natural conception or IVF in women with endometriomas 5
Surgery for Deep infiltrating endometriosis is recommended only for symptom relief and has not shown to improve pregnancy rates with or without ART.

2. ROLE OF TUBAL SURGERY:

Proximal tubal blockage accounts for 10%–25% of tubal disease . It may be due to obstruction resulting from plugs of mucus and amorphous debris, due to spasm of the uterotubal ostium, or due to occlusion, which is a true anatomic blockage from fibrosis due to salpingitis isthmica nodosa (SIN), pelvic inflammatory disease , or endometriosis. Tubal cannulation to treat proximal tubal block can be done via hysteroscopy with laparoscopic confirmation . This should be attempted only if distal tubal pathology is ruled out. Gentle pressure is needed the to overcome the obstruction by tubal cannulation, and if force is required then a true anatomic occlusion is assumed and the procedure should be aborted 6.

A meta-analysis of studies treating patients with bilateral proximal tubal occlusion showed that the obstruction is relieved in approximately 85% of the tubes with tubal cannulation and that approximately half of the patients conceive 7.

Surgery for Distal Tubal disease : Distal tubal disease includes hydrosalpinx and fimbrial phimsosis. A good prognosis is seen with patients who have no more than limited filmy adnexal adhesions, mildly dilated tubes (<3 cm) with thin and pliable walls, and a lush endosalpinx with preservation of the mucosal folds. Laparoscopic neosalpingostomy and fimbrioplasty are carried out by opening a hydrosalpinx or increasing the opening for fimbrial phimosis, respectively. Pregnancy rates after these procedures depend on the degree of tubal disease and are more favorable with good-prognosis patients. Intrauterine and ectopic pregnancy rates after neosalpingostomy for mild hydrosalpinges range from 58% to 77% and from 2% to 8%, respectively 8. There is no evidence to state that IUI treatment increases the pregnancy rates over expectancy management after tubal surgery.

Tubal surgery is the first-line management option for young women less than 35-years-old with minor tubal pathology. The second option should be IVF if there are other factors affecting fertility, if the patient is >38-years-old, if patient had moderate to severe tubal disease, and if one year or more had passed post-surgery for tubal pathology.9

Laparoscopic Ovarian Drilling (LOD):

The proposed mechanisms by which LOD helps is by destruction of androgen producing stroma, causing reduction in the intraovarian and circulating levels of androgens and LH.

PCOS women who have a high LH value , lean PCOS and non-insulin resistant are known to have a better response to LOD. It is usually done in women who are resistant to clomiphene citrate as an alternative to use of gonadotropins. Use of gonadotropins with IUI is second line treatment in CC – resistant PCOS women. As per Cochrane review 2012, it was found that LOD is as effective as ovulation induction in terms of clinical pregnancy or live birth rates, but risk of multiple pregnancy is lower with LOD 10 . The concerns about  LOD are risk of adhesions and ovarian failure following LOD. The hilar region should be avoided and the ovary should be raised before the application of energy and saline wash should be done after the procedure to lower the risk of injury. The usual dictum is application of 4 diathermy points to each ovary for 4 seconds each , and using a power of 40W. 11

Regarding the efficacy of ovarian drilling, observational studies demonstrated that the ovulation rate was between 54 and 76% in the 6 months after the procedure and 33 and 88% in the 12 months after the procedure. During these periods, the spontaneous pregnancy rate ranged between 28 and 56% and 54 and 70%, respectively. 12

REPRODUCTIVE

HYSTEROSCOPIC SURGERY PRIOR TO IUI:

Hysteroscopy is the most accurate method to diagnose and treat unsuspected and subtle intrauterine pathologies in the infertile women. Uterine pathologies like endometrial polyps, uterine septa, intrauterine adhesions and submucosal fibroids cause infertility by impairing embryo implantation and growth due to poor vascularisation , affecting sperm migration, or by causing an inflammatory endometrial response.

Hysteroscopic Polypectomy :

Perez-Medina et al.13 randomised women with a clear sonographic diagnosis of endometrial polyps and at least 1 year of infertility to hysteroscopy and polypectomy or diagnostic hysteroscopy and polyp biopsy prior to planned intrauterine insemination (IUI) treatment. The mean polyp diameter in the treated group was 16 mm (3–24 mm). The pregnancy rates after four cycles of stimulated IUI starting at least 3 months after surgery were significantly higher in the polypectomy group (63% versus 28%).

Similarly in another study by Kalampokas et al 14 study group consisted of 86 women who, following the diagnosis of endometrial polyp, underwent hysteroscopic polypectomy and the control group consisted of 85 women who chose not to undergo polypectomy before IUI. There was a statistically significant difference in cumulative pregnancy rates between the two groups. The group that underwent polyp removal had higher pregnancy rates as compared to the one that the polyps were left intact following IUI.  Hence , hysteroscopic removal of polyps has shown to improve the pregnancy rates after IUI .

Intrauterine adhesions :

A more recent study by Chen et al 15 evaluated the reproductive outcomes in 357 patients with mild, moderate, and severe Asherman’s syndrome who underwent hysteroscopic adhesiolysis. The reproductive outcomes of 332 women (93%) were followed for an average duration of 27±9 months, and the overall conception rate after hysteroscopic adhesiolysis was 48.2%, which decreased with increased intrauterine adhesions (IUA) severity (mild, 60.7%; moderate, 53.4%; severe, 25%). The mean time to conception following hysteroscopic adhesiolysis was 9.7±3.7 months. The miscarriage rate was 9.4%, and the live birth rate was no lower than 85.6%. Eleven patients (7.9%) had postpartum hemorrhage, including 6 (4.3%) due to adherent placenta and 3 (2.1%) due to placenta accreta.Hysteroscopic adhesiolysis is a feasible and effective way to improve fertility in patients with Asherman’s syndrome.

Hysteroscopic division of adhesions with scissors or electrosurgery is usually recommended. Some women may require multiple procedures to achieve a satisfactory anatomical result due to the high recurrence rate. Second Look hysteroscopy with re-adhesiolysis is usually recommended. Postoperative mechanical distension of the uterine cavity with an intrauterine device or a paediatric foley’s catheter along with oestrogen therapy to facilitate endometrial regrowth and proliferation are commonly used to decrease the high rate of recurrence.

OTHER ENDOSCOPIC SURGERIES:

The other fertility enhancing endoscopic surgeries like hysteroscopic myomectomy for submucosal fibroids, hysteroscopic septal resection, laparoscopic myomectomy are known to improve fertility outcomes and hence indirectly also improve success rates of IUI.

To conclude, endoscopic surgeries have a role in optimising the outcome of IUI , provided, done for the correct indication, and with standard techniques as suggested by research.

Couples who fail to conceive with ovulation stimulation with IUI should be counselled that there is evidence to show that laparoscopy is of benefit before proceeding to IVF . At the same time, the use of empirical treatment in the form of ovulation stimulation and IUI prior to laparoscopy might reduce the number of patients requiring the procedure, reduce the number of negative laparoscopies, and optimize resource utilization.

REFERENCES:

  1. Yalanadu N Suresh, Nitish N Narvekar, The role of tubal patency tests and tubal surgery in the era of assisted reproductive techniques, The Obstetrician & Gynaecologist, 10.1111/tog.12070, 16, 1, (37-45), (2014).
  2. Tanahatoe S, Hompes PG, Lambalk CB. Accuracy of diagnostic laparoscopy in the infertility work-up before intrauterine insemination. Fertil Steril. 2003;79(2):361-366. doi:10.1016/s0015-0282(02)04686-1
  3. Jayakrishnan K, Koshy AK, Raju R. Role of laparohysteroscopy in women with normal pelvic imaging and failed ovulation stimulation with intrauterine insemination. J Hum Reprod Sci. 2010;3(1):20-24. doi:10.4103/0974-1208.63117
  4.  Tanahatoe SJ, Lambalk CB, Hompes PG. The role of laparoscopy in intrauterine insemination: A prospective randomized reallocation study. Hum Reprod 2005;20:3225-30.
  5. Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database Syst Rev 2008;(2):CD004992.
  6. Role of tubal surgery in the era of assisted reproductive technology: a committee opinion, Fertility and Sterility, Volume 103, Issue 6, e37 – e43
  7. Honore GM, Holden AE, Schenken RS. Pathophysiology and management of proximal tubal blockage. Fertil Steril 1999;5:785–95.
  8. Nackley AC, Muasher SJ. The significance of hydrosalpinx in in vitro fertilization. Fertil Steril 1998;69:373–84.
  9. Daniilidis A, Balaouras D, Chitzios D, Theodoridis T, As- simakopoulos E. Hydrosalpinx: Tubal surgery or in vitro fertilisation? An everlasting dilemma nowadays; a narra- tive review. J Obstet Gynaecol. 2017; 37(5): 550-556. doi: 10.1080/01443615.2017.1287685
  10. Farquhar C, Brown J, Marjoribanks J. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2012;(6):CD001122. Published 2012 Jun 13. doi:10.1002/14651858.CD001122.pub4
  11. Armar NA, McGarrigle HH, Honour J, Holownia P, Jacobs HS, Lachelin GC. Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: endocrine changes and clinical outcome. Fertil Steril. 1990;53(1):45-49.
  12. Unlu C, Atabekoglu CS. Surgical treatment in polycystic ovary syndrome. Curr Opin Obstet Gynecol. 2006;18(3):286–92. doi: 10.1097/01.gco.0000193020.82814.9d.
  13. Perez-Medina T, Bajo-Arenas J, Salazar F, Redondo T, Sanfrutos L, Alvarez P, et al. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod 2005;20:1632–5.
  14. Kalampokas T, Tzanakaki D, Konidaris S, Iavazzo C, Kalampokas E, Gregoriou O. Endometrial polyps and their relationship in the pregnancy rates of patients undergoing intrauterine insemination. Clin Exp Obstet Gynecol. 2012;39(3):299-302.
  15. Chen L, Zhang H, Wang Q, et al. Reproductive Outcomes in Patients With Intrauterine Adhesions Following Hysteroscopic- Adhesiolysis: Experience From the Largest Women’s Hospital in China. J Minim Invasive Gynecol. 2017; 24(2): 299-304.