|Ahead of print publication
Reproductive outcomes and predictors for success following hysteroscopic tubal cannulation for proximal tubal disease
Samuel Dobson1, Elizabeth Halley2, Jonathan D Skull1, Mostafa Metwally1, Bolarinde Ola1
1 Department of Obstetrics and Gynaecology, Assisted Conception Unit, Jessop Wing, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
2 Department of Obstetrics and Gynaecology, Jessop Wing, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
|Date of Submission||03-Jul-2020|
|Date of Acceptance||15-Jan-2021|
|Date of Web Publication||23-Jul-2021|
Department of Obstetrics and Gynaecology, Assisted Conception Unit, Jessop Wing, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield
Source of Support: None, Conflict of Interest: None
Context: Tubal factor sub-fertility accounts for approximately 12% of IVF treatment cycles performed in the UK. Current data suggests that following hysteroscopic tubal cannulation, patients can expect a comparable LBR of 22% and spontaneous CPR of 25-27%, versus a LBR of 21% and CPR of 36.3% per cycle of IV. Our study is a l retrospective study, looking at reproductive outcomes after hysteroscopic cannulation of proximal tubal disease. Aims: investigate the effectiveness of hysteroscopic tubal cannulation (HTC) for the treatment of patients with proximal tubal obstruction (PTO). Settings and Design: Retrospective study. Methods: All patients underwent HTC for either unilateral (n= 53) or bilateral PTO (n= 33) between 2009 and 2018. Fertility outcomes were collected over following 24 months. Results: Overall CPR and live birth rate (LBR) following successful HTC was 26.9% and 22.2% respectively. Patients aged 20-35 years achieved a significantly higher CPR (38.5% vs 8.33%; Odds ratio (OR) 6.875; 95% confidence interval (CI) 1.41-33.54) and LBR (30.8% vs 8.3% OR 5.5; 95% CI 1.118-27.1) compared to 36-45 year-olds.
Keywords: Chromopertubation, hysteroscopy, proximal tubal obstruction, tubal cannulation, tubal infertility
|How to cite this URL:|
Dobson S, Halley E, Skull JD, Metwally M, Ola B. Reproductive outcomes and predictors for success following hysteroscopic tubal cannulation for proximal tubal disease. Afr J Infertil Assist Concept [Epub ahead of print] [cited 2021 Nov 28]. Available from: https://www.afrijiac.org/preprintarticle.asp?id=322194
| Introduction|| |
Approximately one in seven couples (14%) will experience difficulty conceiving, with tubal disease accounting for approximately 10%–15% of infertility. The causes of tubal disease include pelvic inflammatory disease, endometriosis, polyps, and previous surgical trauma., Proximal tubal obstruction (PTO) may also be due to spasm, mucus plugs, uterine curettage, and abortion. Data collected in the UK show that there were 68,000 in vitro fertilization (IVF) treatment cycles performed in 2016, of which an estimated 12% were due to tubal disease. Due to advances in assisted reproductive techniques, tubal cannulation is now less commonly performed.
With the advent of IVF, couples can now expect an overall live birth rate (LBR) of 21% and a clinical pregnancy rate (CPR) of 36.3% per cycle. For those under 35 years of age, LBR is 26%–29% per IVF cycle. In light of changes to funding within the NHS over the last decade, only 12% of clinical commissioning groups now fund three cycles of IVF, compared with 24% in 2013. As such, other treatment options with equivalent success rates are increasingly needed.
NICE recommendation is that, for women with PTO, hysteroscopic tubal cannulation (HTC) is a suitable treatment, aimed at increasing the chance of spontaneous conception without a requirement for IVF. While based on mixed quality data, two recent studies including a systematic review and meta-analysis have shown a comparable pooled LBR of 22% and spontaneous CPR of 25%–27% following HTC., It must also be remembered that successful tubal cannulation not only avoids the high costs of IVF but also can allow patients to conceive multiple times unaided. Tubal cannulation is relatively inexpensive, minimally invasive, and can be performed at the same time as laparoscopic chromopertuberation, with a tubal patency success rate of around 80%–90%.,,
All studies identified in the recent meta-analysis were retrospective with only three studies published within the past 7 years,,, one of which included only 27 patients. The same meta-analysis contained a significant degree of clinical heterogeneity with multiple studies using patients undergoing concurrent ovulation induction or treatment for other factors. These studies also lack subgroup analyses, meaning clinicians still lack important information needed to help select patients that would benefit the most from HTC and thus identify those who would be better served by quicker recourse to IVF.
In light of the gaps in the current evidence available, this study aims to review the safety and long-term reproductive outcomes following HTC for PTO, as well as identify predictive factors to help clinicians counsel their patients.
| Subjects and Methods|| |
In this retrospective case series, we included all patients who underwent HTC for proximal tubal occlusion (PTO) over a 9-year period between 2009 and 2018 at the Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Trust, UK (n = 87). The study was approved by the institutional review board, and the process of data collection was consistent with data protection regulations. Patients were separated based on age, into two subgroups, 20–35 years and 36–45 years. Prior to surgery, all patients had undergone routine fertility investigations to confirm ovulation (day 21 serum progesterone >30 nmol/L), normal semen analysis, normal ultrasound imaging of the female reproductive organs, and tubal assessment, confirming either unilateral or bilateral tubal blockage. Tubal assessment was either by hysterosalpingogram (HSG) or laparoscopic chromopertuberation. Laparoscopic chromopertuberation was performed first line when there was suspicion of coexisting pelvic pathology (e.g., previous history of chlamydia or dysmenorrhea suggesting endometriosis). Three patients were noted to have received clomiphene postoperatively. No patients included in this study were documented to have concomitant distal tubal disease, significant endometriosis, or pelvic disease during their laparoscopy.
All patients with suspected tubal blockage on HSG were offered laparoscopic chromopertubation (dye test) under general anesthetic. Dilute methylene blue dye was used to determine whether a unilateral or bilateral PTO was present, prior to HTC at the same operation. Most surgeons performed routine laparoscopy and dye test; one surgeon preferred hysteroscopic selective chromopertubation with the outer catheter of the Novy cannulation set passed through the operating channel of a 15°–30° hysteroscope. Tubal blockage was determined by a lack of observable distension of the tube with dye. Tubocornual cannulation was then attempted on the obstructed tube or tubes, using a fine Novy cornual catheter (Modified Novy Cornual Cannulation set, Cook UK©) which was introduced into the proximal tubal ostium. The flexible guidewire within the inner catheter was removed and dye test performed with a 5 ml syringe. Seldom, if the tube was still blocked, the guidewire was gently advanced through the outer catheter by 1–2 cm into the proximal Fallopian tube More Details, under laparoscopic vision. The guidewire was again removed, and a further methylene dye was then injected through the inner catheter to demonstrate whether tubal patency had been achieved. Successful cannulation was confirmed by observing the filling and spilling of dye into the abdominal cavity, on laparoscopy, from the fimbrial end of the cannulated tube(s). Cannulation was not performed on patients with clear bipolar or distal tubal blockage(s).
Data were collected from hospital electronic result databases, operation notes, and patient notes. Data included patient demographics, results of HSG (if applicable), operative findings before and after HTC, postoperative recovery/complications, and reproductive outcomes (CPR/LBR/miscarriage/ectopic pregnancy). Reproductive outcomes were collected from review of electronic hospital records of blood tests and ultrasound scans from a large geographical area of seven hospitals (Chesterfield, Worksop, Barnsley, Doncaster, Rotherham, the Sheffield Northern General Hospital, and Hallamshire hospital). The minimum follow-up period was 24 months following HTC. All patients who conceived during follow-up were followed until delivery.
Data collected were then inputted on to a spreadsheet database and analyzed using SPSS version 25 for windows (Statistical Package for the Social Sciences, IBM, Chicago, IL, USA). Student's t-test and Chi-squared test were used for assessing continuous and categorical data, respectively. A P < 0.05 was considered to be statistically significant.
The primary outcome was live birth following successful HTC. Secondary outcomes included clinical pregnancies (confirmed by either a positive serum Beta HCG or fetal heart on a first trimester ultrasound), success rate of HTC, ectopic pregnancy, miscarriage, and any adverse outcomes. Demographic information collected included age, pretreatment day 2–6 serum follicle-stimulating hormone (FSH) levels (IU/ml), and body mass index (BMI).
| Results|| |
The mean age (standard deviation [SD]) was 34 years (±5.7) for the overall population. The mean age (SD) for the age group of 20–35 years (n = 54) was 30.4 years (±3.5) and for 36–45 years (n = 32) was 40 years (±2.6), respectively. Comparison of FSH (IU/L) levels (SD) showed no significant difference between the two patient subgroups (6.5 [2.1] vs. 7.6 [3.5], P ≥ 0.05); however, BMI (SD) did demonstrate a significant difference between the subgroups (26.2 [5.2] vs. 28.5 [5.2], P = 0.045).
[Table 1] represents the spontaneous CPR, LBR, average duration before conception, and miscarriage rate overall and for each subgroup following successful HTC. Overall, the spontaneous CPR and LBR were 17/63 (26.9%) and 14/63 (22.2%), respectively. Patients aged 20–35 years were statistically more likely to conceive spontaneously following tubal cannulation compared with patients aged 36–45 years (15/39 [38.5%] vs. 2/24 [8.33%]; odds ratio [OR] 6.875, 95% confidence interval [CI] 1.41–33.54; P = 0.009). The same was seen for LBR (12/39 [30.8%] vs. 2/24 [8.33%]; OR: 5.5, 95% CI: 1.12–27.1; P = 0.024). The two pregnancies and live births seen in the 36–45 years cohort were aged 37 and 39 years and both had live births. The time to conception (months [SD]) was not significantly different between the two subgroups (8.75 [±12.8] vs. 10 [±4.2], P = 0.9). The miscarriage rate overall was 17.6% (3/17), with all miscarriages occurring in the 20–35-year age group.
|Table 1: Outcomes by age group (clinical pregnancy rate/live birth rate)|
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Pretreatment FSH levels (SD) were significantly lower in patients who achieved a clinical pregnancy following successful HTC (5.6 [1.64] vs. 7.3 [2.8], P = 0.021). The same was seen for age (SD) (30.8 [4.76] vs. 35.2 [5.42], P = 0.004). However, there was no significant difference in BMI (SD) between patients who did and did not achieve a clinical pregnancy (26.8 [6.18] vs. 27.3 [4.96], P = 0.792).
[Table 2] demonstrates that bilateral PTO was noted in 33/86 (38.4%) patients and unilateral PTO in 53/86 (61.6%) patients undergoing laparoscopic chromopertuberation. Those with unilateral PTO were significantly more likely to have a left-sided PTO compared to a right-sided PTO on laparoscopy (36/53 [67.9%] vs. 17/53 [32.1%]; 95% CI: 0.18–0.54; P = 0.0002). Tubal cannulation was successful in 43/53 (81.1%) patients with unilateral PTO and in 20/33 (60.6%) patients with bilateral PTO. However, 5/33 (15.2%) patients with bilateral PTO had successful cannulation of only one tube. Patients with unilateral PTO were significantly more likely to achieve tubal patency following HTC (P = 0.037). Overall, 73.3% (63/86) had successful HTC of at least one tube at surgery. Following successful tubal cannulation, the CPR for unilateral HTC, bilateral HTC, and overall was 32.5% (14/43), 15% (3/20), and 26.9% (17/63), respectively, with no significant difference between unilateral and bilateral PTO (OR: 2.736; 95% CI: 0.686–1.09). LBR for patients who underwent unilateral HTC, bilateral HTC, and overall was 27.9% (12/43), 10% (2/20), and 22.2% (14/63), respectively, and again there was no significant difference between the groups (OR: 2.194; 95% CI: 0.543–8.865).
|Table 2: Site of tubal obstruction, spontaneous pregnancy rate, and live birth rate|
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Of those who conceived following successful HTC, 12/17 (70.5%) patients had achieved a clinical pregnancy by 6 months, 13/17 (76.5%) by 9 months, and 14/17 (82.3%) by 12 months. Cumulative CPR [Time to conceive - Graph 1] was 18.9% at 6 months, 20.6% at 9 months, and 22.14% at 12 months. All recorded spontaneous pregnancies had occurred by 24 months.
Following the tubal cannulation and successful live birth, 3/14 (21.4%) patients went on to have further additional clinical pregnancy after live birth within the short follow-up period. From our review of the case notes, we identified one ectopic pregnancy (1/17 [5.8%]) who underwent a salpingectomy and had further spontaneous pregnancy and live birth 2 years later. There was one reported allergic reaction to penicillin intraoperatively.
| Discussion|| |
The data from this study support recent publications, demonstrating that following successful HTC more than a quarter of couples will achieve a clinical pregnancy and more than one-fifth are live births within 12 months., The high success rate in achieving tubal patency following HTC in this study, while not as high as another recent small prospective study, is similar to other previous studies.,, This study also supports the use of HTC as an option for women with proximal tubal factor infertility. While our overall CPR of 26.9% following successful HTC is lower than that quoted for IVF of 36.3%, in women under 36 years old, we have identified an equivalent CPR compared to IVF.
This is one of the largest studies within the past 10 years to review reproductive outcomes following HTC and the first to identify predictive factors and subgroups of patients who may benefit most from HTC. While this study was retrospective in nature, care was taken to collect all the necessary information from hospital databases which covered a wide geographical area, minimizing the chance of missing important outcome data. By limiting our follow-up period to 24 months, we accept that the true natural CPR rate may be higher than that quoted. While we found no documented cases of significant adhesions, endometriosis, or concurrent male factor infertility, three patients were treated with empirical clomiphene citrate post HTC, introducing some degrees of clinical heterogeneity to the group.
This study separates patients by age group and pregnancy outcomes in order to identify predictors of success so that clinicians can use when counseling patients about their options. As may be expected, we found that CPR and LBR were significantly higher for those in the younger age group, with no pregnancies occurring in anyone over 39 years. We also showed a significant difference in the average age of those that did conceive, further supporting age as a significant predictor of success. Compared to IVF in the older age group, in which LBR figures are quoted as 14%, our LBR was nearly half of this. This suggests that the older age group would be best served by moving to IVF earlier, especially if funding is available. In the younger age group, our CPR and LBR were equal to IVF, supporting HTC as a viable alternative. This would avoid costly IVF cycles and allow the possibility for further future pregnancies, which within our limited follow-ups were seen in this study.
Day 2 FSH levels in patients who did not achieve a clinical pregnancy were significantly higher than in those who did achieve a clinical pregnancy; however, the trend for higher FSH levels in women 36–45 was nonsignificant. We cannot comment on a particular cutoff value for FSH at which HTC should be avoided. However, it may be sensible for clinicians to counsel those patients with raised FSH levels and thus evidence of follicular depletion, about the benefits of early recourse of IVF.
This study demonstrated that patients with unilateral tubal disease were significantly more likely to have successful HTC. However, it only demonstrated a nonsignificant trend for a higher CPR and LBR in patients with unilateral tubal obstruction compared with bilateral tubal obstruction, likely due to the small group size and low powers. The above findings may support the concept that patients with bilateral PTO have more severe tubal disease, impacting their overall chance of conception and successful HTC. While this may be another useful prognostic indicator, a recent meta-analysis also demonstrated no significant difference in pregnancy outcomes in patients with unilateral and bilateral PTO and as such its use in predicting success is uncertain.
Our study supports allowing patients to try for a natural conception for 6 months following HTC. At this point, cumulative pregnancy rates plateau and around 70% of patients who would achieve a pregnancy will have done so. These findings support previous studies. However, when deciding when to move on to assisted reproductive treatments, the clinician must take into account all other factors such as patient wishes, age, and funding.
Our miscarriage rate of 17.6% is in keeping with the expected miscarriage rate for women of this age. We found one ectopic pregnancy following HTC giving an incidence of 5.8%; this is comparable to the 4% incidence previously reported but higher than the background risk of ectopic of around 1%., We would support the theory that these women do have a higher risk of ectopic pregnancy, likely due to underlying tubal disease and as such should be counseled with regard to this risk prior to surgery.
| Conclusion|| |
In conclusion, HTC for PTO appears to be an effective alternative to immediate recourse to IVF in younger women. In those who are under 36 years of age, with unilateral tubal disease and normal basal FSH levels, CPR and LBR appears comparable to outcomes from one cycle of IVF. Further prospective studies are required to confirm our findings.
This study was supported by Sheffield Teaching Hospitals Clinical Effectiveness Unit(CEU), Registered March 2019, Registration number 9149.
This was a report of a series by multiple operators in teams, at various times: Professor TC Li FRCOG, Professor W Ledger FRCOG, Dr. H. Lashen FRCOG, Mr. JD Skull MRCOG, Mr. B. Ola FRCOG, Miss V. Tamhankar MRCOG, and Mr. M Metwally FRCOG; all of who were consultant gynecologist and (sub-) specialists in reproductive medicine and surgery at the Sheffield Teaching Hospital NHS Foundation Trust.
Financial support and sponsorship
This study was supported by Sheffield Teaching Hospitals Clinical Effectiveness Unit(CEU), Registered March 2019, Registration number 9149.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]