Endometrial cancer in a woman undergoing hysteroscopy for recurrent IVF failure

Background

Hysteroscopy, despite being the undisputed gold standard for the examination of the uterine cavity, is controversial as a routine procedure in infertile women. However, benign intrauterine conditions are common in women suffering repeated in vitro fertilization (IVF) failure, and growing evidence suggests a unique diagnostic and therapeutic role for hysteroscopy. Endometrial malignancy, on the contrary, is unreported by large published series of women with repeated IVF failures undergoing hysteroscopy, and its impact on fertility, for obvious reasons, has not been studied.

Results

An unsuspected endometrial cancer was diagnosed in an asymptomatic 38-year-old woman undergoing hysteroscopy because of several repeated failures of in vitro fertilization and embryo transfer.

Conclusions

Endometrial cancer can be found at hysteroscopy in young women with repeated IVF failures. The possibility of repeatedly unsuccessful fertility treatments should be taken into account when counseling infertile women about conservative treatment of endometrial cancer.

Background

During the last decades, developments in ultrasound diagnostics and increased knowledge about the determinants of assisted reproduction’s success have caused a downgrading of gynecological endoscopy’s role in the assessment of female infertility. Hysteroscopy, for instance, in spite of being the undisputed gold standard for the examination of the uterine cavity, is controversial as a routine procedure [1]. However, growing evidence suggests a unique diagnostic and therapeutic role for hysteroscopy, especially in cases of repeated failures of assisted reproductive technology [2]. In such cases, abnormal hysteroscopic findings, such as endometrial polyps, submucous fibroids, adhesions, and septa, are common [3,4,5], and hysteroscopy offers an opportunity for diagnosis and a convenient see-and-treat management [2, 6]. Endometrial malignancy, on the contrary, is unreported in large published series [3,4,5], and its impact on fertility, for obvious reasons, has not been studied.

We here present and discuss a case of unsuspected endometrial cancer which was accidentally diagnosed in a woman undergoing hysteroscopy because of repeated failure of in vitro fertilization (IVF) and embryo transfer (ET).

Methods

The data of this case report was obtained through retrospective chart review.

Results

A 38-year-old woman and her male partner had been under our care for primary infertility, at the Centre for Reproduction of Uppsala University Hospital, for 3 years. She had a normal body mass index (BMI; 22 kg/m2) and regular ovulatory menstrual cycles. Previously, she had used combined oral contraceptives followed by an intrauterine device for 10 years. Baseline infertility investigations, including hormonal assessments for TSH and prolactin, pelvic ultrasonography, and semen analysis, were unremarkable. Tubal perviousness and no abnormalities were seen at hysterosalpingo-contrast sonography.

After the diagnosis of unexplained infertility, she had undergone three ovarian stimulations, one with clomiphene citrate, and the following two with low-dose follicle-stimulating hormone (FSH) followed by intrauterine insemination. No pregnancy had been obtained. The couple had then undergone two IVF treatments after conventional controlled ovarian stimulation, each one leading to one fresh elective single embryo transfer (SET) and to several frozen single or double embryo transfers (DET). Overall, eight embryo transfers (two fresh SET, four frozen SET, and two frozen DET) had been performed, but no intrauterine clinical pregnancy was ever achieved. A biochemical pregnancy occurred after the third transfer of the series (frozen). The fifth ET (frozen) resulted in a tubal pregnancy, which was managed by laparoscopic salpingectomy.

Prior to the start of a new controlled ovarian stimulation for IVF-ET, it was agreed to perform a hysteroscopy to rule out intrauterine abnormalities, in view of the several previous failures. At hysteroscopy, a small polypoid growth, having its base at the fundal region, was seen. Pathology of the resected specimen returned a diagnosis of endometrial atypia. After counseling, a conservative treatment with oral progestins (medroxyprogesterone acetate 10 mg daily) was commenced. However, an outpatient endometrial biopsy by pipelle at a 3-month follow-up showed endometrial cancer of endometrioid type. The patient was thoroughly counseled by fertility and oncology specialists about the possible therapeutic strategies, ranging from conservative treatments with progestins to the standard surgical staging for endometrial cancer. As a result of her informed choice to undergo surgery, a total hysterectomy with bilateral salpingectomy and preservation of the ovaries was performed by the gynecologic oncology surgeons. Surgery and the postoperative period were uneventful. The final pathology report described a highly differentiated, diploid, endometrioid adenocarcinoma of the endometrium which was classified as FIGO stage IA (G1). No adjuvant treatment was needed. At all planned follow-up visits, in accordance with local guidelines, she was always disease-free and reported a 100% score on quality-of-life measures. At our last contact, 5 years after the hysterectomy, she also reported having adopted a child and enjoying her motherhood.

Discussion

Hysteroscopy is not universally considered a routine procedure for the evaluation of the uterine cavity in subfertile women [1]. However, there is a high prevalence of previously undetected intrauterine abnormalities in IVF patients, particularly following to failed treatments [3,4,5]. This gives a pragmatic measurement of the diagnostic potential of hysteroscopy, if we consider that women with failed treatments constitute a selected population which has obviously undergone several prior ultrasound exams. Besides, growing evidence, albeit of limited quality, suggests that hysteroscopic diagnosis and, when needed, treatment may improve IVF outcomes and also be cost-effective [2, 7].

Benign hysteroscopic findings are common among IVF patients, the majority of which being represented by endometrial polyps, submucous fibroids, adhesions, or uterine anomalies [3,4,5]. On the contrary, an endometrial malignancy is not an expected finding in these women. Endometrial cancer, in spite of an approximate lifetime risk of 2.8% women, is a rare occurrence before 40 years old [8, 9].

Our patient was 38 years old, and no intrauterine abnormality was ever diagnosed or suspected during 3 years of repeated fertility treatments. Hysteroscopy was only performed in view of the several failures and revealed a small polypoid growth that had not been seen at ultrasound. Polyps are an increasingly common finding [3, 10]; however, their association with malignancy is controversial in younger and asymptomatic women [11]. In our case, in spite of hysteroscopic resection and oral progestins treatment, the initially diagnosed atypia turned out to be an endometrial cancer at final diagnosis, which is a known possibility [12]. The cancer was also still present on the final specimen, meaning that it was not confined to the resected polypoid area, as often reported in the literature [12]. It seems therefore worth reminding that, although conservative treatment of early stage endometrial cancer by means of progestins and hysteroscopic resection has been proposed [9, 13], the gold standard includes a total hysterectomy [14]. In this case, following a patient-centered approach to care, the choice of undergoing hysterectomy was made by the patient after thorough information about different therapeutic alternatives. In spite of that, she could still fulfill her desire for motherhood through adoption.

Whether a link existed, in this case, between infertility and the malignancy is an intriguing albeit difficult question. Infertility does not seem to represent a strong risk factor for endometrial cancer, although some conditions such as chronic anovulation in PCOS patients imply unopposed estrogenic effect on the endometrium, hence a risk for abnormal proliferation [15]. Our patient had ovulatory cycles but had undergone various ovarian stimulations with gonadotrophins as well as hormonal replacement treatments for frozen embryo transfer. Her endometrial cancer was of endometrioid type, which is closely related to estrogens. Some studies have previously shown an increased risk for endometrial cancer in women receiving gonadotrophins and clomiphene for fertility treatment although a real causal relationship is far from demonstrated [16].

One could also wonder whether the neoplasia might have played a role in the several failed treatments experienced by our patient. While benign intrauterine conditions are thought to interfere with endometrial receptivity, the hypothesis of an association of endometrial cancer with implantation failure is suggestive but unverified. This possibility should however be kept in mind when counseling subfertile patients about conservative treatments of endometrial cancer, since much of the knowledge on fertility outcomes is based on experiences with fertile women.

Conclusions

Malignancy, albeit rare, is a possible occurrence in younger women undergoing fertility treatments. In the present case, an early diagnosis of endometrial cancer was facilitated by hysteroscopy, which was performed because of repeated IVF failures in a woman with no specific symptoms nor ultrasonographic signs of pathology. The possibility of repeatedly unsuccessful fertility treatments should be taken into account when counseling infertile women about conservative treatment of endometrial cancer.

Source -  https://gynecolsurg.springeropen.com/articles/10.1186/s10397-017-1009-1

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To More Post: Treating suspected uterine cavity abnormalities by hysteroscopy to improve reproductive outcome in women with unexplained infertility or prior to IUI, IVF, or ICSI

Treating suspected uterine cavity abnormalities by hysteroscopy to improve reproductive outcome in women with unexplained infertility or prior to IUI, IVF, or ICSI

Abstract - Endometrial polyps, submucous fibroids, uterine septa, and intrauterine adhesions can be found by ultrasound (US), HSG, hysteroscopy, or any combined in 10–15 % of infertile women. Observational studies suggest a better reproductive outcome when these anomalies are removed by operative hysteroscopy. The current Cochrane review assesses the effectiveness of hysteroscopy for treating these suspected anomalies in women with otherwise unexplained infertility or prior to intrauterine insemination, in vitro fertilization, or intracytoplasmic sperm injection.

Background - Endometrial polyps, submucous fibroids, uterine septa, and intrauterine adhesions can be found by ultrasound (US), HSG, hysteroscopy, or any combined in 10–15 % of infertile women. Observational studies suggest a better reproductive outcome, when these anomalies are removed by operative hysteroscopy. The current Cochrane review assesses the effectiveness of hysteroscopy for treating these suspected anomalies in women with otherwise unexplained infertility or prior to intrauterine insemination (IUI), in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI) [1].

Methods - We searched electronic databases including CENTRAL (The Cochrane Library 2012, Issue 7), MEDLINE (1950 to 27 October 2012), and EMBASE (1974 to 27 October 2012) conference proceedings from the American Society for Reproductive Medicine through hand searching (from 2008 to 30 October 2012) and reference lists of retrieved articles. Eligible reports were parallel-design randomized trials (RCTs), comparing operative hysteroscopy with a control intervention in women with suspected uterine cavity abnormalities and otherwise unexplained infertility or undergoing IUI, IVF, or ICSI. The primary outcomes were live birth and hysteroscopy complication rates. Secondary outcomes were ongoing or clinical pregnancy and miscarriage rates. We expressed the dichotomous outcome measures as Mantel–Haenszel odds ratios (ORs) with 95 % confidence intervals (CIs) using a fixed-effect model.

Results - Only two studies met the eligibility criteria for inclusion in the review. One study included 94 women with otherwise unexplained infertility and not more than two submucous fibroids or one submucous fibroid combined with one intramural fibroid, all smaller than 40 mm [2]. The second trial [5] assessed the effectiveness of the hysteroscopic removal of endometrial polyps with a mean diameter of 16 mm diagnosed by Doppler US in 215 women bound to undergo gonadotropin treatment and IUI for unexplained, male or female factor infertility for at least 2 years. Both trials used computer-generated random number tables; in only one allocation concealment was adequate [5]. Blinding of patients, personnel, and outcome assessors was not assessed because these items are less relevant in the setting of a surgical trial with unequivocal outcomes and a long follow-up period. Both studies were at low risk for attrition bias but had some potential for selective outcome reporting; no data for live birth rates were available despite long follow up periods of 86 [2] and 50 months [5]. We could not do a formal assessment of publication bias, since only two RCTs were included in the current review.

Primary outcomes: live birth and hysteroscopy complication rates

We retrieved no data for all primary outcomes.

Secondary outcomes

Clinical pregnancy rates

Removal of not more than two submucous fibroids or one submucous fibroid combined with one intramural fibroid, all smaller than 40 mm, in women with unexplained infertility for at least 1 year tends to increase the odds of clinical pregnancy compared to regular fertility-oriented intercourse. The differences between both comparison groups fail to reach statistical significance (OR 2.4, 95 % CI 0.97–6.2) (Fig. 1). Our results are not in accordance with the calculation of the authors in the primary study report; they reported statistically significant differences between both comparison groups both in women with not more than two submucous fibroids only or one submucous combined with one intramural fibroid [2].

The hysteroscopic removal of endometrial polyps with a mean size of 16 mm increases the odds of clinical pregnancy prior to IUI for unexplained male or female factor infertility for at least 2 years, compared to diagnostic hysteroscopy and polyp biopsy only (OR 4.4, 95 % CI 2.5–8.0).

Miscarriage rates

There is no evidence for differences in the miscarriage rates after the hysteroscopic removal of not more than two submucous fibroids or one submucous fibroid with one intramural fibroid in women with otherwise unexplained infertility for at least 1 year, compared to regular fertility-oriented intercourse (OR 1.5, 95 % CI 0.47–5.00).

Conclusions - The only randomized study published in the literature on the hysteroscopic removal of fibroids in infertile women has claimed statistically significant differences in the clinical pregnancy rates between both comparison groups. Our own recalculation of the available data fails to demonstrate statistically significant differences. This statistical error raises concerns about the validity of the published primary data. Moreover, we judged the overall study quality study to be very low. This has implications for clinical research; additional RCTs studying the effectiveness of hysteroscopic myomectomy in infertile women are needed. The implications for daily practice are more controversial. The gynecological profession widely accepts that submucosal and intramural fibroids interfere with fertility in decreasing order of importance based on the results and conclusions of a large systematic literature review with a meta-analysis of observational studies [6, 7]. While conservative, medical, and surgical treatment are all considered as being appropriate for treating symptomatic fibroids, myomectomy seems the only reasonable treatment option for women who wish to become pregnant. Women treated by hysteroscopic myomectomy for submucosal fibroids might have similar reproductive outcomes as infertile women with normal uterine cavities [8]. According to one prospective study, the surgical removal of large intramural fibroids in women with otherwise unexplained infertility prior to IVF treatment might increase the likelihood of a successful reproductive outcome [4]. Our critical appraisal of the current evidence supports the conclusion published by others in the recent past; at the present, there is still evidence of uncertainty on the effectiveness of removing fibroids in infertile women [3].

The hysteroscopic removal of endometrial polyps in women bound to undergo IUI for unexplained, male, or female factor infertility for at least 24 months increases the odds of clinical pregnancy compared to diagnostic hysteroscopy and biopsy only. The level of evidence of this single study was graded as high.

More well-designed pragmatic RCTs are needed to assess the effectiveness of the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septa, or intrauterine adhesions in women with otherwise unexplained infertility or prior to IUI, ICSI, or IVF, preferably measuring live birth and adverse events as primary outcomes. The effects of the number, size, and location of the intrauterine pathology as well as the relationship between the timing of the hysteroscopy and subsequent fertility treatment should be addressed by predefined and sensible subgroup analyses.

source - https://gynecolsurg.springeropen.com/articles/10.1007/s10397-013-0798-0

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To More Post: Indications to tubal reconstructive surgery in the era of IVF

Indications to tubal reconstructive surgery in the era of IVF

Abstract - In recent years, the treatment of tubal infertility has witnessed a shift from reconstructive surgery to in vitro fertilization. However, tubal surgery retains specific advantages, and appropriate preoperative evaluation allows improved selection of patients who are candidates for tubal reconstructive surgery by identifying the patients with good reproductive prognosis. Of pivotal importance in the selection of patients is the intratubal direct evaluation performed at salpingoscopy. Term pregnancy rates of approximately 70% and 65% may be obtained in patients with periadnexal adhesions and bilateral distal tubal occlusion, respectively, when a normal tubal mucosa is observed at salpingoscopy.

Introduction

Tubal factor infertility accounts for approximately 25–35% of cases of female infertility [1–3].

Identifiable causes of tubal infertility are postinfectious tubal damage, post surgical adhesion formation, and endometriosis-related adhesions.

The normal process of captation of the oocyte requires a series of prerequisites: the ovarian surface free from adhesions, the fimbrial-ampullary portion of the tube free to embrace the ovary and, beside tubal patency, a normal activity of the ciliated and secretory cells of the tubal mucosa. Furthermore, the muscular layer of the tube must be undamaged and able to contract.

In recent years the treatment of tubal infertility has witnessed a shift from tubal reconstructive surgery to in vitro fertilization–embryo transfer techniques (IVF). Due to the wider availability of assisted reproductive technologies, the number of women with mechanical infertility treated by reconstructive surgery has decreased, most couples being referred to IVF.

Reproductive surgery is performed with the aim of allowing ovum pick-up by restoring normal anatomic relationships between the fimbriae and the ovary. However, even though reproductive surgery may be successful in restoring normal anatomy, it may not be able to restore normal function of the damaged tubal mucosa.

The percentages of success of the surgical treatment are therefore strictly correlated with the type of preexisting tubal damage, independently of the surgical technique performed.

Recent refinements of laparoscopic instrumentation and increased surgical skills in operative laparoscopy allow laparotomy to be avoided in most instances.

The advent of salpingoscopy, a technique that allows direct visual evaluation of the tubal mucosa, has allowed improved selection of patients who are candidates for tubal reconstructive surgery by identifying the patients with good reproductive prognosis.

The following is an analysis of the various indications to tubal surgery according to the level (proximal or distal) and type of tubal pathology.

Proximal tubal occlusion (PTO)

Lack of passage of the contrast medium at the level of the intramural–isthmic portion of the fallopian tube during an hysterosalpingogram (HSG) or a laparoscopy with chromopertubation may be due to a true occlusion consequent to postinfectious fibrosis or to an obstruction due to technical artifacts, a spasm of the uterine tubal ostium, a valve mechanism determined by an area of endometrial thickness (focal hyperplasia), or to plugs of amorphous material.

Bilateral PTO is a relatively infrequent finding. We reported [4] that out of 665 patients undergoing laparoscopy with chromopertubation for primary or secondary infertility, only 35 patients (5%) had bilateral PTO confirming a previous HSG finding (25 patients bilateral, 10 unilateral with the contralateral tube either distally occluded or absent). Of these patients, 17 refused any further treatment. After a mean follow-up of 25 months, 3 (18%) of these patients spontaneously conceived an intrauterine pregnancy; 4 out of 5 patients who underwent a repeated HSG had bilateral tubal patency. Therefore, the diagnosis of bilateral tubal occlusion proved to be incorrect in 7 out of 17 patients (42%).

Furthermore, with regard to the etiology of temporary proximal tubal obstruction, a recent paper [5] hypothesizes that small air bubbles, but more likely tubal kinking, may be an explanation of these findings in the patients undergoing HSG in the supine position. In a series of 156 patients, unilateral PTO was diagnosed in 15% of patients (24 of 156) and bilateral PTO in 3% (4 of 156). Rotating the patient such that the obstructed tube was inferior to the uterus resolved 63% of the unilateral PTO, likely by unkinking the tube at the uterotubal junction, thus dramatically lowering the resistance to the flow of contrast medium. The same manoeuvre was less effective in bilateral PTO, where 25% of the more dependent tubes became patent. Still, this report offers an important contribution to the explanation of “reversible” PTO. The possibility that some PTO are obstructions and not true occlusions is supported by the study of Sulak et al. [6] who in 1987 reported on 18 patients who were found to have bilateral PTO by both HSG and subsequent laparoscopy with chromopertubation and therefore underwent resection of the occluded tubal segment and anastomosis. Resected tubal segments were studied histologically, and in 11 of the 18 cases no tubal occlusion could be demonstrated. In six cases (three with occlusion and three with apparent patency) the tubal lumen contained an amorphous material of unknown etiology, often appearing to form a cast of the tube. The authors were the first to report on such “plugs” and speculated that, if they cause tubal obstruction, this would explain previously published findings of high pregnancy rates in infertility patients after HSG. The suggested mechanism would be, among others, dislodging of tubal mucus plugs.

In 1987 Thurmond et al. [7] described their technique for selective salpingography and fallopian tube recanalization that has since then been widely used to improve diagnosis by injecting contrast medium through a catheter placed in the tubal ostium. This technique allows differentiation of tubal spasm from true occlusion, and can be performed in the same session as the hysterosalpingographic examination that fails to opacify the tubes. In fallopian tube recanalization, a catheter and guide wire system is used to clear proximal tubal obstruction by amorphous debris.

A review [8] evaluating results with this technique in 1,466 patients reports a successful recanalization of the proximal fallopian tube in 71–92% of recanalization attempted. Pregnancy rates after the procedure have been variable among series, with an average rate of 30% during follow-up.

In a retrospective study, Al-Jaroudi [9] et al. have recently evaluated the reproductive performance of women after selective tubal catheterization. Ninety-eight infertile women with hysterosalpingographic findings of PTO underwent a repeat hysterosalpingography examination before selective tubal catheterization. Bilateral tubal patency was documented in 14 patients and patency of one of the tubes in 12 others. PTO was confirmed in 72 patients. Successful recanalization of both tubes was achieved in 25 patients (34.7%) and successful recanalization of at least one tube was achieved in 44 patients (61.1%). Of the 72 patients who underwent selective tubal catheterization, 23 conceived (31.9%).

The cumulative probability of conception was 28%, 59%, and 73% at 12, 18, and 24 months of follow-up, respectively.

The few patients with failure of tubal recanalization may likely have true occlusion caused by fibrotic scarring of the tube from salpingitis, endometriosis, or surgery. Microsurgical resection and tubocornual anastomosis continue to be the standard of care in these cases [10].

In a review of nine case series including 187 patients with PTO, we reported [11] a 49% term pregnancy rate per patient, with a 4% risk of ectopic pregnancy after microsurgery by laparotomy.

In 1987, Patton et al. [12] reported on a series of 27 patients with a postpelvic inflammatory disease (PID) bilateral PTO or PTO of the single remaining tube diagnosed both at HSG and laparoscopy with tubal perfusion. Patients were not excluded on the basis of age, extent of tubal disease, duration of infertility, tubal length, or history of prior operation. After an extended follow-up (mean 1,714 days) the possibility of conception was of 46%, 65%, and 69.3% within 1, 2 and 3 years from surgery, respectively.

The probability of a conception resulting in a live birth was 27%, 47%, and 53.2% at 1, 2, and 3 years after surgery, respectively. When only patients who did not have a previous surgery for infertility were considered, the conception rate was 75% with a live birth rate of 58% after 3 years.

Distal tubal occlusion (DTO)

Salpingoneostomy utilizing microsurgical techniques, first described by Swolin [17] in 1967, has been for years the procedure for the treatment of distal tubal occlusion.

In a literature review of 14 series, including 1,275 patients, we reported [18] a cumulative intrauterine pregnancy rate with microsurgical salpingoneostomy by laparotomy of 326/1275 (26%). The cumulative term pregnancy rate was 239/1158 (21%), the cumulative spontaneous abortion rate 54/1125 (5%), and the cumulative ectopic pregnancy rate 96/1245 (8%).

Ten studies, including 1,128 patients, had complete information on pregnancy outcomes. The cumulative pregnancy rate per patient was 371/1128 (33%). Of the pregnancies, 77% (284/371) were intrauterine, 61% (227/371) were term pregnancies 15% (55/371) were spontaneous abortions, and 23% (87/371) were ectopic pregnancies.

A recent review evaluated five nonrandomized control studies that compared laparoscopic and open microsurgical tubal surgery for treatment of DTO [19]. No significant difference was observed in the intrauterine pregnancy rate between the two groups (laparotomy group: 138/478, 28.9%; laparoscopy group: 104/336, 30.9%; combined OR 1.32 [95% CI 0.58–3.02]).

In three of the studies, sufficient information was given to compare surgical techniques used at different stages of tubal disease.

Overall, there was no significant difference in the intrauterine pregnancy rate in laparatomy versus laparoscopy in mild tubal disease (laparotomy group: 83/253, 32.8%; laparoscopy group: 96/243, 39.5% OR 1.06 [95% CI 0.42–2.70]).

For patients with severe stage tubal disease, there was a significantly increased intrauterine pregnancy rate in the laparotomy group (47/210, 22.4% versus 6/86, 6.98%, OR 2.88 [95% CI 1.16– 7.16]).

Subsequently, the principles of microsurgery were introduced in the laparoscopic approach for the treatment of distal tubal disease.

Several classifications have been proposed in order to identify the patients that may most benefit from tubal reproductive surgery in DTO. Various parameters are considered, such as the type and extension of periadnexal adhesions, the degree of tubal occlusion, and the status of the tubal mucosa.

In 1988, the American Fertility Society proposed a scoring system in order to allow the comparison of results obtained from different authors. This was based on the following parameters: type and extension of the adhesions and, in addition, for the classification of distal tubal occlusion, thickness and rigidity of the tubal wall, distal ampullary diameter, and the percentage of mucosal folds preserved at the neostomy site. The importance of intraoperative salpingoscopy to visualize the entire length of the ampullary mucosa was recognized. However, salpingoscopic findings were not included in the scoring system as salpingoscopy was being practiced in very few centers.

Numerous prospective studies have recently demonstrated that, also in the case of distal tubal occlusion, the most important prognostic factor is represented by the status of the tubal mucosa. It is therefore important to identify the patients with normal tubal mucosa by means of salpingoscopy.

In fact, prospective studies have demonstrated that patients with normal tubal mucosa (grades I and II) will have a term pregnancy rate of 65% after salpingoneostomy (compared to 25% obtained in nonselected patients).

Studies of Brosens and Marana [14–16] report that in cases of distal tubal occlusion, the percentage of patients with normal tubal mucosa range from 35–45%. Therefore, in cases of DTO, 35–45% of the patients have a normal tubal mucosa, with a 65% chance of a term pregnancy rate after a laparoscopic salpingoneostomy.

Most of the pregnancies occur in 12–18 months.

In conclusion, based on these findings, in cases of DTO, our current approach would be a diagnostic laparoscopy with salpingoscopy. Laparoscopic salpingoneostomy would then be performed in the patients with normal tubal mucosa.

IVF results

According to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry published in 2007 [21], reporting the results of 79,042 IVF cycles (with and without ICSI) performed in 2001, the percentage of clinical pregnancy was 32.8% per initiated cycle, 38.2% per retrieval, and 40.6% per transfer. The delivery rates were, respectively, 27.2%, 31.6%, and 33.6%. The cancellation rate was 14.1%; the clinical pregnancy loss was 17.2% and the ectopic pregnancy rate 1.8%.

Of the deliveries, 64.1% were singletons, 32.0% were twins, 3.7% were triplets, and 0.1% were greater than triplet deliveries.

According to the European Society of Human Reproduction and Embriology Registry published in 2007 [22], reporting the results of 365,000 ART cycles performed in 2003, the clinical pregnancy rate per retrieval and per transfer were, respectively, 26.1% and 29.1% for IVF, whereas they were 26.5% and 28.7%, respectively, for ICSI. Incomplete data were available for the analysis per cycle and for term deliveries.

Of the deliveries, 76.7% were singleton, 22.0% were twins, and 1.1% triplets.

The latest results published by the North American and European societies reported here confirm a trend toward better results for assisted reproductive techniques with passing years. The same improvements are not present for the results of tubal surgery. A major improvement with this respect has, however, been made in the field of better patient selection for tubal surgery, following which, for example, as previously discussed, a global 25% pregnancy rate in nonselected patients with DTO can be brought up to 65%. In the final section of this review, a personal view on the comparison between IVF and tubal surgery is reported.

Discussion

It is important to underline that while IVF is a ‘palliative’ technique, which means that it does not eliminate the problem but bypasses it, surgery is curative in the favourable cases with normal tubal mucosa. This allows women to obtain pregnancy naturally, and it is therefore an option for couples with ethical and religious concerns. If successful, surgery allows women to have more than one pregnancy without further treatment, with an abortion rate similar to that of the normal population.

Indications to IVF for ‘tubal factor infertility’ may not be correct as this diagnosis often proves to be fallacious. In fact, we have demonstrated that the diagnosis of PTO has a high false positive rate due to technical problems, valve mechanism, intraluminal debris, or chronic inflammation. The diagnosis of DTO, although generally accurate, may sometimes be mimicked by ampullary diverticulae, due to a congenital defect of the myosalpinx, that do not need reconstructive surgery and are not incompatible with pregnancy [23].

In a recent study, Hennelly et al. [24] sent a questionnaire to each patient who was known to have delivered an infant after an IVF or ICSI treatment at their university-based assisted reproduction unit and who had not returned for further therapy. Five hundred fifty questionnaires were sent out. Five hundred thirteen (94%) responses were received and analyzed. One hundred six (20.7%) of the 513 respondents reported that they had had a subsequent spontaneous pregnancy. All the pregnancies occurred within 2 years of the IVF/ICSI pregnancy success. The authors underlined that patients entered the program only if they had a valid indication for IVF/ICSI. These patients truly undertook IVF as a last resort. Therefore, it was surprising to find that 19 out of 128 patients with a diagnosis of tubal factory infertility (14.8%) later conceived spontaneously.

With respect to financial concerns, it should be considered that, unlike in the USA, in Italy as in other European countries, operative laparoscopy, even for infertility, is fully subsidized by the government health service when performed in a public hospital. On the contrary, IVF is mainly performed in private centres and is not reimbursed either by the government or private insurances.

The risks of tubal surgery are very low and are due to the known complications of anesthesia and surgery. Although low, the risk of complications is present even in IVF, with a reported prevalence of serious cases of ovarian hyperstimulation syndrome of 14 per 1,000 women after the first cycle and 23 per 1,000 after a mean of 3.3 treatments in the 9,175 patients followed by the National Research and Development Centre of Finland [25].

With regard to cumulative pregnancy rate after IVF, in a recent paper Sharma et al. [26] reported a cumulative live birth rate of 66% following four cycles of IVF. However, the discontinuation rate was very high during the study. Only 36% of patients continued treatment after the first unsuccessful attempt (dropout rate 74%); the dropout rate was 61% after the second attempt, and 69% after the third attempt.

Lack of success and psychological stress are the main factors in influencing the decision to discontinue treatment with increasing number of attempts [27]. A prospective, cohort study reported that an unexpectedly high percentage of couples who performed IVF discontinued the subsidized treatment before the three cycles that were offered. The majority of these discontinuations were due to psychological stress [28].

Concern has recently been expressed about the health of the children conceived after IVF [29, 30]. It has been reported in singleton ART infants a two-fold increase in risk of perinatal mortality, low birthweight, and preterm birth, about a 50% increase in small for gestational age, and a 30–35% increase in birth defects [31]. The same Centre for Child Health Research evaluated all papers published by March 2003 with data relating to the prevalence of birth defects in infants conceived following IVF/ICSI compared with spontaneously conceived infants [32]. Meta-analyses of seven reviewer-selected studies and of all 25 studies identified as suitable for inclusion in a meta-analysis suggest a statistically significant 30–40% increased risk of birth defects associated with ART. The authors conclude that this information should be made available to couples seeking ART treatment.

The guidelines recently approved by the Genetics Committee and the Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynecologists of Canada for counselling of Canadian women using ART recommend: pregnancy achieved by IVF with or without ICSI are at higher risk for obstetrical and perinatal complications than spontaneous pregnancies; singleton pregnancies achieved by ART are at higher risk than spontaneous pregnancies for adverse perinatal outcomes, including perinatal mortality, preterm delivery and low birth weight; ART has a significant risk of multiple pregnancies; risks of multiple pregnancies include higher rates of perinatal mortality, preterm birth, low birth weight, gestational hypertension, placental abruption, and placenta previa; and that further epidemiologic and basic science research is needed to help determine the etiology and extent of the increased risks of congenital abnormalities associated with ART [33].

An increased risk of congenital malformations in relation to IVF even in singleton infants has been confirmed by a recent review analysing the medical literature update to 2006 [34].

In conclusion, in spite of the recent improvements in the success of IVF, tubal reconstructive surgery remains an important option for many couples. In referral centers, surgery should be the first line approach for a correct diagnosis and treatment of tubal infertility. The success of the surgical treatment depends on careful selection of patients using appropriate diagnostic techniques.

Source - https://gynecolsurg.springeropen.com/articles/10.1007/s10397-007-0344-z

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To More Post: Can open tubal microsurgery still be helpful in tubal infertility treatment?

Can open tubal microsurgery still be helpful in tubal infertility treatment?

Abstract

In 30 years, 1,669 patients underwent open microsurgery for tubal diseases. Several techniques like adhesiolysis, reanastomosis, fimbrioplasty, salpingoneostomy, proximal reconstruction, isthmo-ostial anastomosis and reimplantation are described. Results were excellent for patients with a favourable prognosis (1,517 patients) and with very high pregnancy rate: 80% pregnancies with delivery for tubal reversal, 68% for proximal diseases, 75.1% for fimbrioplasty and 55% for salpingoneostomy. Risks of ectopic pregnancy were very low: 1.5% for tubal reversal (because the tubes were healthy), 4% for proximal diseases, 4% for fimbrioplasty and 6.7% for salpingoneostomy. Results were very low for patients with a poor prognosis (152 patients): 10% pregnancies with delivery for distal diseases, less than 20% for proximal diseases and 22% ectopic pregnancies. Open microsurgery can still be helpful in treating tubal infertility: results are better than those obtained with laparoscopic reconstructive surgery and better than those obtained with in vitro fertilization for patients with a favourable prognosis. Patients are only operated one time and can have several pregnancies. Open tubal microsurgery is a minimal invasive surgery and saves costs (it requires a small number of instruments and minimises sutures; patients can return home 4 days after surgery, at the latest). Results on fertility are very favourable.

Between 1977 and 2007, 1,669 patients underwent a minilaparotomy for tubal diseases. Minilaparotomy means a laparotomy with minimal tissue injury, applying microsurgical principles and procedures.

One of the first principles we followed was the temporary but absolute contraindication for surgery in case of active infection and active inflammation (for example endometriotic red lesions).

We also applied the following principles:

• gentle handling of tissues

• atraumatic manipulation of the tubal serosa and mucosae, of the ovary and of the peritoneum

• selective bipolar coagulation: only the vessels (and not the surrounding area) must be dessicated by fine bipolar microelectrodes

• continuous irrigation to keep the surgical area clear at all times and to avoid the tissue from drying out (and especially the tubal serosa and the ovary)

• perfect protection of the abdominopelvic cavity against infection risk using the sterile “wound drape”

• complete resection of pathologic tissues

• complete restoration of the serosa: closure of all peritoneal defects to avoid formation of de novo adhesion and recurrence of previous adhesion (peritoneal defects in case of adnexal disease due to previous infection or inflammation do not scar easily and quickly because the subserosal tissue is not a normal tissue; it is usually rich in inflammatory cells). A peritoneal closure with fine material and inverted stitches scars better and faster than a large defect without peritoneal closure

• use of very fine resorbable sutures 7/0 and 8/0

• last, use of a well mastered surgical technique: the surgery must be successful the first time. Repeat surgery never gives favourable results

Preoperative investigations

All patients had complete investigations: hormonal analysis, male analysis, hysterosalpingography, hysteroscopy and sometimes recanalisation, diagnostic laparoscopy with blue dye test. Results were written down before surgery and then compared with operative images (all surgery were taped first with 8-, then 16-mm film camera Beaulieu, and then with 3-CCD Sony DXC 930 P video camera) and with postoperative histological examination of all resected lesions. The analysis is therefore not entirely retrospective.

Preoperation and per operation procedures

Prior to the laparotomy, a Pezzer catheter is introduced into the uterine cavity. This catheter is brought into sterile fields and allows the preoperative injection of sterile dilute methylene blue solution for verification of the tubal patency. After a short Pfannenstiel incision (6/7 cm), we protect the pelvis with a “wound-drape”. The uterus and adnexa are elevated by packing the Douglas cul-de-sac with moistened compresses. Continuous irrigation of the surgical area using a physiological salt solution mixed with noxytioline and corticoid (permanently evacuated by a Redon drain positioned in the Douglas pouch) keeps the operating area always clear. It keeps the tissues always moistened to prevent tissue drying, avoids formation of adhesion and allows for bipolar coagulation. Extreme gentleness is exercised. Tissue traumatism is prevented by the gentle handling the tubes and the ovary with fingers rather than sharp instruments. At the end of the operating time, a meticulous cleaning of the pelvic cavity is useful.

For 30 years, several peritoneal instillates were used: Ringer's lactate which is not compatible with noxytioline, 30% dextran 70, Intergel, icodextrin 4% solution, etc., but we think it is not necessary to use instillates if the microsurgical technique is perfect: minimal tissue traumatism, perfect haemostasis, no tissue necrosis, no infection risk. We do not use these instillates in case of tubal reversal because the tubes are healthy; there is no peritoneal defect and no risk of adhesion.

Conclusions

Open tubal microsurgery is really a minimal invasive surgery and can still be an excellent technique for most of tubal diseases. There is no competition between tubal microsurgery and IVF; they are complementary.

For tubal reversal, microsurgery must be performed first because pregnancy rate is very high. IVF cannot give same results, especially when 45% of patients are more than 40 years old (patients above 40 years of age had tubal reversal because they were still fertile, and their tubes were still healthy). There was no significant difference with regards to age on pregnancy results (but we did not operate patients above 43 years old). For distal and proximal diseases, patients of 40 years old are usually patients with poor prognosis and cannot be operated (distal lesions can be quite old and can create the atrophy of the mucosae; old proximal disease can be extended). In the future, laparoscopic reversal could present same results for pregnancy with delivery but ectopic pregnancy rate must be reduced by use of fine sutures (8/0), fine instruments and best technique of suturing.

For distal tubal lesions, more than 50% of the patients have a poor prognosis. These tubes must be resected in order to increase favourable results for IVF. On the other hand, distal lesions with favourable prognosis must be operated first. In case of failure, IVF can be performed 1 year after surgery (Table 1). Laparoscopic surgery cannot presently give same results because laparoscopic adhesiolysis is still too traumatic, and electrocoagulation damages too much tubes and ovaries. It is also important to use an optimal suturing technique.

For proximal lesions, about 30% of patients have poor prognosis. They must have IVF, but it is usually uterine adenomyosis extending to the tubes; and IVF does not yield favourable results. Proximal lesions with favourable prognosis must be treated first by microsurgery, followed by IVF 1 year later if the patient is not older than 38 years of age (Table 3). In case of proximal lesions with favourable prognosis, open microsurgery is easier and more precise than laparoscopic microsurgery, even when assisted by a robot.

Source -  https://gynecolsurg.springeropen.com/articles/10.1007/s10397-010-0556-5

Dr shweta kaul jha is one of the Best IVF specialist in indore, providing a wide variety of infertility treatments as well as in vitro related procedures such as IVF-ICSI, genetic testing, preserving fertility in cancer patients, and many more at affordable ivf cost in indore. Book an appointment call 88890-16663 or visit www.carewomenscentre.com

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To More Post: Lipomesosalpinx: a rare possible missed tubal factor of infertility