Diagnosis and treatment of early-stage endometriosis by Transvaginal Hydro laparoscopy.

Background: Transvaginal Hydro Laparoscopy (THL) is known as a minimal invasive procedure allowing endoscopic exploration of the female pelvis. Objective: To evaluate the possibilities of the THL as a tool for early diagnosis and treatment of minimal endometriosis. Materials and Methods: A retrospective study of a consecutive series of 2288 patients referred for fertility problems to a tertiary centre for reproductive medicine was undertaken. Mean duration of infertility was 23.6 months (SD ±11-48), mean age of patients was 31.25 (SD± 3.8y). With normal findings at clinical and ultrasound examination patients underwent, as part of their fertility exploration, a THL. Main outcome measures: Evaluation of feasibility, identified pathology and pregnancy rate. Results: Endometriosis was diagnosed in 365 patients (16%); the localisation was higher on the left side (n=237) than on the right side (n=169). Small endometriomas, with diameters between 0.5 and 2 cm, were present in 24.3% (right side in 31, left side 48 and bilateral 10). These early lesions were characterised by the presence of active endometrial like cells and a pronounced neo-angiogenesis. Destruction of the endometriotic lesions with bipolar energy resulted in an in vivo pregnancy rate (spontaneous/IUI) of 43.8% (CPR after 8 months: spontaneous 57.7%; IUI/AID 29.7%). Conclusion: THL allowed in a minimally invasive way an accurate diagnosis of the early stages of peritoneal and ovarian endometriosis with the possibility of offering treatment with minimal damage. What is new?: This is the largest series reporting the usefulness of THL for the diagnosis and treatment of peritoneal and ovarian endometriosis in patients without obviously visible preoperative pelvic pathology.

Systematic use of transvaginal hydrolaparoscopy as a minimally invasive procedure in the exploration of the infertile patient: results and reflections.

BACKGROUND: The aim of this study was to evaluate the added value of transvaginal hydrolaparoscopy (THL) in the investigation of the infertile patient. METHODS: A retrospective cohort study, based on records from 01/09/2006 to 30/12/2019 was undertaken in a tertiary care infertility centre. THL was performed in 2288 patients. These were patients who were referred for endoscopic exploration of the female pelvis as part of their infertility investigation. In 374 patients with clomiphene-resistant polycystic ovary syndrome (PCOS), ovarian capsule drilling was also performed. The outcome objectives of this study included the evaluation of the added diagnostic value of THL as well as the feasibility and safety of the visual inspection of the female pelvis using this technique. RESULTS: Of the 2288 procedures failed access to the pouch of Douglas occurred in in 23 patients (1%). The complication rate was 0.74%, due to bowel perforations (n= 13) and bleeding (n= 4) requiring laparoscopy. All bowel perforations were treated conservatively, with 6 days of antibiotics, and no further complications occurred. Findings were normal in 49.8% of patients. Endometriosis was diagnosed in 366 patients (15.9%); adhesions were present in 144 patients. CONCLUSIONS: THL is a minimally invasive procedure, with a low complication and failure rate, providing an accurate visual exploration of the female pelvis in a one-day hospital setting. When indicated, minimally invasive surgery is possible in the early stages of endometriosis and for ovarian capsule drilling in patients with clomiphene-resistant PCOS.

Transvaginal endoscopy and small ovarian endometriomas: unravelling the missing link?

The incidence of endometriosis in the infertile female is estimated to be between 20 and 50 %. Although the causal relationship between endometriosis and infertility has not been proven, it is generally accepted that the disease impairs reproductive outcome. Indirect imaging techniques and transvaginal laparoscopy now offer the possibility of an early stage diagnosis. Although it remains debated whether the disease is progressive, treatment in an early stage is recommendable as it carries less risk for ovarian damage, hence premature ovarian failure. Under water, inspection with the technique of transvaginal hydrolaparoscopy (THL) accurately shows the invagination of the ovarian cortex as minimal superficial lesions but with the presence of well-differentiated endometrial like tissue at the base, the lateral walls and especially the inner edges of the small endometrioma. An inflammatory environment is responsible for the formation of connecting adhesions with the broad ligament and lateral wall with invasion of endometrial-like tissue and formation of adenomyotic lesions. In around 50 % of the small endometriomas, adhesiolysis is necessary at the site of invagination with opening of the cyst, to free the chocolate content and hereby recognize the underlying endometrioma. The detailed inspection of these early-stage endometriotic lesions at THL reunites the hypothesis of Sampson with the observation of Hughesdon.

Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition.

Early stage management of ovarian endometrioma to prevent infertility.

There are now convincing data showing that cystectomy of the endometrioma is not only no cure of infertility, but may harm follicle reserve. The question arises why is cystectomy for an endometrioma, in contrast with other -benign cysts, a risk for follicle reserve and how can ovarian damage be prevented. Surgical specimens of ovaries with endometrioma in situ show in the majority of cases manifestly a combined -extra-ovarian and intra-ovarian pathology with the cortex invaginated to form a pseudocyst. The extra-ovarian pathology includes endometrial lining of the cortex, bleeding and adhesions with surrounding tissues. The intra-ovarian pathology is characterized by microscopic stromal implants, fibrosis, smooth muscle metaplasia and -arteriosclerosis, all affecting follicle reserve in the endometrioma bed. Clinically, ovarioscopy allows differential diagnosis (e.g. luteal cyst) and evaluation of the degree of fibrosis and darkening of the cortical wall. Transvaginal colour Doppler sonography can demonstrate the presence and extent of devascularisation in the endometrioma bed. Given this reality, surgery should be based on evaluation of the pathology of the endometrioma bed, but not on the mere size of the chocolate cyst. The main clinical problem is indeed the delayed diagnosis and consequently advanced irreversible cortical damage. Therefore, the sooner endometriomas are diagnosed, the better, because it increases the chances that vascularisation of the endometrioma bed is preserved. Finally, ablation, but not excision is the treatment of choice. The diagnosis of endometriosis is traditionally based on laparoscopy, but in a sexually active adolescent transvaginal endoscopy can be proposed.

A prospective randomised study comparing a GnRH-antagonist versus a GnRH-agonist short protocol for ovarian stimulation in patients referred for IVF.

OBJECTIVE: To compare two short protocols for ovarian stimulation in IVF cycles using an antagonist and an agonist short protocol. The outcomes studied were dosis rec FSH needed, days of stimulation, number of oocytes retrieved and pregnancy outcome. METHODS: A prospective randomised study design. INCLUSION CRITERIA: first or second IVF attempt in women younger than 40 years. In the agonist protocol (Suprefact®) nasal spray was used. In the antagonist protocol (Orgalutran)® was started as soon as at least 1 follicle of 12 mm was visualized on ultrasound. RESULTS: 160 cycles were included in the study: 80 in the antagonist group and 80 in the agonist group. A higher dosis of recombinant FSH (rec FSH) was used for stimulation in the antagonist group (1897 IU versus 1655 IU). Pregnancy rate per ET in the antagonist group was 37% with an ongoing pregnancy rate of 21%/ET and an -implantation rate of 22%; versus respectively 39%, 20% and 22% in the agonist treated group. Live birth rate per started cylce was 19% in the antagonist group versus 20% in the agonist group. CONCLUSION: This study shows that implantation rates, ongoing pregnancy rates and live birth rates are equal in both groups. An identical number of oocytes was retrieved, with no difference in duration of the stimulation although a higher dosis of rec FSH was needed in the antagonist group.

Critical reappraisal of embryo quality as a predictive parameter for pregnancy outcome: a pilot study.

AIM OF THE STUDY: Pilot study to analyse the efficacy and embryo morphology using a new human embryo culture medium (GM501) versus the conventional used medium (ISM1). METHODS: Over a four-month period, all patients at the Leuven Institute of Fertility and Embryology (LIFE) were -randomly allocated to have their embryos cultured in either the standard sequential culture medium ISM1 (control) or in a new universal medium (GM501) (study group). Primary outcome parameters were clinical pregnancy and live birth rate. The secondary outcome parameter was the correlation of embryo fragmentation rate with pregnancy outcome. RESULTS: We did not observe any differences between the ISM1 control group and GM501 study group with regard to fertilization, pregnancy, implantation rates, ongoing pregnancy, and babies born. The number of embryos with a minimal fragmentation rate (less than 30%) was significantly higher in the GM501 study group. CONCLUSION: Although a significant higher embryo fragmentation rate was seen in In vitro culture of embryos in GM501, pregnancy outcome results were comparable to those of embryos cultured in ISM1. According to our results the value of embryo morphological criteria as a parameter for pregnancy outcome should be examined and discussed again.

Transvaginal laparoscopy.

Transvaginal laparoscopy (TvL) offers an alternative to standard diagnostic laparoscopy in subfertile patients without obvious pelvic pathology. With a specially developed needle-trocar system, access to the pouch of Douglas is gained through a needle puncture of the posterior fornix. Performed under local anaesthesia or sedation with the patient in a dorsal decubitus position and using prewarmed Ringer lactate as a distension medium, TvL allows complete exploration of the tubo-ovarian structures without supplementary manipulation. The combination of transvaginal sonography and transvaginal endoscopy, including minihysteroscopy, TvL, salpingoscopy and chromopertubation test, permits the most complete exploration of the reproductive tract and can be used as a first-line investigation of female fertility in a one-stop infertility clinic. As the transvaginal route offers easy access to the tubes, ovaries and fossa ovarica, some operative procedures are possible. However, in the absence of a panoramic view, these will be limited to minor interventions.

Belgian legislation and the effect of elective single embryo transfer on IVF outcome.

In order to reduce the number of multiple pregnancies following IVF, the Belgian government agreed to reimburse laboratory expenses for six IVF cycles up to the age of 42 years, in exchange for restriction of the number of embryos replaced. Data on assisted reproduction outcome before and after the introduction of this new legislation were analysed retrospectively in terms of implantation, pregnancy and multiple pregnancy rates. After the introduction of the new law, the percentage of single embryo transfer increased from 14 to 49%. Implantation rates were 25.9 and 23% respectively. There was no difference in the overall pregnancy rate before and after the introduction (36 versus 37%). Twin pregnancies, however, decreased from 19 to 3%. These findings indicate that elective single embryo transfer significantly decreases the twin pregnancy rate without a reduction in the overall pregnancy rate.

Endometriosis: modern surgical management to improve fertility.

Endometriosis is a pleiotropic reproductive condition and the lesions visualized at laparoscopy are only one aspect of this disease process. At present, there is no evidence that surgery for endometriosis can cure infertility. The most important surgery in infertility is ovarian surgery. It is generally accepted that, in most cases, the invagination of the cortex results in the formation of an endometriotic pseudocyst. As a consequence, primordial follicles are present at the base of the cyst. Since surgery is of limited value, the utmost care has to be given to conservation of the patient's fertility. Ablative surgery offers advantages over excision of the cyst in terms of less adhesion formation and better preservation of the ovarian reserve. The ablative eversion technique differs from fenestration and drainage by its access through the site of inversion and resection of the fibrotic ring. Using the new technique of transvaginal hydrolaparoscopy, access to the site of pathology in the fossa ovarica is facilitated. Furthermore, the aqueous distension medium keeps the organs afloat and provides a clear delineation between the organs and adhesions allowing atraumatic reconstructive surgery.

Hydrosalpinx and ART: hydrosalpinx--functional surgery or salpingectomy?

The debate on the effect of the hydrosalpinx on medically-assisted reproduction has demonstrated the importance of understanding the complex pathophysiology of the hydrosalpinx in outlining the principles of its clinical management, whether it is by functional surgery or IVF, preceded or not by salpingectomy. New endoscopic techniques are available to accurately assess, both in the operating room and the office, the quality of the tubal mucosa. The direct endoscopic evaluation of the tubal mucosa in hydrosalpinges is at present the most reliable technique to select between functional surgery and preventive salpingectomy. In future, prospective randomized studies on salpingectomy will benefit greatly from accurate clinicopathological data.

A decade of salpingoscopy.

With the introduction of the salpingoscopy of the tubal ampullary mucosa in the 1980s, this diagnostic endoscopic examination not only disclosed an exciting world of sharp and detailed in vivo images of the actual site of human fertilization. Its systematic use in the assessment of the tubal factor in subfertile couples also provides specific, clinically relevant and prognostically valuable information, since it clearly demonstrates the presence or absence of anatomical distortions, especially adhesions between and destruction of mucosal folds, on a micro-endoscopic, i.e., mucosal level. The routine salpingoscopy of a free, patent tube is easy to perform and the procedure then takes about 10 min for both sides. In contrast with hysterosalpingography, a proximal (e.g., tubocornual or isthmic) block does not prevent us from examining the ampullary mucosa with the salpingoscope, whereas a small incision at the site of the occlusion with one of the techniques of operative laparoscopy, enables the inspection of the mucosa of a hydrosalpinx. With salpingoscopy, and using a simple classification system, a trained endoscopist can evaluate the sequelae of tubal inflammatory disease and their impact on fertility nearly as efficiently as with mucosal microbiopsies and they can direct their patients accordingly, either towards reconstructive (micro)surgery or towards medically assisted reproduction. In case of a tubal pregnancy, the effort to salpingoscopically evaluate both the affected and unaffected side may help to understand the underlying ethiology of the ectopic. Since patency and a normal appearance of the fimbriated end surely do not imply the absence of endoluminal pathology, it is advisable to select only salpingoscopically normal tubes to perform tubal transfers of gametes, zygotes or embryos. In the still ongoing discussion regarding preventive salpingectomy prior to IVF-ET in case of a uni- or bilateral hydrosalpinx, blind victimization of the Fallopian tube can in our opinion be avoided by a proper endoscopic selection of cases.

Reconstruction of the ovary containing large endometriomas by an extraovarian endosurgical technique.

OBJECTIVE: To describe and evaluate the surgical treatment of large ovarian endometriomas by an extraovarian endosurgical technique. DESIGN: Prospective case series study. SETTING: University center and tertiary referral center for endoscopic surgery. PATIENTS: Patients with large ovarian endometriomas. INTERVENTION: A two-step endosurgical procedure: the first step is a combined diagnostic and operative procedure confirming the diagnosis and preparing the involution of the pseudocyst and the second step includes adhesiolysis and superficial coagulation of the inverted cortex. MAIN OUTCOME MEASURES: Operative findings and recurrence of endometriomas in the operated ovaries. RESULTS: Sixteen patients presenting with 20 large typical ovarian endometriomas were operated using the two-step endosurgical technique. Both steps were performed on 18 endometriomas. One patient with bilateral endometriomas refused the second endoscopic procedure. The long-term follow-up showed no recurrence in the 18 ovaries that were treated by the two-step endoscopic technique. CONCLUSIONS: The two-step extraovarian endosurgical technique can be applied in large typical endometriomas to reconstruct the ovary without excision and is followed by a low recurrence rate.

Clinical value and cumulative pregnancy rates following rigid salpingoscopy during laparoscopy for infertility.

This study was designed to evaluate the routine use of rigid salpingoscopy during diagnostic laparoscopy for infertility, and to relate the morphologic image of the endosalpinx with pregnancy outcome. A total of 158 consecutive patients (232 Fallopian tubes) undergoing a diagnostic laparoscopy for infertility were studied. Salpingoscopy was performed at the time of diagnostic laparoscopy for infertility. The intraluminal image was classified using a simplified classification (class I-V). The relationship between this classification and the cumulative pregnancy rates was calculated using life table analysis. Patients with a normal salpingoscopy (class I and II) had a 71% cumulative pregnancy rate. In the intermediate group (class III) the cumulative pregnancy rate was 34%. No intrauterine pregnancies were observed in the group with severe intratubal pathology (class IV and V). Of the 107 slapingoscopies of patients with endometriosis 105 (98%) were class I or II. However, among patients with pelvic adhesions, only 42% were normal. Nine out of 50 abnormal salpingoscopies were found when no tubal factor was suspected during laparoscopy, without any pelvic adhesions. These results suggest that salpingoscopy is an important tool for detecting mucosal abnormalities, and for eventually referring patients for assisted reproductive technology. Salpingoscopy is usually normal in patients with endometriosis, but in patients with non-endometriotic pelvic adhesions it is not.

Reflections on the way to conduct an investigation of subfertility.

Infertility is a worldwide issue in reproductive health. In view of the World Health Organization's definition of health, the psychological and social consequences of infertility simply cannot be ignored. Prevention of infertility is difficult and does not help the couple seeking medical advice for infertility, whereas efficient treatment for infertility is time consuming, expensive and often unsuccessful. This article reflects on a shortened, yet full investigation of both partners' fertility before any treatment whatsoever, which is indispensable once the decision to help the couple medically has been made. By optimizing the use of modern gynaecological endoscopy within the woman's cycle, an exhaustive infertility investigation can be conducted within the span of two couple-physician contacts, thereby responding to the couple's concern, avoiding loss of time and energy due to inappropriate therapies, and directing the subfertility treatment correctly from the start. Trained gynaecologists can easily conduct this investigation in fertility centres in developed countries, as well as in centres for family planning in developing countries. The investigation can be employed either with an emphasis on diagnosis alone (and then even under local anaesthesia) or, if the necessary infrastructure is available, in combination with operative endoscopy under general anaesthesia where indicated.

Intrauterine insemination: a first-step procedure in the algorithm of male subfertility treatment.

Despite the widespread clinical use of intrauterine insemination (IUI) in the treatment of male subfertility, its therapeutic value remains unclear. The objective of this review was to determine why its efficacy has not been consistently documented in the literature and to give strong evidence supporting the therapeutic merit of ovarian stimulation/IUI in male subfertility treatment. Because (i) this technique is much easier to perform and less expensive than assisted reproduction methods, and seems to be reasonably effective in controlled studies of a male subfertility treatment, and (ii) we may expect that financial resources available for the health care of infertility patients will be limited in the future, we believe that ovarian stimulation/IUI must become the first-line treatment in most cases of male factor subfertility, provided that the multiple gestation incidence can be reduced to an acceptable level.

Polycystic ovarian disease treated by laparoscopic argon laser capsule drilling: comparison of vaporization versus perforation technique.

Forty-four anovulatory women with polycystic ovarian disease (PCOD) were laparoscopically treated with the argon laser. Eighty percent of them were previously resistant to clomiphene citrate therapy. After surgery spontaneous ovulation occurred in 80% of the women. Spontaneous conception occurred in 55% of patients, and another 18% of the women who were previously resistant to clomiphene citrate conceived post-operatively after clomiphene citrate therapy. This gives an overall conception rate of 73% after 18 months (using life table analysis). Two different drilling techniques were used: classical vaporization of the ovarian capsule (22 women), and simple perforation of the ovarian capsule with subcapsular destruction of the ovarian stroma (22 women). No different ovulation or pregnancy rates were observed post-operatively between the two techniques. These results suggest that patients with PCOD can be induced to ovulate, and subsequently conceive, by laparoscopic argon laser treatment. The technique with minimal trauma to the ovarian capsule seems preferable.

The endoscopic localization of endometrial implants in the ovarian chocolate cyst.

OBJECTIVE: To describe the characteristics of the endometrial cyst and to locate the implants for selective biopsy. DESIGN: Prospective study. SUBJECTS: Fifty-one women with one or two ovarian chocolate cysts of 3 cm or more were investigated. INTERVENTIONS: Laparoscopy and random biopsy versus a new technique of ovarioscopy and selective biopsy. MAIN OUTCOME MEASURE: Visual characteristics and histopathology of endometrial cysts. RESULTS: The clinical suspicion of an endometrioma was confirmed in a series of 59 hemorrhagic cysts by histopathology in 89% and 42%, respectively, of typical and atypical cases and in 27% of recurrent chocolate cysts in the presence of postoperative adhesions. The atraumatic technique of ovarioscopy allowed description of the typical characteristics of the inner wall of the endometrioma and location of the active implants for biopsy. Endometrial tissue was obtained by small ovarioscopy-guided biopsies in 82% of the cases versus 42% in large random biopsies. Red lesions were highly significant for a mucosa-type implant and were predominantly located at the site of invagination stigma and adhesions with the pelvic wall. CONCLUSIONS: Endoscopy of ovarian chocolate cysts allows observation of typical features of the wall that differentiates it from other benign cysts of the ovary. Microbiopsies obtained under endo-ovarian endoscopy provided significantly more active, endometrial tissue than random biopsies. The data confirm that in most cases the endometrioma is formed by invagination of the cortex and that active implants are located at the site of invagination. Ovarioscopy is therefore proposed as a useful tool to differentiate in doubtful cases between a hemorrhagic functional and an endometriotic cyst and to select the sites for biopsies.