Thursday 28 November 2019

The infertility trap: how defeat and entrapment affect depressive symptoms.

Abstract

STUDY QUESTION:
Does the perception of failure without a solution or way forward of infertile couples have a mediator role between the importance couples attribute to parenthood and depressive symptoms?

SUMMARY ANSWER:

The perception of failure without a solution or way forward, assessed by feelings of entrapment and defeat, mediates the effect of the importance of parenthood on depressive symptoms of infertile men and women.

WHAT IS KNOWN ALREADY:

Research has documented that the heightened importance of parenthood affects infertile couples' adjustment to infertility and medical treatments. However, it remains unclear which psychological mechanisms and perceptions may underlie the association between having parenthood as a nuclear aspect of life and presenting depressive symptoms related to difficulties in accomplishing that important life goal. Although these links have been scantly addressed in infertility, previous studies have pointed to the role that perceptions of defeat and entrapment have in several psychopathological conditions.

 STUDY DESIGN, SIZE, DURATION:

The study was cross-sectional. Couples pursuing medical treatment for their fertility problems were invited to participate by their doctors in several public and private clinics. Data collection took place between July 2009 and 2011.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

One hundred forty-seven infertile couples consented to participate in the study. Both couple members (147 women and 147 men) completed a set of self-report instruments for the assessment of depressive symptoms, perceptions of defeat and entrapment, importance of parenthood and rejection of a childfree lifestyle. Analyses were conducted through Structural Equation Modeling and followed a dyadic analysis strategy, allowing for controlling the interdependence of the data.

MAIN RESULTS AND THE ROLE OF CHANCE:

The hypothesized tested model showed a very good fit to the data [(χ(2) = 68.45, P = 0.014, comparative fit index = 0.98, standardized root-mean-square residual = 0.06 and root mean square error of approximation = 0.06] and explained 67 and 58% of the variability in depressive symptoms in women and men, respectively. Results revealed that the importance of parenthood does not have a direct effect on depressive symptoms of infertile men and women, but an indirect effect, by affecting the perception of having failed and not being able to solve it or move forward [women: estimate for indirect effect: 0.38 (bias corrected (BC) 95% confidence interval (CI) = 0.25; 0.56; P < 0.001); men: estimate for indirect effect: 0.23 (BC 95% CI = 0.06; 0.40; P = 0.013)].

LIMITATIONS, REASONS FOR CAUTION:

The study was cross-sectional, which does not allow for the establishment of causality. Another limitation is the heterogeneity of the sample, as participants were recruited at various stages of their fertility care. In addition, due to the specific nature of the variables, further studies are needed to establish exactly how the relationship between defeat and entrapment and depression operates, as the mechanism may be bidirectional.

WIDER IMPLICATIONS OF THE FINDINGS:

This study emphasizes the role of perceptions of defeat and entrapment on the psychological adjustment to infertility and assisted reproduction. These emotional processes should be taken into consideration and targeted in psychological interventions of couples undergoing medical treatments for infertility. In fact, although parenthood may be perceived as a core purpose for many couples dealing with difficulties in conceiving, it is only when these difficulties are experienced as failures without a resolution and as inescapable, that couples are prone to develop depressive symptoms.



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Sunday 24 November 2019

Live twin birth after successful treatment of a ruptured heterotopic pregnancy by laparoscopy

Abstract

We report a case of a live twin birth after laparoscopic treatment of a ruptured heterotopic pregnancy. A 29-year-old woman, with a history of right salpingectomy for ectopic pregnancy, became pregnant after transfer of three embryos at in vitro fertilization treatment. At the ninth week of gestation, she was admitted to our clinic with abdominal pain. Ultrasonographic examination revealed a triplet heterotopic pregnancy consisting of an intrauterine twin pregnancy and an ectopic pregnancy in the left fallopian tube. An immediate laparoscopy was planned and left salpingectomy was performed. In the postoperative period, intrauterine twin pregnancy continued uneventfully; at the 35th week of gestation, two healthy infants with birth weights of 2,206 and 2,426 g were delivered. Heterotopic pregnancies must be kept in mind after assisted reproductive techniques. Early diagnosis allows successful laparoscopic treatment without sequel. Laparoscopic surgery is an appropriate method to manage selected patients with heterotopic tubal pregnancy.

Introduction

Ectopic pregnancy (EP) refers to the implantation of a viable ovum outside the uterine corpus. Heterotopic pregnancy (HP) is the simultaneous occurrence of gestations at two or more implantation sites. It is most often manifested as concomitant intrauterine pregnancy (IUP) and EP [1]. Although EP is not uncommon in women of reproductive age, HP is rare in the general population, with an incidence of 1:7,963–30,000 in spontaneous conceptions [2]. The increased incidence of pelvic inflammatory disease (PID), the common usage of ovulation inducing agents, and assisted reproductive techniques (ART) have contributed to the increasing incidence of both multiple gestations and HP in the last decade. The rate of HP after in vitro fertilization (IVF) has been reported to be as high as 1% [2, 3], although it’s true incidence is unknown. Most recent studies exhibit the incidence about 152 per 100,000 pregnancies in ART cycles [4]. Due to the difficulty in the diagnosis, rupture of the tube, bleeding, and the need for emergency operations are seen more often in heterotopic than in ectopic pregnancies. Thus, all pregnancies as a result of ART must be evaluated cautiously. Here, we report a triplet heterotopic pregnancy, which was successfully diagnosed and treated by laparoscopy.

Case

A 29-year-old woman G: 1, P: 0, with unexplained infertility, not to be able to conceive for 3 years, underwent an IVF procedure. She had a history of an EP 3 years ago treated by unilateral right salpingectomy. After initial downregulation using leuprolide acetate 500 μg/day (Lucrin; Abbott, Cedex, Istanbul, Turkey), 225 IU/day of recombinant follicle stimulating hormone (Gonal F; Serono Laboratories) was given starting from the second day of the menstrual cycle. When at least three follicles >17 mm were observed, human chorionic gonadotropin (hCG; Pregnyl; Organon, Cambridge, UK) was administered 10,000 IU i.m. and oocyte retrieval was performed at 35.5 h. Five of eight retrieved oocytes were successfully fertilized by IVF. Two days after oocyte retrieval, three embryos were transferred. Luteal phase support in the form of intravaginal micronized progesterone was given. Serum beta-hCG was 52 IU/mL on day 12 and we deduced intrauterine live twin pregnancy 4 weeks after embryo transfer.

At the ninth week of gestation, she was admitted with abdominal pain. Transabdominal ultrasonography (US) examination revealed intrauterine live twin pregnancy and a left-sided ectopic pregnancy with fetal heart beat. The vital signs of the patient were in normal range. A diagnostic laparoscopy was performed using general anesthesia and the ports were placed in classical locations carefully to protect the uterus. A ruptured left tubal EP was found covered with omentum hanging on the anterior abdominal wall (Figs. 1 and 2). Left salpingectomy was performed successfully. The patient was discharged at the second day after the operation. In the postoperative period, the intrauterine twin pregnancy continued uneventfully with no unusual aspect of the prenatal care and she delivered two healthy infants at the 35th week of gestation with birth weights of 2,206 and 2,426 g.

Discussion

HP is a rare entity in spontaneous cycles; however, its incidence has risen with the widespread use of ART. Although most ectopic gestations in HPs occurring after ART are tubal, 10.8% are extratubal [5] and more difficult to diagnose. The beta-hCG may continue to rise normally and US may be unreliable in the presence of a normal intrauterine gestation especially in HPs. The intermittent unilateral pain can be attributed to a hemorrhagic corpus luteum, or a small degree of ovarian hyper stimulation [6]. Therefore, we need to have better evaluation of the adnexa when pain is out of proportion of what is expected in a woman with IUP. Most cases are missed on their initial examination, and patients frequently present with symptoms of rupture before the diagnosis is ultimately made, as in this case. Therefore, keeping its high incidence after ART in mind, careful surveillance of extrauterine structures at the first US examination is essential in pregnancies achieved after ART.

Different mechanisms may predispose to development of HP after ART cycles. More embryos transferred by ART procedures increase both multiple gestation and EP incidences [7]. Other factors predisposing to ectopic gestation are previous tubal damage caused by PID, endometriosis and tubal surgery, previous ectopic pregnancy, and ovulation induction. The hormonal milieu at the moment of transfer has been proposed as possible causes as well [8]. Thus, it seems more important to limit the number of embryos transferred, particularly in patients who present risk factors for HP and in young women, thereby minimizing the risk of EP.

Concerning the prognosis of the IUP, favorable outcomes are reported in 50–60% of cases [2]. In HPs, spontaneous or induced abortions are more likely to occur than with intrauterine-only pregnancies; however, birth outcomes are similar, when an intrauterine gestation of a heterotopic pregnancy results in a live birth [9].

Management of HP should be conservative if possible; the primary goal is removal of the EP, while preserving the intrauterine pregnancy. Several treatment modalities have been described, either surgical or medical. The choice of treatment depends mainly on the hemodynamic condition of the patient, localization of the ectopic pregnancy, and desire for the ongoing pregnancy and future pregnancies.

The safety of laparoscopy during pregnancy has been well documented [1]. The advantages of laparoscopy compared with laparotomy in postoperative recovery are well known [1]. Laparoscopy allows prompt diagnosis and treatment, thereby providing good outcome avoiding the postoperative inconvenience of laparotomy, and has the advantage of an immediate result compared with medical treatment. In our case, the pregnancy was not affected by the operation and resulted with delivery of healthy twins.

Moreover, every physician dealing with ART should be aware of the possibility of HP, even in the absence of any predisposing risk factors. A high index of suspicion followed by an early surgical laparoscopic intervention can minimize maternal morbidity and preserve continuing IUP.


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Wednesday 20 November 2019

The hysteroscopic view of infertility: the mid-secretory endometrium and treatment success towards pregnancy

Abstract

The purpose of this study was the analysis of a correlation, in infertile patients, between the quality of the endometrium based on its vascularisation and the chances of conception. Hysteroscopy was carried out to determine the quality of the endometrial surface using the Sakumoto–Masamoto classification (“good” vs. “poor” endometrium) in the secretory phase of the menstrual cycle. The results were set in relation to the outcome of the subsequent infertility treatment, i.e. the establishment of a pregnancy within the study period (4 years). In 108 (67%) of the 162 followed-up patients, the endometrium was endoscopically classified as “good”, while in 54 (33%) the result was “poor”. The overall pregnancy rate was 37% (60 patients); 47 of all pregnancies (78%) occurred in women with a “good” endometrium while 13 (22%) had a “poor” classification. This positive association between the establishment of a pregnancy in the follow-up and a "good" classification of the endometrial vasculature in the group with a "good" endometrium was significant (P = 0.0165, Fisher's exact test). This study confirms the usefulness of endometrial evaluation by hysteroscopy as a diagnostic instrument for providing a prognosis of the chance for the patients to become pregnant.

Background

One of the most difficult questions put forward by patients after the failure of a fertility therapy such as in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) is related to the lack of success. The implantation rate per transferred embryo normally does not exceed 30%. Often the failure of “embryo implantation” is given as an explanation as the failure in one of the most critical stages at the beginning of conception, i.e. when apposition and implantation has to occur inside the uterine cavity. Current knowledge about the mechanism of these interactions is still difficult to interpret [1].

Various different suggestions have been made for investigating these mechanisms and attempting to understand which would be the characteristic elements of the endometrium that ensure ideal conditions for the embryo; but they have until today been limited to the so-called theory of the endometrial “opportunity window” [2] and did not offer effective clinical instruments for understanding which groups of patients would be at an increased risk of embryo implantation failure [3]. By using hysteroscopy as a diagnostic procedure for the assessment of pathologies inside the uterine cavity, it has, however, been shown that the differential characterisation of the endometrial surface could be a helpful tool for evaluating the in vivo vascularisation of the uterine mucosa. Already, Sakumoto et al. in 1992 in the first place [4], and after him Masamoto et al. in 2000 [5], have described the technique and used this differentiation in order to demonstrate that the endometrium could be classified into two distinct groups: a “good” endometrium, which has circular gland openings and an intense vascular ramification on one hand, and a “poor” endometrium, which is characterised by a surface with a lower gland and vascular density on the other.

The purpose of this study was to demonstrate the impact of the hysteroscopy, according to this vascularisation-based staging, and to investigate whether this endometrium quality could be used as a tool to assess the potential to achieve a pregnancy irrespective of the chosen type of infertility treatment.

Materials and methods

All infertile patients attending our fertility centre and with a regular menstrual cycle were asked to participate in this comparative, prospective study. They underwent a pre-operative transvaginal sonography (TVS), a full hormonal assessment (FSH, LH, 17β-estradiol, thyroid-stimulating hormone and prolactin) in the serum on cycle days 3 to 5 and then a hysteroscopy in the second part of the menstrual cycle for evaluating the vascularisation of the endometrium. Informed, written consent was obtained from the patients after explanation of the study by the clinician prior to the procedure, and they were asked to avoid a pregnancy in the examination cycle. The study protocol was approved by the local ethical committee.

The inclusion criteria were infertility (absence of conception after 12 months of regular, unprotected intercourse), age less than 43 years, regular cycles (25–31 days) and normal hormonal values (including FSH <12 mU/mL) had to be fulfilled. All partners provided a spermiogram for the exclusion of male factor infertility. Further exclusion criteria were known causes of uterine malformations, endometrial adhesions and hormonal therapy such as oral contraceptives or other oestrogen–progesterone medications within the last 3 months before hysteroscopy. If necessary, the procedure was combined with a laparoscopy to test the tubal patency, and the hysteroscopy was done in most cases during the same operating session and under general anaesthesia. The ultrasonographers were located in the same university department, but not involved in the surgical procedure, and the surgeon was blinded to the TVS findings.

The endometrial surface was evaluated according to the Sakumoto–Masamoto grading ("good" vs. "poor"). Endoscopic findings were categorised as "good" with an appearance representing ring-type glandular openings and maximal glandular secretion or "poor" with a low development level of vessel networks on the endometrial surface. This is illustrated in Fig.1. Hysteroscopic procedures were carried out when indicated (e.g. polyps, myomas, adhesions, septa). The diagnostic hysteroscopy was performed with a 5-mm-outer diameter scope (30°, Karl Storz) connected to a standard endoscopic camera, and a saline solution at low pressure (not higher than 60 mmHg) was used for the distension of the uterine cavity. Hysteroscopic findings were observed and analysed by three gynaecologists using videotape records.

The follow-up interval lasted for 12 months from hysteroscopy. Data were recorded and analysed for a correlation between the vascularisation score of the endometrium and the occurrence of embryo implantation (spontaneous pregnancy, successful outcome after hormonal stimulation with or without intrauterine insemination or successful IVF/ICSI-embryo transfer treatment). For statistical evaluation, the Fisher's exact test was applied using GraphPad Prism Software (San Diego, USA). For alpha, we considered 0.05 as cutoff value to avoid type I error.


Findings

A total of 178 infertile women underwent a hysteroscopic assessment, and 162 (91%) of them could be followed up in our hospital. A "good" endometrium according to Sakumoto–Masamoto staging was diagnosed in 108 of them (67%), while 54 (33%) patients were graded as "poor". No differences in the distribution pattern of the causes and duration of infertility, the age of the patients (mean 33.8 years in the "good" and 33.6 in the "poor" group) or the pre-treatment day 3 serum level of follicle-stimulating hormone (6.8 and 7.4 U/L) were observed between these two groups.

A normal uterine cavity was reported in 133 (83%) women, while endometrial polyps, submucosal fibroids, adhesions or uterine malformations were found in 29 cases (17%). On the other hand, the pre-operative TVS indicated intrauterine pathologies in 15 cases (9.3%). The overall pregnancy rate was 37% (60 women); 15 women became pregnant spontaneously, 22 patients succeeded after follicular stimulation with recombinant gonadotropins (rFSH) and 23 after treatment with in vitro fertilisation and embryo transfer including ICSI.

In the total pregnancy group (N = 60), a "good" endometrium was found in 47 women (78%) while this was the case in 61 patients (60%) of the group who did not achieve a pregnancy. Forty-one patients with a "poor" endometrium did not succeed in getting pregnant. Only 13 patients with a “poor” endometrium did succeed in establishing pregnancy in the follow-up. The association between endometrium quality by Sakumoto–Masamoto classification and pregnancy outcome was statistically significant (P = 0.0165, OR = 2.43, CI = 1.17–5.05); the contingency matrix for the pregnancy outcome is shown in Table 1.


Conclusion

Our results confirm those of the studies carried out by Sakumoto and Masamoto [4, 5], indicating that a hysteroscopic examination of the mid-secretory endometrium can be a reliable instrument for determining the chances of a patient to become pregnant. The classification in “good” and “poor” is leading to the conclusion that a poorly vascularised endometrium with limited glandular (secretory) structures may result in a tissue which is not suitable for a correct embryo implantation and endometrial development, and this irrespective of other factors of sterility.

Nevertheless, our results showed a lower fraction of patients (one third) with a “poor” endometrium in comparison to earlier studies (45.9% in the study of Sakumoto [4] and 61.3% in Masamoto et al. [5]): we believe that this difference can be explained with a different patient selection in the study groups. As a matter of fact, we did not focus on patients with a history of repeated abortions as it was the case in the study of Masamoto [5], but on a global infertile population.

Another clearly interesting but only partially surprising finding is the high percentage (17.2%) of intrauterine pathologies that have been diagnosed in the hysteroscopic examination when compared to the total number of patients with suspected intracavitary problems found in the pre-operative sonography (9.3% of all women, and this in spite of all ultrasound examinations having been carried out by the same team of experienced gynaecologists). These results, nevertheless, are in large agreement with previously published studies [6, 7].

We therefore conclude that a hysteroscopic examination, particularly in cases of idiopathic infertility or after several unsuccessful treatment cycles with in vitro fertilisation [8], is strongly indicated [9] and has the added benefit of providing a prognostic measure for determining the chances of the patient to become pregnant, in the future, in addition to its diagnostic significance [10].



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Thursday 14 November 2019

Transvaginal access: a safe technique for tubo-ovarian exploration in infertility? Review of the literature

Abstract

Transvaginal laparoscopy offers an accurate and minimally invasive method for the exploration of the female pelvis in patients with infertility. Access to the pouch of Douglas is gained through a simple needle puncture technique of the posterior fornix using a pre-warmed watery solution as the distension medium. A review of recently published papers and our own experience illustrate the safety of the technique. Transvaginal laparoscopy can be considered as one of the first and safest examples of the recent developments in natural orifice transluminal endoscopic surgery (NOTES).

Introduction

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Transvaginal laparoscopy is today accepted as a feasible technique for the investigation of female fertility with the capacity to predict spontaneous ongoing pregnancy comparable to that of laparoscopy. The technique uses saline as the distension medium and is generally performed in an outpatient setting under intravenous sedation or local anesthesia [1, 2].

Transvaginal access has previously been used in culdoscopy, as introduced by Decker and Cherry [3] in the US and Palmer in Europe [4], but was abandoned in the 1970s, particularly when studies suggested that the transabdominal access was superior over transvaginal access for the performance of tubal sterilization [5, 6]. Recently, the Editorial Board of the American Association of Gynecologic Laparoscopists [7] expressed the fear that, after transvaginal access, 1% of infertility patients would develop peritonitis and pelvic abscess. The fear was based on the statement that vaginal tubal sterilization carried with it a 1% abscess rate when performed in an operating room, even with the administration of prophylactic antibiotics. It is questionable on which data this statement has been based and whether it is supported by old and recent data.

Palmer [4] admitted that, after posterior colpotomy, pelvic abscesses are possible and 2% of the sterilizations fail because of fistulization of the ampulla. Whitaker [8] reviewed a series of 585 tubal ligations by colpotomy within a private-practice setting in the US. In his series, no vaginal cuff hematoma and cuff abscess requiring incision and drainage occurred. Gupta et al. [9] analyzed a series of 608 women admitted to the Department of Obstetrics and Gynecology in Chandigarth, India. No prophylactic antibiotics were given and follow-ups occurred at regular intervals up to 12 months. Two cases of serious complications, including one abscess with fistula and one pelvic peritonitis, occurred. In a review of 50,151 laparoscopies, Brosens et al. [10] reported that diagnostic laparoscopy was associated with a 0.08% risk of bowel injury. However, up to 15% of the injuries are not diagnosed during laparoscopy and one of five cases of delayed diagnosis resulted in death [11–13].

In a multinational retrospective survey in 2001, we reported on a series of 3,667 procedures of transvaginal pelvic endoscopies in infertile patients without obvious pelvic pathology [14]. Full-thickness bowel injury occurred in 24 (0.65%) procedures. After an initial experience of 50 procedures, the prevalence of bowel injury was 0.25%. However, all injuries were diagnosed during the procedure and 22 (92%) were managed conservatively without consequences. Both the type of lesion and the risk of delayed diagnosis suggest that the transvaginal access in laparoscopy is associated with a minor risk of bowel injury that, under strict conditions, is treated conservatively. The purpose of this review is to evaluate the risk of bowel injury during transvaginal laparoscopy in recent publications.

Survey design

Using the Pubmed and Scopus searches, we traced 27 original papers on diagnostic transvaginal pelvic endoscopy published between 2000 and 2007 in peer-reviewed journals. We excluded recent publications from the pioneering centers to exclude overlapping data and to include results from new centers with their initial experience. With regard to publications in languages such as Japanese and Polish, data were collected from the available English abstract.

Instrumentation

Transvaginal laparoscopy is performed using a combined system of a Veress needle and trocar with a 3.9-mm outside diameter and a semi-rigid endoscope of 2.7 or 2.9 mm, as developed by Karl Storz GmbH & Co., Tuttlingen, Germany [15–20]. Fertiloscopy is defined as the combination in one investigation of transvaginal hydropelviscopy, dye test, optional salpingoscopy, and hysteroscopy [21]. The slightly different instrumentation as developed by Soprane S.A., Lyon, France, has an outer diameter of 6 mm.

Complications

The 27 publications on transvaginal laparoscopy and fertiloscopy represented a total of 2,843 procedures (Table 1). Access was achieved according to 11 publications, each reporting on more than 50 procedures between 89% and 100%, with a mean of 94%. Access failed in 6% of the cases and the reasons included retroverted uterus, dense adhesions, adnexal mass in the cul-de-sac, nodular retrocervical endometriosis, and obesity.


No major complication, such as life-threatening hemorrhage, bowel injury requiring surgery, sepsis, or abscess formation, occurred. Minor complications occurred in 21 (0.74%) patients (Table 2). These complications included bowel injury in 10 cases (0.35%). All were treated conservatively with antibiotics. Hemorrhage requiring compression or a stitch was reported in six cases, inadvertent puncture of the posterior uterine wall in three cases, and suspected pelvic infection treated with antibiotics in two cases. No long-term or delayed complications were reported.

Prevention of complications

Previous research has shown that, after initial experience with 50 procedures, the risk of bowel injury decreases significantly. The findings of our previous survey [14] clearly demonstrated a decrease in incidence in bowel damage from 1.3% in the first 50 cases to 0.25% once more experience had been gained. Also, in their series, Verhoeven et al. [48] reported a reduced incidence of 0.1% once more than 50 procedures have been performed. However, even in experienced hands, injury during blind access cannot be fully avoided. Sobek et al. [23] recommended ultrasonographically guided transvaginal hydrolaparoscopy to increase the safety of the procedure and decrease the difficulty of access. With this method, no bowel injury occurred in a consecutive series of 460 patients. Mgaloblishvili et al. [22] proposed to proceed first with hysteroscopy using saline for partial filling of the pouch of Douglas, followed by sonohysterosalpingography to clearly visualize and assess the fornix and the pouch of Douglas. Cancellation for transvaginal pelvic endoscopy included:

  • Complete obliteration of the pouch of Douglas
  • Thickening of the posterior fornix by dilated vessels, retro-cervical endometriosis, or adipose tissue
  • Dense adhesions in the pouch of Douglas
  • Presence of organs such as one or both ovaries, fallopian tubes, intestinal loops, myomatous nodule, or retroverted uterus
  • Bilateral hydrosalpinges

In a series of 827 women, cancellation was indicated in six cases after hysteroscopy and in 135 cases after sonohysterosalpingography. No complications occurred in the remaining 702 patients.

Comments

The current findings support the conclusion of the previous report by Gordts et al. [14] that transvaginal access using a small-diameter endoscope for the exploration of the pelvis in infertility is a safe procedure. In contrast with transabdominal access in standard laparoscopy, delayed diagnosis of bowel injury resulting in sepsis or death has not been described. Moreover, bowel injury caused by the small-diameter instrument used in transvaginal pelvic endoscopy can be treated expectantly, although antibiotics are administered in most cases. This, however, will not exclude that inadvertent manipulation may cause a large lesion that requires surgical repair. In the absence of leakage, expectant management with the prophylactic use of antibiotics is apparently justified.

It is unclear as to which literature the statement by Hunt et al. [7] that culdoscopic access is associated with a 1% risk of sepsis has been based. Review of the early literature learns that the current findings on the risks of transvaginal access in women with infertility are in full agreement with the older literature on the risks of diagnostic culdoscopy. Riva et al. [49] published a consecutive series of 2,850 cases with 3.7% failure of access and a complication rate of 1.4%. Eleven recto-sigmoid perforations occurred (Table 3). The lesions were extra-peritoneal and were closed immediately through the colpotomy site, and the culdoscopy procedure was discontinued. Follow-up examination revealed no complications referable to these recto-sigmoid injuries. Diamond [50] used improved instrumentation and brighter illumination with fiber optics and published in 1978 a continuous series of 4,000 outpatient procedures of diagnostic culdoscopy in infertility. In his consecutive series of 4,000 culdoscopies performed between 1968 and 1978, no death occurred. Bleeding was prolonged and required suturing in six patients. Pelvic infection occurred in three cases, despite the routine use of antibiotics, and one patient developed a pelvic abscess. Inadvertent punctures were made into the rectum in five cases, all of them occurring in the first five years of the series and none later. None of the patients required hospitalization or laparotomy; all were treated with antibiotics and conservative therapy. No inadvertent puncture of other viscera occurred. In four patients, the puncture of ovarian cysts that had prolapsed into the cul-de-sac occurred. Diamond [50] concluded that, with proper preparation and organization, diagnostic culdoscopy could be carried out as a routine procedure in any adequately equipped outpatient facility in or outside the hospital. It is safe, effective, and rapid, taking an experienced physician and team no more than 10 or 15 min to perform. He proposed that outpatient culdoscopy should be returned to gynecologic training programs. With regard to the available data in the literature, the statement of the Editorial Board of the American Association of Gynecologic Laparoscopists is, therefore, astonishing. We would agree with Hunt et al. [7] that a thousand, or even several thousand, cases are required to make a statement on the safety of a new technique. The world literature during the last 40 years includes many thousands of procedures and has consistently endorsed the safety of transvaginal access in diagnostic pelvic endoscopy in women with infertility.


In infertility exploration, transvaginal laparoscopy is one of the first applications of the recent developments in natural orifice transluminal endoscopic surgery (NOTES) [51]. Considering the previously discussed results, the technique should deserve a more widespread use as an ambulatory diagnostic tool in the exploration of the infertile patient.


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Friday 8 November 2019

Role of transvaginal hydrolaparoscopy in the investigation of female infertility: a review of 1,000 procedures

Abstract

Transvaginal hydrolaparoscopy is a culdoscopic approach for the inspection of the posterior pelvis, but, in contrast to culdoscopy, uses an aqueous solution for the distension of the pelvic cavity and small diameter optics. The technique is used for diagnostic purposes in patients with infertility and is performed under local anesthesia or conscious sedation in an ambulatory surgical center. We report on a continuous series of 1,000 patients with infertility and without obvious pelvic pathology. Access and good visualization was obtained in 96.8% of the patients. The main complications were intraperitoneal bleeding and bowel perforation, which after the initial period occurred respectively in 1.9 and 0.1%. All complications were managed conservatively, and no major complication occurred. Clinically significant pathology was diagnosed in 25% of the patients, which allowed immediate triage of the patients for further management. Transvaginal hydrolaparoscopy can be proposed as a first line technique to replace hysterosalpingography and diagnostic laparoscopy in the exploration of patients with unexplained infertility.

Introduction

In Europe over the past 40 years, endoscopic evaluation of the pelvis has become an integral part of the infertility work-up. In routine practice, hysterosalpingography (HSG) is the first-line investigation and, if normal, laparoscopy is frequently delayed for 6 months or more. Laparoscopy is indeed an invasive procedure, associated with potentially serious complications, and together with hospitalization it can also be an expensive procedure. On the other hand, HSG is inferior to the chromopertubation test for the diagnosis of tubal patency [1] and also has a low sensitivity for the diagnosis of pelvic endometriosis and adhesions. If laparoscopy is performed as a first-line investigation on all infertile patients, there will be a large number of patients with normal findings or with minor pathology that has no or doubtful impact on the management of infertility.

It has been argued that with the advent of ART, laparoscopy can be omitted from the infertility work-up when there is no abnormal contributing history and the HSG is normal and, as a consequence, the cost of fertility treatment is reduced without compromising success rates [2]. Karande et al. [3], however, found in a prospective randomized trial that a higher pregnancy rate with lower costs is achieved with a traditional treatment algorithm than with IVF-embryo transfer as a first line-therapy.

We therefore wish to report on a continuous personal (H.V.) series of 1,000 procedures of transvaginal laparoscopy (THL), which were performed in combination with the mini-hysteroscopy and chromopertubation test as a first-line investigation of female infertility [4]. The combination of the three procedures has been coined transvaginal endoscopy (TVE).

Materials and methods

THL was discussed with all women who met prospectively established exclusion and inclusion criteria. In all patients, the indication was primary or secondary infertility. The patients had a complete history, physical examination and transvaginal sonography. Patients were excluded if they had an indication for operative laparoscopy, abnormal pelvic findings such as fixed retroverted uterus, rectovaginal endometriosis, large ovarian cyst or obliterated cul-de-sac, or an upper vaginal stenosis. Patients with vaginal or pelvic infection were first treated before THL was performed.

THL was used as described by Gordts et al. [5]. With the patient in the dorsal decubitus position, only a limited amount of fluid is required to have the tubo-ovarian structures floating in the excavation of the posterior pelvis. We used a narrow-diameter (<3.5 mm), foroblique 30°, wide-angled and rigid optic, a high intensity light source and a digital camera. Inspection of the pelvic structures was achieved without grasping or manipulation. At the end of the procedure a chromopertubation test was performed and, when indicated, salpingoscopy was added. All interventions were performed under conscious sedation as an office procedure in an outpatient surgical suite.

Transvaginal laparoscopy was considered complete if the tubo-ovarian structures, pelvic sidewalls and cul-de-sac could be seen, or if pathology was diagnosed that indicated the need for operative intervention or ART.

Results

A total of 1,000 THLs were performed during the period starting from 1998 until 2003. Thirty-two (3.2%) failures occurred with failed access in 11 (1.1%) and absent or poor visualization in 21 (2.1%). In total, 968 (96.8%) of the procedures were completed. No pathology or pathology of minor clinical significance was found in 736 (76%). In the group with completed procedures, unexpected clinically significant pathology was diagnosed in 240 (25%) and included mainly ovarian endometriosis, tubo-ovarian adhesions, isthmic block and hydrosalpinges. The diagnostic findings resulted in 36 (3.7%) operative laparoscopies and 204 (21.1%) medical therapies and ARTs.

No major complication occurred in this series. Intraperitoneal bleeding was seen in 23 (2.3%) of the patients and occurred on the posterior wall of the uterus (n=13), parametrium (n=2), ovary (n=2), omentum (n=1) and adhesions (n=5). Bowel perforation occurred in 5 (0.5%) and was managed conservatively with antibiotics. Infection occurred in two (0.2%).

The correlation of the failures (no access or no visualization) with the experience showed that 5 (10%) failures occurred in the first 50 procedures and 26 (2.8%) in the subsequent 950 procedures (P=0.018). Bleeding occurred in 5 (10%) of the first 50 cases and 18 (1.9%) of the following 950 cases (P=0.004). Bowel perforation occurred in 4 (8%) of the first 50 cases and in 1 (0.1%) of the following 950 cases (P<0.0001).

Discussion

By using TVE as a first-line investigation of female infertility, we avoided HSG in 96.8% and laparoscopy in 93.2% of the patients. In 24% of the patients, unexpected major pathology was diagnosed and recommendations for operative laparoscopy, medical therapy or ART could be made.

Several studies have validated the feasibility, reproducibility, diagnostic accuracy, acceptability and safety of the procedure [6]. Different centres have reported access in over 95% and normal findings in 41 to 59% of the cases. In this series of 1,000 consecutive cases, access and visualization of the pelvic structures were achieved in 96.8% of the patients. The performance of THL is defined by visualization of the ovaries, fallopian tubes, posterior wall of the uterus, ovarian and uterosacral ligaments, sidewall of the posterior pelvis and cul-de-sac. In this series, these structures were normal or showed pathology of minor significance in 76% of the patients.

The potentially serious complication of transvaginal access is rectal perforation and sepsis. In a survey of 3,667 procedures the incidence of bowel perforation was 0.65%, which decreased after the initial experience to 0.25%. No delayed diagnosis and sepsis occurred, and 92% of the cases were managed with outpatient antibiotics [7]. In the present series minor bleeding occurred in 2.5% and bowel perforation in 0.5% of the patients. Analysis of the occurrence of complications in function of experience confirmed the importance of the learning curve. After the initial 50 cases, the complication rate of intraperitoneal bleeding and bowel perforation decreased significantly to 1.9 and 0.1%, respectively. It should, however, be noted that even in experienced hands these complications can occur and, therefore, the patients need to be informed. However, in this series no major complication such as sepsis occurred and, similar to previous series, most bowel perforations were managed conservatively with antibiotics without consequences.

As a first-line procedure for the investigation of female infertility, TVE is in direct competition with HSG. The prognostic value of the chromopertubation test has been shown to be better than that of HSG [1]. Four authors reported abnormal findings at THL in 44% of 241 patients with normal or suspected hysterosalpingography [6]. Shibahara et al. [8] compared HSG versus THL in a series of patients with and without a history of Chlamydia infection and found that THL was superior for the diagnosis of peritubal adhesions. The additional advantage of THL for tubal exploration is the ability to examine directly the tubal mucosa by salpingoscopy. Salpingoscopy is a better predictor for pregnancy outcome after tubal reconstructive surgery than routine investigation by HSG and standard laparoscopy [9, 10].

Fatum et al. [2] suggested that in patients with a normal HSG, laparoscopy would be superfluous and patients should undergo up to six cycles of gonadotropins and IUI and then undergo IVF if they continue to be infertile. However, in a recent study Capelo et al. [11] found significant pelvic pathology in one third of the patients failing to conceive after four ovulatory cycles of clomiphene citrate and concluded that early endoscopic diagnosis of such pathology would have allowed the couple to proceed directly to IVF.

Cicinelli et al. [12] found in a randomized controlled trial that THL in combination with mini-hysteroscopy in an outpatient setting was better tolerated by the patients than HSG. Finally, HSG is a diagnostic X-ray procedure that exposes the bladder, ovary and colon to radiation. The organ-specific radiation doses of HSG for the bladder and colon are estimated at 4.67 and 2.82 mGy, respectively. It is now generally accepted that there is no threshold dose below which radiation exposure does not cause cancer, and the attributable risk of diagnostic X-rays is estimated to range from 0.6 to 1.8 of cases of cancers per year [13].

When an accurate infertility exploration can be performed with a minimally invasive procedure and a reliable treatment exists, an early diagnosis followed by the most appropriate, effective treatment can greatly reduce the monthly failures and the sense of frustration for the couple, particularly when age and time are additional unfavorable factors.

Our current approach of exploring female fertility after 1 year or more of infertility may paradoxically lead to undertreatment as well as overtreatment.

Recent prospective population-based studies have demonstrated that the time to clinical pregnancy in most women with normal fertility is not more than 6 months [14, 15]. It can therefore be assumed that already after six cycles with fertility-focused intercourse, irrespective of their age, most women with normal fertility have conceived and that the remaining group is largely composed of couples faced with subfertility. Today, when female fertility can be explored accurately with a minimally invasive procedure, such as TVE [4], and a reliable treatment exists for many major disorders, a prolonged waiting period is outdated [16].


It is concluded that in women with previously normal cycles infertility should be investigated already after a 6-month period of fertility-focused intercourse and that transvaginal endoscopy, which combines minihysteroscopy and transvaginal hydrolaparoscopy, can be proposed as a first-line technique.



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Wednesday 6 November 2019

Lithopedion diagnosed during infertility workup: a case report

Introduction

Lithopedion is an exceedingly rare entity in the modern era of medicine. Since the earliest case discovered in 1582 in France (Bondeson 1996), less than 300 cases of lithopedion have been reported (Irick et al. 1970; Frayer and Hibbert 1999; Spiritos et al. 1987). However in places with limited access to health care facilities and poor health awareness, lithopedion on rare occasions can baffle physicians with its appearance. Here we report a case of lithopedion in a young woman of 20 years resulting from ruptured ectopic pregnancy who attended our hospital for infertility.


Case report

A 20 years old lady married for 2 years came with complaints of inability to conceive. Her menstrual cycles were regular except for a single missed cycle which occurred about 18 months back. She did not visit any doctor for confirmation of pregnancy. She resumed her menstruation thereafter and continued to have it till date. She however had occasional pain abdomen which was relieved by analgesics she purchased over the counter. Physical examination revealed a lump in the right lumber region hard in consistency with restricted mobility and tender on movement. Laboratory workup revealed no abnormal values. X-ray of abdomen and pelvis in erect posture revealed radio-opaque shadow resembling foetal skeleton in right lumber region (Figure 1). Ultrasound examination confirmed intraperitoneal dead, calcified foetus of approximately 17 weeks gestational age along with an echogenic mass in left adnexa.



With these findings, a provisional diagnosis of lithopedion was made and laparotomy was planned. A hard globular mass adherent to the omentum was found in the right flank. The mass was dissected off the omental tissue and a calcified foetal skeleton was recovered (Figure 2). Fallopian tube on the left side in the isthmic region contained a rent with a calcified growth that filled the tube causing a localized distension (Figure 3). This was confirmed to be calcification of degenerated chorionic tissue by histopathology with no evidence of inflammation. Left sided salphingectomy was done. Contralateral tube and bilateral ovaries were normal. Pouch of douglas was free of adhesion. Postoperative recovery was uneventful and patient was discharged on 7th postoperative day. Only 4 months after the surgical procedure, the patient again visited our OPD with complaints of cessation of menstruation for 2 months. Intrauterine gestation was confirmed. Patient attended antenatal clinic regularly. She subsequently delivered at 38 weeks a healthy female baby weighing 2.8 kg spontaneously.


Discussion

Lithopedion is a greek word which means ‘stonechild’. This rare event occurs in 0.0054% of all gestations (Ede et al. 2011). Incidence of secondary abdominal pregnancy is 1 in 11,000 pregnancies. Lithopedion occurs in 1.5 to 1.8% of these cases (Costa et al. 1991; Frayer and Hibbert 1999).

Lithopedion describes an intraabdominal calcified dead fetus. A lithopedion can result from a primary abdominal pregnancy, or from a secondary abdominal implantation following tubal abortion or rupture of tubal or intrauterine pregnancy. It occurs when a sterile extrauterine fetus survives for more than 3 months in abdominal cavity and escapes medical discovery along with minimal and sluggish circulation inviting calcium deposition (Irick et al. 1970; Frayer and Hibbert 1999; Costa et al. 1991). Secondary abdominal implantation is one of rarest consequence of ruptured tubal pregnancy and the formation of lithopedion out of it is even rarer.

Age of the patients in various case reports ranged from 23 to 100 years at the time of diagnosis (Lachman et al. 2001). The occurrence of this rare condition in a woman of 20 years in our case is quite unusual. Preoperative diagnosis of lithopedion was made with simple diagnostic tools averting the need for expensive, sophisticated gadgets. This is specially rewarding in areas with scarce diagnostic facilities where from these rare cases of lithopedion are reported. The formation and diagnosis of lithopedion in our case (Figure 4) occured in less than 18 months duration since the gestational age of the recovered stonechild far exceeds an estimated period of 8 weeks when the tubal rupture is assumed to occur. This therefore is the earliest period of diagnosis in literature with various case reports citing the period of retention to be 4 to 60 years (Ede et al. 2011). The tubal rupture which resulted in secondary abdominal pregnancy is evident from the rent in the tube that was filled with calcified growth of degenerated chorionic tissue. This synchronous evidence of cause and effect is unique in itself rendering this the first of its kind. In view of the absence of salphingitis or adhesion, the obvious cause of ectopic pregnancy could not be elicited. However factors causing infertility could probably be imputed to lithopedion on the right side resulting in distorsion of pelvic anatomy hindering ovum pickup. Removal of lithopedion restored the tubo-ovarian relationship resulting in conception within 2 months of surgical intervention. Salphingectomy was adopted as the procedure of choice as the tube was grossly damaged. Surgical intervention is hence well justified in this young lady in contrast to conservative approach in view of the long survival years that can ensue her to various complications.


A rare entity though, lithopedion is not exinct and its diagnosis should not be missed in young infertile patients where period of retention may be small with minimal symptoms and vague obstetrical history. Appropriate history and keen suspicion in such cases from areas with limited access to healthcare facilities not only helps in diagnosis but can avert the dreadful complications it can accrue in course of time.


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Saturday 2 November 2019

Transvaginal endoscopy: new technique evaluating female infertility. Three Mediterranean countries’ experiences

Introduction

Transvaginal endoscopy (TVE) has recently been introduced as a useful method for the diagnosis of infertility in women [1]. By insertion of a 3.5 mm-diameter telescope through the posterior vaginal fornix, the fallopian tubes and the adnexae can easily be visualised and further investigated [2]. This method has been proposed for infertile women with low risk of pelvic abnormality, a rather normal gynecological history and normal sonographic appearance of the pelvis.

The traditional investigation of an infertile woman without suspicious history of pelvic adhesions or endometriosis is by hysterosalpingography (HSG). In patients with normal HSG results, induction of ovulation and artificial insemination with the husband’s sperm is usually proposed for 4–6 cycles. If no pregnancy is achieved, then laparoscopy and hysteroscopy follow. The development of small-diameter telescopes has promoted pain-free hysteroscopy as an office procedure and recommended its application in every infertile woman prior to any infertility treatment [3].

The application of TVE as a substitute for standard diagnostic laparoscopy has encouraged gynaecologists to consider changes in their recommendations for infertile women with no obvious pelvic abnormalities [4]. By the application of office hysteroscopy and TVE, the mechanical factor within the uterine cavity, the ostia, and the proximal and distal part of the tubes can be eliminated, and no infertility treatments are given without complete diagnosis [5].

TVE can verify pelvic micro- and filmy adhesions and foci of endometriosis, which are not visible with standard laparoscopy [6]. Also, the small-diameter telescope can be inserted within the fibria (fibrioscopy) and propagated to the endosalpinx (infundibulum), enabling evaluation of the distal part of the salpinx. The diagnostic advantages of TVE over traditional laparoscopy, and which patients have an indication for TVE, are still under evaluation, and more studies are needed to draw final conclusions [4].

The aim of our study was to evaluate and compare the performance, diagnostic potential and the results of TVE at the initial learning period of five gynaecology groups in three different countries.

Patients and methods

Patients

We performed TVE between 1 January 1999 and 13 July 2001 on 78 infertile patients. Their average age was 33 (32–34)  years, and the mean number of years of their infertility problem was 3.7 (3–5) years. We recruited three groups of patients. Group A comprised 46 patients that were operated on in Milan and Bologna, in Italy. Group B contained ten patients in Ioannina, Greece, and group C was composed of 22 patients in Nicosia, Cyprus. All patients were selected to be at minimal risk of pelvic adhesions, and vaginal sonography verified uterus and ovaries to be normal. The first four patients of each group were examined by laparoscopy, to evaluate the potential of the technique and minimise risks for the patients.

Method

The procedure of TVE was followed as published by Gordts et al. [7]. In the operating room the patients were placed in the lithotomy position, and a drip infusion was administrated. Heavy sedation was used as anaesthesia. After the patient had undergone disinfection with aqueous chlorhexidine solution, hysteroscopy was performed. A metallic cannula was then adjusted to the cervical os for the use of chromotubation. The cervix was lifted with a tenaculum placed on the posterior lip, and, in some cases, the central part of the posterior vaginal fornix was infiltrated with 2 ml of 1% lidocaine. The Veress needle was introduced 1.5 cm below the cervix and inserted into the pelvic cavity. Approximately 200 ml of warm saline solution was introduced into the pouch of Douglas. A 3 mm blunt trocar was inserted by a stab incision in the posterior fornix; then, a 2.7 mm-diameter rigid endoscope was used, with an optical angle of 30°, attached to a video-camera. The saline irrigation continued throughout the procedure to keep the bowel and tubo-ovarian structures afloat. The posterior of the uterus and the tubo-ovarian structures were carefully observed, and tubal passage, using indigo-carmine, was confirmed. In some cases the infundibulum of the endosalpinx could be visualised.

Results

All 78 patients tolerated TVE very well, and no cancellations were reported. The average time of the whole procedure was 30 min. Hospitalisation days varied, being 4 h for group C, 48 h for group A and 24 h for group B. No long-term postoperative complications or infections were reported. Trocar entry complications, pain and bleeding were reported in one patient in group C and two in group B, which stopped after pressure. Postoperative bleeding was reported in one patient in group B, which stopped after the port entry in the vaginal vault had been sutured. One patient in group B had a bowel perforation, which was diagnosed early and treated conservatively with antibiotics.

The visualisation of the tubo-ovarian structures was reported in all cases in group A, in 7/10 (70%) cases in group B and in 17/22 (77%) cases in group C. The TVE findings are shown in Table 1 and differed in each department. In 30–50% of the cases normal pelvic findings were reported. The rate of pelvic endometriosis diagnosed ranged from 9% to 20%, and the overall frequency of adhesions was 20%.

The number of CO2 laparoscopies needed to verify the diagnosis made by TVE ranged from 7% to 10%, as shown in Table 2. The overall number of patients who avoided having to have CO2 laparoscopy, by undergoing TVE, was 41/78 (51%). The remainder of the patients, 30/78 (38.5%) after the diagnosis was established by TVE, needed to undergo either further surgery for adhesiolysis or IVF treatment.

Discussion

This study presents the initial application and the results of the new method of TVE in three countries. All units demonstrated similar high diagnostic potential and minimal complication rates in the TVE procedure and wide acceptability of the method by the patients. The fact that patients underwent this procedure under heavy sedation, and that the average time of inspection was half an hour, minimised hospital stay and increased acceptability by the patients for the proposed TVE procedure. The time of hospitalisation after TVE varied enormously among the three groups and was decided in advance by every department separately, depending on their protocol rather than on the real need of patients’ hospitalisation. Since TVE is a new method, the safety of the method should be secured.

The observation of micro- and filmy adhesions and foci of endometriosis seen by TVE and otherwise missed by CO2 laparoscopy makes its application attractive [8]. In patients aged close to 40 years and under pressure to achieve a pregnancy as soon as possible, it seems reasonable to reassure the woman about the fertility potential prior to her undergoing any trials with ovulation induction by ruling out the 20% chance that she might have a mechanical problem. The simplicity, safety and accuracy of the results of TVE encourage the routine application of this method in infertile women [9].

Bowel injury is one of the risks encountered when the Veress needle and then the trocar are inserted into the vaginal vault [10]. Usually, the diagnosis of wrong entry is immediate, and conservative management with antibiotics is, in most cases, enough. Usually, these injuries are very rare and are avoided by the careful selection of patients and by experience.

Transvaginal endoscopy also has its limitations, as it is not possible for the gynaecologist to inspect the anterior part of the uterus, or the anterior pelvic peritoneum [4]. Nor is it possible for the abdominal cavity to be investigated in the way CO2laparoscopy does. However, by gaining experience, the gynaecologist can clearly recognise the appendix, omentum and even adhesions below the umbilicus. It is essential to understand that selection of patients for TVE is absolutely necessary in the first cases. Also, women suspected of having pelvic adhesions and /or needing operative laparoscopy should be excluded from TVE. The learning of the TVE technique is relatively easy, especially for gynaecologists who perform traditional laparoscopy and hysteroscopy.

When TVE and hysteroscopy methods are applied as a first choice of evaluation for all infertile woman, some hesitation arises as to whether this can be performed as an office procedure, as proposed by Gordts et al. [5] and Brosens et al. [9]. The high rate of adhesions, 20% reported in these early studies and also found by us, probably indicates the performance of TVE/hysteroscopy in the operating room, whereas operative laparoscopy can follow for patients requiring further treatment. Of course, such an option can be always discussed and settled with the patient prior to the procedure. Recent technological advances provide trocars with a working channel, and minimal surgery can be performed by TVE [11]. Further evaluation of the potential of these new instruments is necessary to exact any conclusion.

The experience of the initial steps in learning TVE in the above-mentioned units in three Mediterranean countries demonstrates that this new method of investigating female infertility is feasible, gives accurate results and is easy to learn. It is of low cost and very well accepted by the patients. The risks for perioperative complications are minimal, depending on the surgeon’s experience and selection of the patients.


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The best Infertility hospital, Care Womens Centre offers the complete range of infertility related treatments such as IVF, IUI, ICSI, test tube baby treatment and infertility treatment in Indore Madhya Pradesh. Our primary goal is to remedy a situation that prevents couples from becoming proud parents.  Book an appointment  https://www.carewomenscentre.com  and call us 8889016663.


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