Effect of Hysteroscopy Before Intra Uterine Insemination on Fertility in Infertile Couples
Uterinedisorders like usual infertility factors (male factor,
ovarian and tubal problems of women) may affect the outcome of infertility treatment
in infertile patients. In our clinical trial, 110 couples diagnosed with infertility
were candidate for Intra Uterine Insemination (IUI). The patients were divided
randomly into two equal groups (n = 55): In group one (control group), patients
without hysteroscopy underwent ovulation induction by clomiphene citrate and
hCG followed by intrauterine insemination. The second group (experiment group),
patients were undergoing hysteroscopy before intra uterine insemination on the
day 21 of the cycle and due to abnormal findings, going under surgical treatment
if they needed. The rates of pregnancy complications in patients were evaluated.
The age, BMI, kind of infertility, duration of infertility, number of previous
trial, duration of stimulation, the type of procedures used and semen analysis
(TMC, Motility and morphology of sperm) were similar for both groups and no
statistically significant differences emerged at all between them. In experimental
group, hysteroscopy revealed pathology in the uterine cavity in 26 out of 55
cases. The overall rates of clinical pregnancy were higher in experimental group
compared to the control group. The findings from this study showed that the
use of hysteroscopy as a diagnostic or therapeutic procedure before IUI, can
increase the rate of pregnancy and finally decrease the failure rate of infertility
treatment and perinatal complications in infertile couples.
Received: August 18, 2012;
Accepted: February 14, 2013;
Published: March 04, 2013
Since the implantation is most important step in the pregnancy, any uterine
anatomic abnormalities, i.e., adhesions, septa, polyps, submucous myomas, adenomyosis,
endometritis, anomalies of the cervical canal and lesions of the uterotubal
junction in the uterine can create negative influences on the fertility of female
(Merviel et al., 2000). Therefore, the appropriate
diagnosis and healing of these disorders are most essential to get well result
in restoring fertility of women. The exact examination of the uterine cavity
often is not easy by the transabdominal and the endovaginal sonography (Valenzano
et al., 2006). These methods may offer insufficient data or even
provide numerous false-positives and false-negatives on the uterine cavity (Merviel
et al., 2000).
Hysteroscopy, however, is a diagnostic procedure that makes available direct
demarcation of endometrial, submucosal, intrauterine cavity deformity and even
the cervical canal (Isaacson, 2002).
In addition, it helps avoid invasive diagnostic procedures as well as optimize
the preoperative process for the women requiring therapeutic intervention. It
is easily and rapidly carried out at an outpatient basis, without sedation,
by proper small-caliber instruments and irrigation with physiological saline
(Breitkopf et al., 2003). Furthermore, it is
well tolerated and is virtually devoid of complications (Breitkopf
et al., 2003). In addition, both hysteroscopic examination and ART
procedure can be also doing at the same time (Merviel et
al., 2000; Hucke et al., 2000). Therefore,
it seems that if the high diagnostic accuracy of hysteroscopy for intrauterine
pathologies can be a causes for the reduced fertility in women potentially,
then, it may also initiate growing consensus towards its use in the routine
investigation of infertile women prior to ART procedure (Isaacson,
2002; Hucke et al., 2000; Campo
et al., 2005), as well as in the management of hysteroscopy in place
of laparoscopy (Darwish and El-Saman, 2007; Hitkari
et al., 2007; Mijatovic et al., 2010).
The aim of this study was to assess the diagnostic value and usefulness of hystroscopy
in primary assessment before Intra Uterine Insemination (IUI) on fertility in
MATERIALS AND METHODS
This is a prospective study that carried out through the period from June 2011 to April 2012 in the Fertility, Infertility and Perinatology Research Center in Ahvaz. One hundred and ten healthy women between the ages of 22 and 44 years candidate IUI cycles were randomly assigned to one of two groups from the start of the cycle. Group 1 (experiment, n = 55) for the treatment of possible uterine disorder causes infertility underwent hysteroscopy before entering the IUI and depend on finding candidate for surgery. Group 2 (control, n = 33) took IUI without hystrscopy. It worth mentioning in group 1 if the patient had normal hysteroscopy, IUI was done at next cycle but if surgery had the IUI was done after 2 or three cycle.
The Ethics Committee of Jundishapour Ahvaz University of Medical Sciences approved this study. Patient assessment included demographic information as well as medical and gynaecologic hystories with physical examination and routine laboratory screening (including BMI, CBC, Pap smear, TSH, PRL and viral serology).
The inclusion criteria were healthy women and absence of sexually transmitted disease, pelvic inflammatory disease or pregnancy. Patients with active vaginal bleeding were also excluded.
Hysteroscopy procedure: The patients of group 1 underwent hysteroscopy to rule out pathology of the endometrial cavity. During this procedure the endometrial cavity was examined for the presence of polyps or submucosal myoma or other pathologic conditions. Any projection inside the uterine cavity was observed with special attention to its shape and echo whether it was of polypoid like structure or type of myomas.
Ovarian stimulation: In order to ovarian stimulation in both groups, Clomifen (50-100 g day-1) and then after 5 days HMG (75 unit per day) were given. Between 12th and 14th day, trans vaginal sonography was done; if follicles were about 18-20 mm, single dose of HCG was used to induce ovulation.
IUI procedure: Semen specimens were washed using the swim up method and a single IUI using a volume of 0.3 mL was performed 36 h after rhCG injection. Pregnancy was documented by the serum hCG level 2 weeks after the insemination. If pregnant, a vaginal ultrasound was carried out 2-4 weeks later. The outcome of the pregnancy rate was determined by comparison of the pregnancy rate between two groups.
Comparison of the pregnancy rates between the two groups.
Statistical analysis: All data are expressed as the means±SEM. Chi-square test and t-test were used for comparison of the data of the infertile group versus the fertile group. P-value less than 0.05 were considered as significant difference.
A total of 110 cycles were randomized and available for investigation. None of the women refused to participate in the study. Fifty five patients were undergoing directly IUI and other women underwent hysteroscopy in the cycle before done IUI. The mean age of all of the patients was 32.3±4.5 years with a range of 22 to 44 years. The median duration of infertility of women was 4.7±1.4 years with a variety of 1.4 to 6.1 years. The two groups were found to be identical in the age, BMI, kind of infertility, duration of infertility, number of previous trial, duration of stimulation, the type of procedures used, the total dose of gonadotropin injected and semen analysis (TMC, Motility and morphology of sperm) (Table 1). Recorded no complications or difficulties in the performance of the hysteroscopy was recorded (none of the women had abdominal pain or nausea and no problems in insertion of the intrauterine insemination catheter into the cervical canal).
|| Comparison of characteristics of women in two groups
|| Comparison of findings from uterine evaluation experiment
|| Comparison of characteristics of women in two groups
In control group, three women had the failure in treatment and two abortions
happened too but in experiment group, three women had a failure in treatment,
and one abortion happened. No significant relation was found (Table
In experimental group, hysteroscopy revealed no pathology in the uterine cavity in 29 out of 55 patients. Oviduct tubes also were opened in all of patients. In the remaining 26 (47.27%), hysteroscopy evidenced, that surgery is needed due to some uterine disorder such as common pathologies: 13 (23.6%) abnormalities (uterine septum) related to the uterine cavity, 5 (9.3%) endometrial polyps, 5 (9.1%) cervical stenosis and 1 (1.8%) Ashermans syndrome (Table 2). In addition, we observed two patients presented more than one polyp lesion. No significant relation was found between pregnancy and type of pathology (p>0.835).
In the order of the clinical pregnancy between these two groups, the overall clinical pregnancy rates were lower for the control group 11(23.6%) compared to experimental group 22(23.6 %) (p<0.05. Table 1).
No significant undesirable reactions or surgical complication was reported in any of the patients. However, there were subjects of severe Ovarian Hyper Stimulation Syndrome (OHSS) in three patients in both groups and there was no significant difference (Table 3).
In general, preventing infertility is not easy and does not assist the couple
looking for therapeutic recommendation for infertility. Moreover, ART is time
consuming costly and the success rate is low and the failure rate is high (Bamgbopa,
2010; Lorusso et al., 2008). However, implementation
of infertility care in low-resource settings includes simplification of diagnostic,
i.e., hysteroscopy before ART procedures, can minimize the complication rate
of interventions (Ombelet et al., 2008; Madani
et al., 2009). Nonetheless, economic considerations and lack of capability
are thought to contribute to the lack of enthusiasm to employ hysteroscopy as
a routine investigative tool (Hinckley and Milki, 2004).
Unfortunately, although diagnostic and operative laparoscopy is well established
in gynecology, diagnostic hysteroscopy specifically in ART is, however, not
extensively employed in the ART clinic due to the unpleasantness created by
the course of action. Nevertheless, most researchers reported that the diagnostic
hysteroscopy is used in the extensive context of the infertility managing (Touboul
et al., 2009). However, Bozdag et al.
(2008) reported that the rates of incidence of uterine disorders in women
undergoing IVF, and in patients with known IVF failures were 18-50% and 40-43%,
respectively. Furthermore, endometrial polyps and uterine septum are more prevalent
in the infertile female than in the fertile ones (De Placido
et al., 2007; Di Spiezio Sardo et al.,
2008; Surrey et al., 2005). In the current
examine endometrial polyps and submucous myomas were observed as protuberances
into space of uterine through hysteroscopy as saying as well. This means that
hysteroscopy is a high-performance tool in discriminating anatomy of uterine
and in identifying congenital uterine disorders as well as in characterizing
points that are very worthy information through managing hysteroscopic surgical
of the lesions. Hucke et al. (2000) claimed that
uterine anomalies performed the critical role in infertility and showed the
uterine disorders that often lead to surgery are adhesion, uterine septum, endometrial
polyp, myoma, adenomyosis and cervical defect (Hucke et
al., 2000). Oliveira et al. (2003) and
La Sala et al. (1998) reported that of the 55
and 100 after IVF female undergoing diagnostic hysteroscopy, 25 (45%) and 18
(18%) cases respectively had abnormalities, which were treated (Oliveira
et al., 2003; La Sala et al., 1998).
Raju et al. (2006) also revealed that, in spite
of similarities in the mean number of oocytes retrieved, fertilization rate
and number of embryos transferred among IVF patients ruled in their study, the
clinical pregnancy rates in IVF patients that had abnormal office hysteroscopy
findings was lower than ones had normal hysteroscopy findings. Similarly, Demirol
and Gurgan (2004) suggested that patients with normal hysterosalpingography
but recurrent IVF-embryo transfer failure should be evaluated prior to commencing
IVF-embryo transfer cycle to improve the clinical pregnancy rate. Thus, it seems
that these studies along with the present study provide strong evidence for
including diagnostic hysteroscopy as part of the primary investigation of infertile
couple planned for assisted conception. modifications in the endometrial receptivity;
or diminished cross-talk between embryo-endometrium resulting in hindered implantation
and direct effect on the endometrium, leading to intrauterine fluid formation.
Strandell (2007), Mollo et al.
(2009) and Garbin et al. (2006) suggested
that the underlying mechanism explaining reduced implantation and embryo development
awaits further research. Kolankaya and Arici concluded that myomas that compress
the uterine cavity with an intramural portion and submucous myomas significantly
reduce pregnancy rates and should be removed before assisted reproductive techniques
and hysteroscopic myomectomy is the gold standard for the treatment of submucous
myomas (Kolankaya and Arici, 2006). In a different scenario,
Perez-Medina et al. (2005) reported that hysteroscopic
polypectomy before Intrauterine Insemination (IUI) achieves better pregnancy
outcomes than no intervention. (Perez-Medina et al.,
2005; El-Toukhy et al., 2008). Contrary to
the above-mentioned initiative results, some research declared that the hystroscopical
procedure (especially Hysteroscopy Surgery) was associated with a high prevalence
of complications, i.e., perforation of the uterine, intestine or urinary bladder
due to forceful manipulation of these organs, excess bleeding, increased fluid
absorption from the uterine into the vessels, infection and also death (Bradley,
2002; Pasini and Belloni, 2001). However, in the
current study, no notable undesirable reactions or surgical complication were
observed in any of the patients.
Hysteroscopy is efficacious as primary assessment in couples planned for ART. It is also the gold standard in the management of detected uterine anomalies. The application of hysteroscopy in assisted reproduction is rapidly evolving. There are, however many areas of hysteroscopy which require more research to enable the adoption of best practices in assisted reproduction.
This study was supported by a research grant from the Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. We acknowledge deputy vice-chancellor for research affairs of Ahvaz Jundishapur University Medical Sciences for financial support and particularly Research Consultation Center (RCC) for technical support.
1: Merviel, P., J.L. Mergui, S. Sananes, J.M. Antoine, J. Salat-Baroux and S. Uzan, 2000. Role of hysteroscopy in the diagnosis and treatment of infertility. Presse Med., 29: 1302-1310.
2: Valenzano, M.M., E. Mistrangelo, D. Lijoi, T. Fortunato and P.B. Lantieri et al., 2006. Transvaginal sonohysterographic evaluation of uterine malformations. Eur. J. Obstet. Gynecol. Reprod. Biol., 124: 246-249.
3: Isaacson, K., 2002. Office hysteroscopy: A valuable but under-utilized technique. Curr. Opin. Obstet. Gynecol., 14: 381-385.
Direct Link |
4: Breitkopf, D., S.R. Goldstein, J.W. Seeds and ACOG Committee on Gynecologic Practice, 2003. ACOG technology assessment in obstetrics and gynecology. Number 3, September 2003. Saline infusion sonohysterography. Obstet. Gynecol., 102: 659-662.
5: Hucke, J., F. De Bruyne and P. Balan, 2000. Hysteroscopy in infertility-diagnosis and treatment including falloposcopy. Contrib. Gynecol. Obstet., 20: 13-20.
6: Campo, R., C. Molinas, L. Rombauts, G. Mestdagh and M. Lauwers et al., 2005. Prospective multicentre randomized controlled trial to evaluate factors influencing the success rate of office diagnostic hysteroscopy. Human Reprod., 20: 258-263.
7: Darwish, A.M. and A.M. El-Saman, 2007. Is there a role for hysteroscopic tubal occlusion of functionless hydrosalpinges prior to IVF/ICSI in modern practice? Acta Obstet Gynecol. Scand., 86: 1484-1489.
8: Hitkari, J.A., S.S. Singh, H.M. Shapiro and N. Leyland, 2007. Essure treatment of hydrosalpinges. Fertil. Steril., 88: 1663-1666.
9: Mijatovic, V., S. Veersema, M.H. Emanuel, R. Schats and P.G.A. Hompes, 2010. Essure hysteroscopic tubal occlusion device for the treatment of hydrosalpinx prior to in vitro fertilization-embryo transfer in patients with a contraindication for laparoscopy. Fertil. Steril., 93: 1338-1342.
10: Bamgbopa, K.T., 2010. Hysteroscopy and assissted reproductive technology. Trop. J. Laparo Endosc., 1: 8-18.
11: Ombelet, W., I. Cooke, S. Dyer, G. Serour and P. Devroey, 2008. Infertility and the provision of infertility medical services in developing countries. Human Reprod. Update, 14: 605-621.
12: Hinckley, M.D. and A.A. Milki, 2004. 1000 office-based hysteroscopies prior to in vitro fertilization: Feasibility and findings. JSLS, 8: 103-107.
Direct Link |
13: Bozdag, G., G. Aksan, I. Esinler and H. Yarali, 2008. What is the role of office hysteroscopy in women with failed IVF cycles? Reprod. Biomed. Online, 17: 410-415.
14: De Placido, G., R. Clarizia, C. Cadente, G. Castaldo, C. Romano, A. Mollo, C. Alviggi and S. Conforti, 2007. Compliance and diagnostic efficacy of mini-hysteroscopy versus traditional hysteroscopy in infertility investigation. Eur. J. Obstet. Gynecol. Reprod. Biol., 135: 83-87.
Direct Link |
15: Oliveira, F.G., V.G. Abdelmassih, M.P. Diamond, D. Dozortsev, Z.P. Nagy and R. Abdelmassih, 2003. Uterine cavity findings and hysteroscopic interventions in patients undergoing in vitro fertilization-embryo transfer who repeatedly cannot conceive. Fertil. Steril., 80: 1371-1375.
16: La Sala, G.B., R. Montanari, L. Dessanti, C. Cigarini and F. Sartori, 1998. The role of diagnostic hysteroscopy and endometrial biopsy in assisted reproductive technologies. Fertil. Steril., 70: 378-380.
Direct Link |
17: Raju, G.A.R., G.S. Kumari, K.M. Krishna, G.J. Prakash and K. Madan, 2006. Assessment of uterine cavity by hysteroscopy in assisted reproduction programme and its influence on pregnancy outcome. Arch. Gynecol. Obstet., 274: 160-164.
18: Demirol, A. and T. Gurgan, 2004. Effect of treatment of intrauterine pathologies with office hysteroscopy in patients with recurrent IVF failure. Reprod Biomed. Online, 8: 590-594.
PubMed | Direct Link |
19: Strandell, A., 2007. Treatment of hydrosalpinx in the patient undergoing assisted reproduction. Curr. Opin. Obstet. Gynecol., 19: 360-365.
PubMed | Direct Link |
20: Kolankaya, A. and A. Arici, 2006. Myomas and assisted reproductive technologies: When and how to act? Obstet. Gynecol. Clin. North Am., 33: 145-152.
21: Perez-Medina, T., J. Bajo-Arenas, F. Salazar, T. Redondo, L. Sanfrutos, P. Alvarez and V. Engels, 2005. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: A prospective, randomized study. Human Reprod., 20: 1632-1635.
CrossRef | Direct Link |
22: Madani, T., F. Ghaffari, K. Kiani and F. Hosseini, 2009. Hysteroscopic polypectomy without cycle cancellation in IVF cycles. Reprod. Biomed. Online, 18: 412-415.
PubMed | Direct Link |
23: Touboul, C., H. Fernandez, X. Deffieux, R. Berry, R. Frydman and A. Gervaise, 2009. Uterine synechiae after bipolar hysteroscopic resection of submucosal myomas in patients with infertility. Fertil. Steril., 92: 1690-1693.
24: Di Spiezio Sardo, A., I. Mazzon, S. Bramante, S. Bettocchi, G. Bifulco, M. Guida and C. Nappi, 2008. Hysteroscopic myomectomy: A comprehensivereview of surgical techniques. Human Reprod. Update, 14: 101-119.
PubMed | Direct Link |
25: Surrey, E.S., D.A. Minjarez, J.M. Stevens and W.B. Schoolcraft, 2005. Effect of myomectomy on the outcome of assisted reproductive technologies. Fertil. Steril., 83: 1473-1479.
26: Mollo, A., P. De Franciscis, N. Colacurci, L. Cobellis and A. Perino et al., 2009. Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: A prospective controlled trial. Fertil. Steril., 91: 2628-2631.
27: Garbin, O., A. Ziane, V. Castaigne and C. Rongieres, 2006. Do hysteroscopic metroplasties really improve really reproductive outcome? Gynecol. Obstet. Fertil., 34: 813-818.
28: El-Toukhy, T., S.K. Sunkara, A. Coomarasamy, J. Grace and Y. Khalaf, 2008. Outpatient hysteroscopy and subsequent IVF cycle outcome: A systematic review and meta-analysis. Reprod. Biomed. Online, 16: 712-719.
29: Lorusso, F., O. Ceci, S. Bettocchi, G. Lamanna, A. Costantino, G. Serrati and R. Depalo, 2008. Office hysteroscopy in an in vitro fertilization program. Gynecol. Endocrinol., 24: 465-469.
PubMed | Direct Link |
30: Bradley, L.D., 2002. Complications in hysteroscopy: Prevention, treatment and legal risk. Curr. Opin. Obstet. Gynecol., 14: 409-415.
31: Pasini, A. and C. Belloni, 2001. Intraoperative complications of 697 consecutive operative hysteroscopies. Minerva Ginecol., 53: 13-20.