Nigerian Medical Journal

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 61  |  Issue : 6  |  Page : 312--315

Hysteroscopy findings after two previous failed In vitro fertilisation cycles: A case for routine hysteroscopy before In vitro fertilisation?


Jude Ehiabhi Okohue1, Sunday Omale Onuh2, Joy Ose Okohue1,  
1 Department of Obstetrics and Gynaecology, Assisted Reproduction Unit, Gynescope Specialist Hospital, Port Harcourt, Rivers State, Nigeria
2 Department of Obstetrics and Gynaecology, Assisted Reproduction Unit, Deda Hospital, Abuja, Nigeria

Correspondence Address:
Dr. Jude Ehiabhi Okohue
Assisted Reproduction Unit, Gynescope Specialist Hospital, Port Harcourt, Rivers State
Nigeria

Abstract

Background: The success rates of in vitro fertilisation (IVF) cycles have remained low. The condition of the uterus plays a significant role in the IVF treatment outcome. Unfortunately, some uterine pathologies are missed on routine ultrasound scans performed before IVF. Objective: To document the hysteroscopy findings following normal ultrasound scan endometrial assessments in women with two previous failed IVF cycles, seen at a private fertility unit. Materials and Methods: This is a retrospective descriptive study. The electronic medical records were retrieved for patients who underwent hysteroscopy after two consecutive failed IVF cycles despite normal ultrasound scan findings between April 1, 2010, and March 31, 2017. Data, including age, findings at hysteroscopy, and IVF/intracytoplasmic sperm injection treatment outcomes following hysteroscopy, were documented. The results are presented as frequency distribution tables. Results: A total of 77 patients had normal ultrasound scan findings after two previous failed IVF cycles, requiring a hysteroscopy during the study period. This represented 7.7% of the 1,002 hysteroscopies performed during the same period. The age range was 25–54 years, with a mean age of 37 ± 4.3 years. A majority of the women (59, 76.6%) had no pathology on hysteroscopy, while 14 (18.2%) had intrauterine adhesions. Three patients (3.9%) had endometrial polyps, and one patient (1.3%) had a subseptate uterus. Following hysteroscopy, 24 patients (31.2%) became pregnant, 29 patients (37.6%) had failed IVF cycles, while the remaining 24 patients (31.2%) were lost to follow up. Conclusion: This study has added to the body of evidence that suggests that routine hysteroscopy before IVF is capable of picking up missed pathologies that might otherwise negatively impart IVF success rates. More RCT are, however, needed to determine the effect of routine hysteroscopy on IVF treatment outcomes.



How to cite this article:
Okohue JE, Onuh SO, Okohue JO. Hysteroscopy findings after two previous failed In vitro fertilisation cycles: A case for routine hysteroscopy before In vitro fertilisation?.Niger Med J 2020;61:312-315


How to cite this URL:
Okohue JE, Onuh SO, Okohue JO. Hysteroscopy findings after two previous failed In vitro fertilisation cycles: A case for routine hysteroscopy before In vitro fertilisation?. Niger Med J [serial online] 2020 [cited 2021 Jan 26 ];61:312-315
Available from: https://www.nigeriamedj.com/text.asp?2020/61/6/312/304007


Full Text

 Introduction



Since the birth of Louise Brown in 1978, technologies involving in vitro fertilisation (IVF) have grown in leaps and bounds. The number of assisted reproductive technology (ART) cycles performed worldwide has continued to rise.[1] In 2015, ART contributed to 1.7% of all infants born in the United States of America.[2] Despite this, the success rate of each IVF and intracytoplasmic sperm injection (ICSI) cycle remains low.[1]

Embryo aneuploidy remains one of the most important contributors to poor IVF outcomes.[3] However, the condition of the uterus also plays a significant role in the success of IVF.[4],[5] Conditions such as polyps, fibroids, intrauterine adhesions, and uterine anomalies are known to interfere with fertility because they negatively impact sperm migration and embryo implantation.[6] Despite advances in technology, ultrasound scanning has been shown to miss certain uterine/endometrial pathologies that can be detrimental to IVF success.[6] Diagnostic hysteroscopy remains the gold standard for evaluating the uterine cavity.[7] There is no consensus regarding whether routine hysteroscopy improves the IVF success rate. While a 2014 meta-analysis showed that increased live birth rates were achieved after routine hysteroscopy in women scheduled for their first IVF cycle, another randomized controlled trial (RCT) published in 2015 showed a 70% improvement in the pregnancy rate in women scheduled for their first ICSI treatment cycle who underwent hysteroscopy before the treatment cycle.[8],[9] In contrast, one RCT (the TROPHY trial) that investigated the role of hysteroscopy in women with two to four failed IVF cycles concluded that hysteroscopy did not improve live birth rates.[10] A recent multicentre RCT also came to a similar conclusion.[11]

We, therefore, set out to document the hysteroscopic findings in women with normal ultrasound scan findings and two previous failed IVF cycles seen at a fertility unit in the Niger-Delta region of Nigeria, a country with highly restrictive abortion laws.

Objectives

To document the hysteroscopy findings following normal ultrasound scan endometrial assessments in women with two previous failed IVF cycles, seen at a private fertility unit.

 Materials and Methods



This is a retrospective descriptive study. The electronic medical records were retrieved for patients who underwent hysteroscopy after two consecutive failed IVF cycles despite normal ultrasound scan findings between April 1, 2010, and March 31, 2017. All the medical records were available. Data, including age, findings at hysteroscopy, and IVF/ICSI treatment outcomes following hysteroscopy, were documented. The results are presented as frequency distribution tables.

The choice of IVF treatment protocol was determined by the perceived response of the patient. While high responders used the antagonist protocol, normal and poor responders were managed with the gonadotropin-releasing hormone agonist (GnRH agonist) protocol.

The unit's protocol for endometrial assessment before the first IVF includes performing a transvaginal ultrasound scan during the proliferative phase of the menstrual cycle, using a two-dimensional (2D) vaginal probe with the endometrial cavity visualized in the longitudinal and transverse planes. All ultrasound scans were performed by a single certified sonologist with over 13 years of experience. All suspicious endometria were subjected to either hysterosalpingography (HSG) or saline infusion sonography (SIS). Hysteroscopy was subsequently performed when any abnormality was found. Following a failed IVF cycle, the same procedure for endometrial assessment was followed before a second, repeat IVF treatment.

Hysteroscopy was performed during the proliferative phase of the menstrual cycle using a 2.9 mm, 25° hysteroscope with a single compact inflow and outflow channels (Richard Wolf). All hysteroscopies were performed in an in-office setting under conscious sedation and intracervical lignocaine. Normal saline was used as distension media. All the pathologies were treated on a “see and treat” basis using 5F hysteroscopic scissors and graspers.

The Institutional Ethics Committee gave approval for the conduct of this study.

 Results



A total of 77 patients had normal ultrasound scan findings after two previous failed IVF/ICSI cycles and underwent a hysteroscopy during the study period. This represented 7.7% of the 1,002 hysteroscopies performed during the same period. As shown in [Table 1], the age range of the patients was 25–54 years, with a mean age of 37 ± 4.3 years.{Table 1}

[Table 2] shows the findings at hysteroscopy. The majority of the women (59, 76.6%) had no pathology on hysteroscopy, while 14 (18.2%) had intrauterine adhesions. Three patients (3.9%) had endometrial polyps, and one patient (1.3%) had a subseptate uterus. Following hysteroscopy, as shown in [Table 3], 24 patients (31.2%) became pregnant, 29 patients (37.6%) had failed cycles, and the remaining 24 patients (31.2%) were lost to follow-up. Of the 8 patients who underwent hysteroscopic adhesiolysis, 2 (25%) became pregnant.{Table 2}{Table 3}

 Discussion



Couples undergoing IVF/ICSI treatment cycles are burdened with anxiety and uncertainties following their first procedure.[12] Subsequent failure to achieve conception through IVF/ICSI has been shown to further worsen their quality of life.[13] For this reason, it is imperative from the outset that all efforts are put in place to ensure a successful outcome. This should include removing all known obstacles that could jeopardize their chances.

The age range of the patients was 25–54 years, with a mean age of 37 ± 4.3 years. It is the policy of the unit to set the upper age limit for offering treatment at 55 years of age. As shown in [Table 2], 23.4% of the women with two previous failed IVF/ICSI cycles showed abnormalities following hysteroscopy. Fatemi et al. reported finding previously unsuspected and missed intrauterine pathologies, including polyps, adhesions, septa, and fibroids, in 11% of women who planned to undergo IVF treatment.[6] Similarly, in a more recent study, Bahadur et al. evaluated 870 asymptomatic women enrolled for IVF. Among the 757 patients who had normal ultrasound scan findings, abnormal findings were observed in 108 patients (14.2%) following a hysteroscopic assessment of the endometrial cavity.[14] Cenksoy et al. reported a much higher figure of 44.9% for abnormal hysteroscopy findings in patients with two or more previous failed IVF cycles.[15]

The abnormality most frequently missed by the initial ultrasound scan was intrauterine adhesions. These were subsequently detected in 18.2% of the patients following hysteroscopy, further establishing the place of hysteroscopy as the gold standard for diagnosing intrauterine adhesions. In Nigeria, as in many countries with restrictive abortion laws, unsafe abortion is a significant problem.[7] Intrauterine adhesions are expected to be common in such a population. It is well established that intrauterine adhesions can be responsible for recurrent IVF/ICSI failure.[16] Even when implantation does occur, in a study carried out at a multi-disciplinary pregnancy loss prevention centre, intrauterine adhesions were reported to be the most common diagnosis in patients with recurrent pregnancy losses.[17] Intrauterine adhesions can also be responsible for some cases of cervical stenosis, which leads to difficult embryo transfer and a subsequent reduction in IVF success rates.[18],[19]

The effects of polyps on fertility, including the IVF/ICSI success rate, are conflicting as very few studies have been published, and they have reached different conclusions on this subject.[20] Only 3 (3.9%) patients had endometrial polyps that were missed on an initial ultrasound scan but later diagnosed following hysteroscopy. In a retrospective, descriptive study, polypectomy was the most common procedure performed in women with two or more previous failed IVF cycles, and this procedure produced a statistically significant increase in the pregnancy rate.[15] Although the effect of these polyps on IVF/ICSI success rates is not clear, if diagnosed before the commencement of a cycle, it is advisable that they be removed.[20]

Only one patient (1.3%) had a subseptate uterus (incomplete uterine septum). Similar to endometrial polyps, the effect of the uterine septum on infertility remains controversial as published results are both scarce and conflicting.[21],[22],[23],[24],[25] However, a recent cohort study suggested that the reproductive outcomes of IVF-ET after hysteroscopic correction for incomplete uterine septum in women with primary infertility were not different from those observed in women with a normal uterine cavity.[26] If left untreated, the septate uterus can result in preterm delivery and subsequent pregnancy wastage.[27]

Following hysteroscopy, there was a 31.2% clinical pregnancy rate, as shown in [Table 3]. Because it was hospital policy to carry out hysteroscopy following two failed IVF cycles, no patient who underwent another IVF treatment cycle without hysteroscopy were available for comparison. Cenksoy et al. reported a 48.1% pregnancy rate in women with abnormal but missed hysteroscopy findings after correction.[15] Of the eight women in our series who underwent hysteroscopic intrauterine adhesiolysis, two (25%) achieved a clinical pregnancy. Unfortunately, 24 (31.2%) of the patients were lost to follow-up, most likely because they could not continue for financial reasons or decided to patronize a different ART centre.

IVF and related procedures are expensive ventures to undertake. This is more so in developing countries where there is a fee for these services. In Nigeria, for example, over 70% of the population lives below the poverty line, which is <2 USD per day. The result is that the majority cannot afford an IVF treatment cycle. A few are able to afford just one cycle in their lifetime. While some are sponsored by communities, others have their bills paid for by religious organisations. This situation, coupled with the love for twins, probably explains why the majority of patients who undergo IVF/ICSI desire multiple pregnancies despite the attendant complications.[28] The argument for performing routine hysteroscopy before IVF/ICSI in such a population might sound justifiable because missed abnormalities might jeopardize their chances of success. Unfortunately, this procedure comes with added costs to the patient, and this might further worsen their financial situation.

 Conclusion



This study has added to the body of evidence that suggests that routine hysteroscopy before IVF is capable of picking up missed pathologies that might otherwise negatively impart IVF success rates. More RCT are however needed to determine the effect of routine hysteroscopy on IVF treatment outcomes, especially in a resource-poor environment with restrictive abortion laws. In the interim, the development of methods to provide low-cost hysteroscopy services would be welcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Ferraretti AP, Goossens V, Kupka M, Bhattacharya S, de Mouzon J, Castilla JA, et al. Assisted reproductive technology in Europe, 2009: Results generated from European registers by ESHRE. Hum Reprod 2013;28:2318-31.
2Sunderam S, Kissin DM, Crawford SB, Folger SG, Boulet SL, Warner L, et al. Assisted reproductive technology surveillance-United States, 2015. MMWR Surveill Summ 2018;67:1-28.
3Sills ES, Li X, Frederick JL, Khoury CD, Potter DA. Determining parental origin of embryo aneuploidy: Analysis of genetic error observed in 305 embryos derived from anonymous donor oocyte IVF cycles. Mol Cytogenet 2014;7:68.
4Okohue JE, Onuh SO, Ebeigbe P, Shaibu I, Wada I, Ikimalo JI, et al. The effect of endometrial thickness on in vitro fertilization (IVF)-embryo transfer/intracytoplasmic sperm injection outcome. Afr J Reprod Health 2009;13:113-21.
5Kader MA, Abdelmeged A. Mahran A, Samra MA, Bahaa H. The usefulness of endometrial thickness, morphology and vasculature by 2D Doppler ultrasound in prediction of pregnancy in IVF/ICSI cycles. Egypt J Radiol Nuclear Med 2016;47:34-46.
6Fatemi HM, Kasius JC, Timmermans A, van Disseldorp J, Fauser BC, Devroey P, et al. Prevalence of unsuspected uterine cavity abnormalities diagnosed by office hysteroscopy prior to in vitro fertilization. Hum Reprod 2010;25:1959-65.
7Okohue JE. Adhesions and abortion. In: Tinelli A, Alonso Pacheco L, Haimovich S, editors. Hysterocopy. Cham, Switzerland: Springer; 2018. p. 697-708.
8Pundir J, Pundir V, Omanwa K, Khalaf Y, El-Toukhy T. Hysteroscopy prior to the first IVF cycle: A systematic review and meta-analysis. Reprod Biomed Online 2014;28:151-61.
9Elsetohy KA, Askalany AH, Hassan M, Dawood Z. Routine office hysteroscopy prior to ICSI vs. ICSI alone in patients with normal transvaginal ultrasound: A randomized controlled trial. Arch Gynecol Obstet 2015;291:193-9.
10El-Toukhy T, Campo R, Khalaf Y, Tabanelli C, Gianaroli L, Gordts SS, et al. Hysteroscopy in recurrent in vitro fertilization failure (TROPHY): A multiculture randomnised controlled trial. Lancet 2016;387:2614-21.
11Smit JG, Kasius JC, Ejikemans MJ, Koks CA, Van Golde R, Nap AW, et al. Hysteroscopy before in vitro fertilization (in SIGHT): A multicenter randomized controlled trial. Lancet 2016;387:2622-9.
12Karaca N, Karabulut A, Oz Kan S, Aktun H, Orengul F, Yilma R, et al. Effect of IVF failure on quality of life and emotional status in infertile couples. Eur J Obstet Gynecol Reprod Bio 2016;206:158-63.
13Maroufizadeh S, Ghaheri A, Omani Samani R. Factors associated with poor quality of life among Iranian infertile women undergoing IVF. Psychol Health Med 2017;22:145-51.
14Bahadar A, Malhotra N, Singh N, Gurunath S, Mittal S. Comparative study on the role of diagnostic hysteroscopy in evaluation of the uterine cavity prior to in vitro fertilization in a developing country. Arch Gynecol Obstet 2013;288:1137-43.
15Cenksoy P, Ficicioglu C, Yıldırım G, Yesiladali M. Hysteroscopic findings in women with recurrent IVF failures and the effect of correction of hysteroscopic findings on subsequent pregnancy rates. Arch Gynecol Obstet 2013;287:357-60.
16Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: Definition and management. Reprod Biomed Online 2014;28:14-38.
17Young BK. A multidisciplinary approach to pregnancy loss: The pregnancy loss prevention centre. J Perinal Med 2018;47:41-4.
18Mathew M, Mohan AK. Recurrent cervical stenosis - A troublesome clinical entity. Oman Med J 2008;23:195-6.
19Larue L, Keromnes G, Massari A, Roche C, Bouret D, Cassuto NG, et al. Anatomical causes of difficult embryo transfer during in vitro fertilization. J Gynecol Obstet Hum Reprod 2017;46:77-86.
20Afifi K, Anand S, Nallapeta S, Gelbaya TA. Management of endometrial polyps in subfertile women: A systematic review: Eur J Obstet Gynecol Reprod Bio 2010;151:117-21.
21Grimbizis GF, Camus M, Tarlatzis BC, Bontis JN, Devroey P. Clinical implications of uterine malformations and hysteroscopic treatment results. Hum Reprod Update 2001;7:161-74.
22Rackow BW, Arici A. Reproductive performance of women with müllerian anomalies. Curr Opin Obstet Gynecol 2007;19:229-37.
23Heinonen PK. Complete septate uterus with longitudinal vaginal septum. Fertil Steril 2006;85:700-5.
24Pabuçcu R, Gomel V. Reproductive outcome after hysteroscopic metroplasty in women with septate uterus and otherwise unexplained infertility. Fertil Steril 2004;81:1675-8.
25Shokeir T, Abdelshaheed M, El-Shafie M, Sherif L, Badawy A. Determinants of fertility and reproductive success after hysteroscopic septoplasty for women with unexplained primary infertility: A prospective analysis of 88 cases. Eur J Obstet Gynecol Reprod Biol 2011;155:54-7.
26Abuzeid M, Ghourab G, Abuzeid O, Mitwally M, Ashraf M, Diamond M. Reproductive outcome after IVF following hysteroscopic division of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility. Facts Views Vis Obgyn 2014;6:194-202.
27Tomaževič T, Ban-Frangež H, Virant-Klun I, Verdenik I, Požlep B, Vrtačnik-Bokal E. Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI. Reprod Biomed Online 2010;21:700-5.
28Okohue JE, Onuh SO, Ikimalo JI, Wada I. Patients' preference for number of embryos transferred during IVF/ICSI: A Nigerian experience. Niger J Clin Pract 2010;13:294-7.