Intrauterine insemination (IUI) treatment in subfertility

Sinikka Nuojua-Huttunen

Department of Obstetrics and Gynaecology

Abstract

The effectiveness of intrauterine insemination (IUI) combined with controlled ovarian hyperstimulation (COH) in the treatment of subfertility was investigated in the present study. For this purpose the prognostic factors associated with success of clomiphene citrate (CC)/human menopausal gonadotrophin (HMG)/IUI were identified in 811 treatment cycles. Furthermore, a long gonadotrophin-releasing hormone agonist (GnRHa)/HMG stimulation protocol was compared with a standard CC/HMG protocol. In addition, the usefulness of alternative insemination techniques including fallopian tube sperm perfusion (FSP) and intrafollicular insemination (IFI) was investigated. Finally, the obstetric and perinatal outcome of pregnancies after COH/IUI was examined and compared with those of matched spontaneous and in vitro fertilization (IVF) pregnancies.

Female age, duration of infertility, aetiology of infertility, number of large preovulatory follicles and number of the treatment cycle were predictive as regards pregnancy after CC/HMG/IUI. The highest pregnancy rate (PR) was obtained in women of <40 years of age with infertility duration ≤6 years, who did not suffer from endometriosis. A multifollicular ovarian response to CC/HMG resulted in better treatment success than a monofollicular response, indicating the necessity of COH combined with IUI. A significantly higher PR was achieved in the first treatment cycles compared with the others, and 97% of the pregnancies were obtained in the first four treatment cycles.

The PR per cycle did not differ significantly between a long GnRHa/HMG and a standard CC/HMG protocol, but the average medication expense of GnRHa/HMG stimulation was four times the cost of CC/HMG stimulation. Therefore, the routine use of a long GnRHa/HMG protocol in IUI treatment remains questionable.

The FSP procedure was easy to perform by using a paediatric Foley catheter. The success rate in couples with either FSP or standard IUI did not differ significantly, although there was a trend towards a lower PR in the FSP group. The FSP technique should not replace the simpler and less time-consuming IUI technique in routine use.The IFI technique was also simple to perform and convenient for patients. However, only one normal singleton intrauterine pregnancy resulted in 50 IFI-treated women, indicating that IFI is inefficacious for treating subfertility.

The IUI parturients differed from average Finnish parturients in respect to higher maternal age, more frequent primiparity and a higher incidence of multiple pregnancies. The use of antenatal care services was significantly lower in IUI singleton pregnancies compared with IVF singletons, although there were no more complications in IVF pregnancies. The hospitalization and Caesarean section rates were generally high in all pregnancies. The mean birthweight of IUI singletons was significantly lower than that in spontaneous pregnancies, but comparable to that in IVF pregnancies. However, the incidence of preterm birth, low birth weight and other variables describing the outcome of infants were similar in IUI, IVF and spontaneous pregnancies. In summary, the IUI procedure itself does not seem to affect adversely the obstetric and perinatal outcome of pregnancy, and patient characteristics and multiplicity may be more important in this respect.


Dedication

Etsivä löytää.

To Mira, Henri and Osmo

Table of Contents
Acknowledgements
List of original publications
Abbreviations
1. Introduction
2. Review of the literature
2.1. Intrauterine insemination (IUI) treatment
2.1.1. Historical background
2.1.2. Ovarian stimulation with IUI
2.1.3. Stimulation protocols
2.1.4. Insemination techniques
2.1.5. Other factors affecting the outcome of IUI treatment
2.2. Obstetric and perinatal outcome of pregnancies after ART
3. Purpose of the present study
4. Materials and methods
4.1. Subjects
4.2. Study designs
4.3. Methods
4.3.1. Controlled ovarian stimulation and monitoring
4.3.2. Sperm preparation
4.3.3. Insemination techniques
4.4. Statistical analysis
5. Results
5.1. Factors affecting the outcome of CC/HMG/IUI treatment
5.1.1. Overall clinical results
5.1.2. Logistic regression
5.2. Comparison between GnRHa/HMG and CC/HMG protocols
5.3. IFI in the treatment of subfertility
5.4. Comparison between FSP and a standard IUI technique
5.5. Obstetric and perinatal outcome of IUI pregnancies compared with spontaneous and IVF pregnancies
5.6. The cost-effectiveness of CC/HMG/IUI treatment compared with IVF
5.7. IVF outcome in women with three or more unsuccessful CC/HMG/IUI cycles
6. Discussion
6.1. Factors affecting the outcome of CC/HMG/IUI treatment
6.1.1. Female age
6.1.2. Duration of infertility
6.1.3. Aetiology of infertility
6.1.4. Number of follicles
6.1.5. Number of the treatment cycle, and IVF after unsuccessful CC/HMG/IUI treatment
6.2. Usefulness of a GnRHa/HMG regimen in IUI treatment
6.3. Effectiveness of IFI and FSP techniques in the treatment of subfertility
6.3.1. Intrafollicular insemination
6.3.2. Fallopian tube sperm perfusion
6.4. Obstetric and perinatal outcome of pregnancies after COH/IUI treatment, and the cost-effectiveness of CC/HMG/IUI
7. Conclusions
References
List of Tables
2-1. A summary of studies on different protocols for COH.
2-2. Normal values of semen variables.
4-1. Summary of subject characteristics in studies I–V.
5-1. Pregnancy rate according to female characteristics in IUI treatment.
5-2. Pregnancy rate according to the number of preovulatory follicles and the number of the treatment cycle in IUI treatment.
5-3. Logistic regression model for predicting the success of IUI treatment.
5-4. Cycle characteristics, and pregnancy rates.
5-5. The number of progressively motile sperm in inseminates, and pregnancy rates.
5-6. Use of antenatal care and mother"s hospitalization during pregnancy, by plurality.
5-7. Outcome of newborns by plurality.