OUTCOME OF 50 CONSECUTIVE INTRAUTERINE INSEMINATION PROCEDURE AT A PRIVATE FERTILITY CENTER IN ONDO, SOUTH WEST NIGERIA (PARAMOUNT SPECIALIST HOSPITAL & FERTILITY CENTRE, ONDO STATE) ADEMULEGUN, TOLULOPE EBENEZER AKINDOJUTIMI JERRIE AKINWOLE KOLAWOLE AKINMADE OLAMIPOSI LOTO OLABISI Presented at The 7th Annual AFRH International Conference Abuja 2017

OVERVIEW INTRODUCTION AIM/OBJECTIVE OF STUDY STUDY DESIGN/SETTING MATERIALS AND METHOD RESULTS DISCUSSIONS CONCLUSION

INTRODUCTION IUI is a procedure that places washed active sperm past the cervix and in a woman’s uterus around the time of ovulation. Better chance that more sperm will encounter the egg. The goal of this procedure is to improve a woman’s chance of getting pregnant.

INTRODUCTION (contd) The use of IUI for the management of infertility underwent a decline following the emergence of the HIV as well as the complications associated with the use of neat semen. The use of washed prepared sperm for IUI has also resulted in a significant reduction in the side effects associated with the use of neat semen for IUI such as painful uterine cramps, collapse and infection.

AIM/OBJECTIVE OF STUDY Documenting prognostic factors that can be used in decision making and patient counselling.

STUDY DESIGN / SETTING Retrospective study Private fertility clinic in Ondo, Nigeria Data collected between February 2016 to January 2017

MATERIALS AND METHOD Patient counselled and enrolled. Consent

MATERIALS AND METHOD II Semen analysis Ovulation induction was carried out with Clomiphene citrate (CC) 100mg daily for 6 days alone, or in combination with Metformin 500mg BD for 10days or Letrozole 2.5mg daily for 6 days; Letrozole in combination with Metformin: and stimulation with human menopausal gonadotrophin 75 IU daily for 10 days starting from day 2–5 of the menstrual cycle. The ovarian response to stimulation was monitored by transvaginal ultrasound assessment of follicular and endometrial growth on days 9 and 11 of menstrual cycle. A pre-human chorionic gonadotrophin (pre-hCG) scan was done on day 11 or 12 and ovulation triggered by a single injection of 5,000 IU of human chorionic gonadotrophin when at least a matured sized follicle had reached the diameter of ≥ 18mm and trilaminar endometrial thickness of 8 – 12mm. Intrauterine Insemination was then carried out between 36 – 40 hours post-hCG trigger.

Semen collection by masturbation (or coitus interruptus with spermicide- free condoms where masturbation is not possible) Sperm wash technique with density gradient sperm preparation

The patients were placed in lithotomy position, cleaning of the perineum, vulva and vagina was done with normal saline and Sterile speculum was inserted to expose the cervix. The washed sperm is suspended in 0.3 to 0.5ml of media and then injected into the uterus slowly. The patients rest for 15minutes after insemination. Normal sexual intercourse was encouraged within the next 72 hours.

Commencement of luteal phase support on 5th day post-insemination with progesterone Biochemical pregnancy was determined by maternal serum bHCG level on day 15 post-insemination, while clinical pregnancy was confirmed by ultrasound detection of a gestational sac at 4 weeks post-insemination

Primary end-point was the live birth rate (per insemination). The secondary end-points were chemical and clinical pregnancy rates, spontaneous abortion rates and age distribution rates. The data regarding pregnancy follow-up and delivery were also extracted The results were analyzed by Statistical Package for Scientific Solutions (SPSS) software version 17.0

TABLE I TABLE 1: PREGNANCY RATE FOLLOWING 50 TREATMENT CYCLE OF INTRAUTERINE INSEMINATION OUTCOME FREQUENCY PERCENT NON PREGNANT 40 80.0 ABORTION 3 6.0 ECTOPIC 1 2.0 LIVEBIRTH 6 12.0 TOTAL 50 100.0

TABLE 2 TABLE 2: FACTORS AFFECTING THE PREGNANCY RATES IN INTRAUTERINE INSEMINATION PARAMETERS OUTCOME FREQUENCY (%) P VALUE Female Age (years) Non-Pregnant Pregnant   0.490 20-24 25-29 30-34 35-39 40-44 1 4 15 17 3 1(2) 7(14) 18(36) 21(42) 3(6) Parity 0.317 2 29 6 10 39(78) 6(12) 4(8) 0(0) Cause of Infertility 0.749 Ovulatory Tubal Cervical Male Unexplained 8 13 9(18) 5(10) 13(26) 16(32)

TABLE 3 OVULATION INDUCTION AGENT NON-PREGNANT PREGNANT   0.987 CC alone CC + Metformin CC + Letrozole Letrozole + Metformin HMG Natural cycle 15 7 3 1 13 4 2 19(38) 9(18) 4(8) 1(2) 16(32) INSEMINATION TIME (HOURS) 0.845 <36 36-38 38-40 >40 12 25 15(30) 32(64) 2(4) POST WASH SPERM CONCENTRATION(MILLION/ML) 0.006 <20 21-40 41-60 61-80 81-100 >100 6 10 6(12) 11(22) 3(6) 10(20)

DISCUSSION In our study the trend towards reduction in success rate with ovulation induction and IUI was noted in women with age >40 years, although the difference was not statistically significant. This may be due to the small sample size. Many studies have documented a significant drop in the success rate beyond the age of 40 years, with reported live births being as low as 1.4%.4 Put together, for women over 35 years, ovulation induction and IUI as a treatment option needs careful consideration, and for women over 40, IUI is a poor treatment option.

Among indications for IUI, the success rate was higher in male factor (use of donor sperm) and unexplained infertility as compared with tubal and ovulatory factors, although the difference did not reach statistical significance. Some studies found that unexplained infertility had a better prognosis in clinical pregnancy compared to other etiological factors. However, some studies noted that moderate male factors and anovulation have the highest clinical pregnancy rates in IUI.

Our study showed that patients with sperm concentration >80 million had better pregnancy outcome. The clinical pregnancy rate was increased in sperm count ≥ 80 million per ml (P=0.006). In most studies, the density gradient method has been shown to confer advantages in sperm recovery compared to swim-up method This method not only yields the highest number of motile sperm but also reduces the bacterial contamination and processing time.13 Furthermore, this technique has a higher percentage of morphological sperm recovery, better DNA quality and chromatin packaging.

CONCLUSION Ovulation Induction and IUI is an important treatment option for varied indications, especially when female age is <35 years. The female age and sperm concentration have the most predictive value for IUI clinical pregnancy outcome in our center.