Indication of intravaginal insemination for infertility treatment in couples with sexual dysfunction

Abstract Purpose To analyze the usefulness of intravaginal insemination (IVI) for the infertility treatment in couples with sexual dysfunction before applying assisted reproductive technology (ART). Methods Among 208 couples who presented sexual dysfunction, 144 couples underwent IVI procedures. The profiles of pregnant and non‐pregnant patients were compared. Results Of 144 patients, 58 women conceived successfully (40.3% pregnancy rate). Between the pregnant and non‐pregnant cases, the husband's age and infertility period were significantly higher (P = .0104) and longer (P = .0027) in the unsuccessful cases than the successful ones. The husbands who could not impregnate had a significantly higher ratio of sperm abnormalities (P = .0048). Among the 57 successful cases who underwent IVI treatment, 38 (66.7%) patients became pregnant within 3 times of the procedure, while 48 (84.2%) patients conceived within 6 times. Conclusion The authors can propose the following inclusion IVI criteria for couples with sexual dysfunction: (a) younger husband (36 years old or less) which may be most important, (b) infertility duration of 3 years or less, (c) normal sperm condition, and (d) IVI trial for 3 times (maximum of 6 times). Since IVI appears to be a simple, noninvasive, and inexpensive way for couples with sexual dysfunction, it can be attempted before ART application.

it possible to conceive without coitus. Intrauterine insemination (IUI) is widely used as the treatment method for mild male factor and unexplained infertilities. 5 In vitro fertilization (IVF) and a microinsemination of intracytoplasmic sperm injection (ICSI) are further applied; more than 465,000 babies were born in 2012 using these technologies throughout the world. 6 Although ART is very effective as an infertility treatment, IUI can be painful when a speculum is inserted into the vagina and further, women are required to visit the clinic repeatedly. IVF and ICSI also involve burdensome processes such as ovarian stimulation by gonadotropins, frequent clinic visits to follow the follicle growth, and oocyte retrieval under anesthesia, In addition, IUI, IVF, and ICSI are all expensive with a cost of about 10 000-30 000, 200 000-500 000, and 300 000-600 000 yen, respectively, without national health insurance coverage in Japan.

Contrarily, intravaginal insemination (IVI) as an artificial home
vaginal insemination is a simple, noninvasive, and inexpensive method, which does not require frequent doctor visits. IVI can be performed personally at home in a private room, and does not impact marital activities. IVI may further be applied to treat couples with sexual dysfunction if semen can be obtained by the husband through masturbation. Pregnancy should be achieved without penile insertion into the vagina in an unconsummated marriage.
Although many studies regarding IVI on ejaculatory dysfunction have been reported, only a few studies on the effectiveness of IVI as an infertility treatment for couples with general sexual dysfunction, especially ED, are available. Our clinic, which is specialized in infertility management for more than 10 years, has helped many patients, including couples with sexual dysfunction. Thus, the authors analyzed the usefulness of IVI before applying ART and proposed the inclusion criteria of IVI as a treatment method for infertility.

| Patients
Between January 2009 and December 2018, 5034 couples first visited Kaseki Ladies Clinic for infertility treatment. Among these patients, 208 couples presented sexual dysfunction; 199 husbands indicated ED and/or inhibited ejection, and 20 wives had vaginismus and dyspareunia. Seventeen men had been treated with anti-phosphodiesterase-5 medicines such as sildenafil, vardenafil, and/or tadalafil. Some couples had received psychological sex counseling from specialists.
Other complications such as depression, hypertension, spinal cord injury (SCI), and cerebral infarction were observed in males, while among the wives, polycystic ovary syndrome, endometriosis, uterine myoma, ovarian cysts, and depression were present in 20, 7, 6, 4, and 3 cases, respectively. Fifty-eight women had previously been pregnant and 47 had given birth. Four cases lost the ability to have sexual intercourse after delivery.
Inclusion criteria for the IVI treatment were as follows: (a) consent to undergo IVI treatment at home, (b) ability to collect sufficient volume of semen, and (c) an age of over 20 years for both husband and wife. Exclusion criteria were as follows: (a) non-agreement for IVI, (b) inability to collect semen, (c) azoospermia, severe oligospermia, or evidential asthenozoospermia, and (d) absolute tubal or uterine factor infertility.
Any personal information in the clinical medical records used in this retrospective study was kept confidential, and all data were anonymized. Subsequently, the data sheet was transferred to the analyzer to sort out the data and analyze statistically. All these procedures were approved by the Ethical Committee at the Kaseki Ladies Clinic (R2-01).

| Intravaginal insemination procedure
After obtaining informed consent from the patients, 5-10 sets of a sterile semen container (Multipurpose Beaker, 100 mL, Greiner Bio-One International) and 1-cc syringe (Terumo Corporation) were given to the couples. The IVI method was explained orally by the clinicians using a method sheet prepared by our clinic. The IVI procedure was performed at the time of ovulation, which was determined by transvaginal ultrasound imaging or by the couples themselves during the general menstrual cycle. When necessary, ovulation induction was performed using medicines such as clomiphene citrate (CC), human follicle-stimulating hormone (FSH), or human menopausal gonadotropin (hMG). After the semen was collected in the container by masturbation, it was aspirated into the syringe and injected into the wife's vagina at home. These procedures were performed twice (up to 2 mL), and the wife then rested for about 15 minutes in the supine position.
The patient was asked to return to our clinic when the pregnancy test was positive or all the sets of semen container and syringe were used.
No troubles in IVI procedure were complained by the couples.

| IUI and IVF/ICSI
ART was applied in the usual method at our clinic. IUI was performed using the swim-up sperm. Ovarian stimulation with CC, FSH, or hMG, gonadotropin-releasing hormone analog treatment, human chorionic gonadotropin injection, oocyte collection, sperm preparation, IVF, ICSI, and fresh or cryopreserved-thawed embryo/blastocyst transfer were performed mainly according to the standard methods used in Japan. 7

| Statistical analysis
To compare between pregnant and non-pregnant cases who underwent IVI, Student's t test, chi-square test, or the Cox regression proportional hazard model was applied for statistical analysis using SPSS Statistics, version 25 (IBM Japan, Tokyo, Japan). A P-value of <.05 was considered statistically significant.

| Patient profiles
Because 12 of the 156 couples who received IVI instruments did not visit our clinic again, the outcome of IVI treatment among the remaining 144 cases was analyzed ( Figure 1). Results showed that 58 women conceived successfully as a pregnancy rate (PR) of 40.3%.
A comparison of the pregnant and non-pregnant cases showed that the husband's age and infertility period were significantly higher (P =.0104) and longer (P =.0027) in the unsuccessful cases than the successful ones (Table 1). There was no difference in pregnancy achievement among the couples who had male factors, female factors, or both (P =.2526). The number of IVI performances was not different in the both groups (P =.9941). The husbands who could not impregnate had a significantly higher ratio of sperm abnormalities such as asthenozoospermia and oligospermia (P =.0048). Ovulation induction with CC, FSH, and/or hMG was performed significantly more in pregnant women (P =.0161).

| Number of IVI procedures until pregnancy
The number of IVI treatment performed until pregnancy in the successful cases is summarized in

| Cox regression proportional hazard model
Analysis using the Cox regression proportional hazard model was performed. Because regression equation indicated as P =.003, the regression equation for each parameter was analyzed subsequently. Table 3, the hazard ratio of husband's age indicated a significant relation with the outcomes of IVI.

| Outcomes by other ART treatments
The couples who could not become pregnant by IVI were treated using other ARTs (Figure 1)

| D ISCUSS I ON
For a long time, IVI has been applied to treat ejaculatory dysfunction. 8  In conclusion, the authors propose the following inclusion criteria of IVI as an infertility treatment for couples with sexual dysfunction: (a) younger husband (36 years old or less), (b) infertility duration of 3 years or less, (c) normal sperm condition, and (d) IVI trial up to 3 times (maximum of 6 times). Among these proposals, husband's age may be the most important factor for the IVI outcomes though the reason will be able to be revealed in further study. IVI at home seems to be a simple, noninvasive, and inexpensive way for couples with sexual dysfunction to get pregnant; it can hence be attempted before IUI and/or IVF/ICSI are applied. Note: Cox regression proportional hazard model was applied.

TA B L E 3 Relation of each parameter to the IVI outcomes
Abbreviation: IVI, intravaginal insemination.