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. 2024 Sep 30;14(9):2348–2360. doi: 10.5455/OVJ.2024.v14.i9.23

Biocompatibility assessment of an integrated contraceptive and RFID-based intravaginal device in cats (Felis catus): A preliminary study

Muhammad Irham Bagus Santoso 1, Sella Sofia Ainun 1, Dian Utami 1, Fathan Abdul Aziz 1, Resti Puspitaningsih 1, Yaomil Ashar 1, Gunanti Gunanti 2, Murni Nazira Sarian 3, Mokhammad Fakhrul Ulum 5,*
PMCID: PMC11563625  PMID: 39553770

Abstract

Background:

An intravaginal device (IVD) made from polyethylene plastic and copper wire, integrated with a radio frequency identification (RFID) chip, was developed as a biocompatible contraceptive and identity device for cats.

Aim:

This study evaluates the local and systemic biocompatibility of IVD in five non-pregnant female cats.

Methods:

The IVD was successfully inserted into the vaginal lumen after estrogen administration. Radiographic imaging confirmed the IVD’s position, which lasted up to two days post-insertion.

Results:

Systemic response, assessed through hematological examinations on days 0, 1, and 3 post-insertion, showed no significant changes in erythrogram and leukogram parameters. Local response, evaluated through vulvar inspection and vaginal cytology on days 0, 1, 3, and 7, revealed no neutrophil infiltration in 4 out of 5 cats, indicating compatibility with vaginal tissue. Furthermore, epithelial cell profile changes were observed, showing an increase in superficial cells, which is typical during the estrus phase.

Conclusion:

These findings suggest that the IVD is biocompatible and suitable for use as a contraceptive and identity device in cats. However, further long-term studies are necessary to evaluate the device’s prolonged efficacy and potential for contraception failure prevention by mating trials.

Keywords: Intravaginal device, Biocompatibility, Contraception, RFID identification, Feline population control

Introduction

The growing population of cats requires urgent attention due to its potential to cause public discomfort and increase the risk of zoonotic disease transmission (Madyantari et al., 2016). Traditional population control methods, such as castration for males and ovariohysterectomy for females, involves removing reproductive organs via surgery. While effective in some contexts, these methods face significant field obstacles, including post-surgical complications, increased risk of neoplasia, musculoskeletal disorders, and hormonal imbalances (Kustritz, 2012; Hekman, 2020).

Current contraceptive options for cats, including surgical spaying and chemical contraceptives, have notable limitations such as the need for anesthesia, high costs, and potential side effects (Nielsen et al., 2022). Non-surgical methods, such as immunocontraceptives, hormonal contraceptives, chemical contraceptives, physical reproductive barriers, and gene delivery, offer promising alternatives but often remain costly and impractical for large-scale applications (Cathey and Memon, 2010; Vansandt et al., 2023). The development of an innovative, less invasive, and cost-effective solution like the intravaginal device (IVD) integrated with RFID technology is necessary to address these challenges (Boone et al., 2019).

An intrauterine device (IUD) is commonly used in humans and some animals for contraception, operating through mechanisms such as sperm motility disruption and spermicidal activity of released metal ions (Winner et al., 2012). Despite successful applications in other species, adapting IUDs for cats has been difficult due to the anatomical structure of the feline cervix (Aspinall, 2011). Radio frequency identification (RFID) technology has been extensively used for identification, tracking, storing, and retrieving data via radio waves (Suresh and Chakaravarthi et al., 2012). Typically, RFID is used for tracking animal whereabouts, conducting animal censuses, and maintaining medical records (Lord et al., 2007). Implanting RFID in animals is commonly performed subcutaneously or in other body parts (Gillenson et al., 2019), and it serves purposes such as tracking (Fong et al., 2023), behavior assessment (Alindekon et al., 2023), and physiological monitoring (Ahmmed et al., 2024). Integrating RFID with a contraceptive device could provide dual functionality, facilitating both contraception and animal identification.

Due to the anatomical challenges of the feline cervix, which consists of tightly closed sphincter muscles with a narrow lumen (Aspinall, 2011), this preliminary research explores the insertion of an IVD in the vaginal lumen. The aim is to control cat populations by placing the contraceptive device in the vaginal lumen as a controlled internal drug release (CIDR) system.

Recent advances in RFID technology have facilitated its integration into various veterinary applications, including identification and health monitoring (Pereira et al., 2023). Combining RFID technology with contraceptive devices offers significant benefits for population control and efficient animal tracking, which is critical for managing stray and feral cat populations (Hamer et al., 2021). Furthermore, studies have demonstrated the effectiveness of non-surgical contraceptive methods in reducing feral cat populations with fewer welfare concerns compared to traditional methods (Hekman, 2020).

Materials implanted in the body must meet stringent biocompatibility standards, evaluated based on local and systemic cytotoxicity, as well as the potential to cause allergic reactions or carcinogenicity (Anusavice, 2003). Ensuring biocompatibility is crucial for any implanted device to avoid adverse immune responses or local tissue damage, especially for contraceptive devices that need to remain in place for extended periods (Williams, 2008; Anderson et al., 2008).

This study aims to develop and test the biocompatibility of an integrated contraceptive and RFID-based IVD in cats, addressing the need for a novel, practical solution for feline population control. We focus on evaluating both the local and systemic biocompatibility of this innovative IVD by analyzing hematological parameters and conducting cytological evaluations to confirm its safety for long-term use in felines (Nasution et al., 2018). The successful implementation of this device could offer a non-surgical solution for controlling cat populations while improving identification and monitoring practices.

Materials and Methods

Animals

This study involved five female cats aged between 1.0 and 1.5 years, with body weights ranging from 1.5 to 2.5 kg.

Pregnancy examination

To confirm that the five clinically healthy female cats were not pregnant prior to IVD insertion, ultrasound examinations (Sonodop S3X, China) using a 7.5 MHz linear array transducer were performed. The cats’ abdominal areas were shaved, the gel was applied for better imaging, and the transducer was used to locate the uterus in a dorsal recumbency position (Fig. 1).

Fig. 1. Results of ultrasound examination of reproductive organ status in five cats that were not pregnant before IVD contraception was installed. (a) 1st cat, (b) 2nd cat, (c) 3rd cat, (d) 4th cat, and (e) 5th cat. Note: UT = uterus, VU = urinary bladder.

Fig. 1.

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Acclimatization and maintenance of the experimental animals

The cats were acclimatized for seven days in individual cages. On the first day of acclimatization, anthelmintic and anti-ectoparasitic ivermectin (Intermectin, Holland) was administered subcutaneously at a dose of 0.02 ml/kg body weight. On the second day, vitamin B complex (Supra Ferbindo Farma, Indonesia) was given orally. The cats were fed with a combination of wet (Whiskas, Indonesia) and dry (Bolt Copetindo, Indonesia) cat foods in the morning and evening, with water provided ad libitum throughout the acclimatization and study period.

Fabrication of IVD

The IVD was constructed using two main materials: copper wire with a diameter of 0.2 mm and a polyethylene pipe. The polyethylene pipe measured 1 cm in length with a diameter of 0.3 mm. Copper wire was wound around the surface of the polyethylene pipe for 0.5 cm. An RFID chip (Star Security Technologies, China) was inserted into a segment of the polyethylene pipe that did not contain copper coils. Nylon with a diameter of 0.1 mm and 2 cm in length was added to both ends of the pipe and formed into an oval shape using a hot hair dryer (Philips Hair Dryer, China). The assembled device was glued with cyanoacrylate (Dextone, PT Dextone Lemindo, Indonesia) and sterilized using a UV sterilizer (PSKY, China) for one hour before insertion (Fig. 2).

Fig. 2. Fabrication of the IVD used in research cats. (a) Parts of the IVD, (b) side view, (c) bottom view, and (d) top view. Note: 1 = Nylon Backing, 2 = Copper wire winding, 3 = RFID Chip, and 4 = Nylon Marker.

Fig. 2.

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Insertion of IVD

One week after acclimatization, the IVD was inserted into the vaginal lumen using aseptic techniques. Cats were pre-treated with an intramuscular injection of estrogen (Ovalumon, PT Wonderindo Pratama, Indonesia) at a dose of 0.5–1.5 mg/kg body weight (Leyva et al. 2014) three hours before IVD insertion to relax the vaginal muscles. Premedication with atropine (Atropine Sulfate, PT Ethica Industri Farmasi, Indonesia) at a dose of 0.025 mg/kg body weight was administered 10 minutes before anesthesia. The cats were then anesthetized using a combination of ketamine (Ilium Ketamil, Holland) at a dose of 10 mg/kg body weight and xylazine (Xyla, Holland) at a dose of 2 mg/kg body weight, administered intramuscularly (Hellebrekers, 1996). The IVD was inserted using an applicator tube, which was advanced to the cervix, and the IVD was then deployed into the vaginal lumen by pressing the piston (Fig. 3). The insertion process was monitored using an RFID reader (Star Security Technologies, China).

Fig. 3. Process of insertion of IVD in the vagina and monitoring ID in cats. (a) IVD insertion process: (b) insert IVD, (c) radiographic imaging of contraceptives that have been inserted, and (d) Read RFID identity on those that have been inserted.

Fig. 3.

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Radiographic examination

Vaginal contrast radiography was conducted to measure the size of the vaginal lumen. A 1 ml contrast agent (Iohexol, 35 ml infusion, Indonesia) was administered intravaginally. The contrast material was inserted by lifting the ventral part of the sacrum to form an angle of approximately 60º, ensuring that the caudal body of the cat was higher than the cranial part. 1 ml of positive contrast material was then slowly inserted into the vaginal lumen using a 1 ml syringe. Radiographs were taken with an exposure factor of 52 kVp and 1.2 mAs at lateral and ventrodorsal angles using a radiography machine (VR 1020, Japan). Post-contrast, the vaginal lumen was flushed with physiological saline (Otsu-NS®, PT Otsuka Indonesia) to remove residual contrast material. Radiographs were repeated on days 3 and 7 post-insertion to confirm IVD placement.

Vulva photography

Photographic documentation of the vulva was performed using a smartphone camera (ASUS Zenfone Max Pro M1, Taiwan) to observe changes in mucous discharge, color, and swelling. Photographs were taken the day before and after IVD insertion in the vaginal lumen.

Blood sample examination

Blood samples were collected on days 0, 1, and 3 post-insertion of the IVD into the vaginal lumen. Cats were premedicated with atropine (0.025 mg/kg body weight) and anesthetized using ketamine (10 mg/kg body weight) and xylazine (2 mg/kg body weight) as previously described (Hellebrekers, 1996). The lateral part of the foreleg was disinfected with 70% alcohol cotton. Blood samples were taken from the dorsal antebrachial cephalic vein (1 ml) using a syringe (One Med, Indonesia). The blood was placed in 3 ml ethylenediaminetetraacetic acid vacutainer tubes (Intherma Vacuum, Indonesia), homogenized, and stored in a cooling box for delivery to the Commercial Laboratory at Klinik Medialisa Bogor for hematological analysis using a hematology analyzer.

Cytological observation of vaginal epithelial cells

Vaginal cytology was performed on days 0, 1, 3, and 7 post IVD insertion. The female cat’s vagina was swabbed using a cotton swab (Baby Huki, Indonesia) moistened with distilled water. The tip of the cotton swab was inserted into the vulva at an upward angle to enter the vaginal lumen, then straightened forward to a depth of 1 cm (Pratiwi et al., 2018). Swabs were taken by rotating the tip of the cotton swab clockwise 2–3 times. The tip of the cotton swab was then attached to a glass slide (Sail Brand, China) and rotated slowly to transfer the vaginal epithelial cells onto the glass slide. The swab results on the slide were fixed using methanol for 5 minutes and stained with 10% Giemsa dye (Merck KGaA, Germany) for 30 minutes. The stained slides were then observed using a light microscope (Olympus Binocular Microscope, Olympus Corp, Japan) with 10x magnification.

Data analysis

Data were analyzed using the statistical package for the social sciences (SPSS) software application version 25. Differences in blood profiles between observation times were tested using the independent T-test, while differences in vaginal cytology profiles between observation times were tested using one-way ANOVA followed by the Post Hoc Duncan test with a 95% confidence interval.

Ethical approval

The research protocol received approval from the Commission for Supervision of Welfare and Use of Experimental Animals at the Veterinary Teaching Hospital (RSHP), School of Veterinary Medicine and Biomedical Sciences, Bogor Agricultural University (IPB University), under approval number 130/KEH/SKE/V/2019.

Results

Insertion and retention of the IVD

The insertion of the IVD into the vaginal lumen was successful in all five cats. Radiographic imaging of the cat’s vaginal lumen was performed before and after IVD insertion. Radiographic imaging confirmed the correct placement of the IVD before and after insertion. For the first cat, radiographs were taken up to seven days post-insertion, while for cats 2, 3, 4, and 5, imaging was performed before (H0) and immediately after insertion (H1) (Fig. 4). The IVD in the first cat remained in place until between the third and seventh days post-insertion, while in the other cats, the IVDs were expelled by the second day. RFID readers successfully identified the RFID chips in all cats. Figure 4 shows the radiographic appearance of the cat’s reproductive tract before and after insertion of the IVD, indicating that the IVD (marked with a black star) is in the vaginal lumen.

Fig. 4. The radiographic appearance of the cat's reproductive tract before and after insertion of the IVD, it can be seen that the IVD (black star) is in the vaginal lumen. Day 0 before IVD insertion image in ventrodorsal position of (a) 1st cat, (i) 2nd cat, (m) 3rd cat, (q) 4th cat, and (u) 5th cat. Day 0 before IVD insertion image in laterolateral position of (e) 1st cat, (k) 2nd cat, (o) 3rd cat, (s) 4th cat, and (w) 5th cat. Day 1 after IVD insertion image in ventrodorsal position of (b) 1st cat, (j) 2nd cat, (n) 3rd cat, (r) 4th cat, and (v) 5th cat. Day 1 after IVD insertion image in laterolateral position of (f) 1st cat, (l) 2nd cat, (p) 3rd cat, (t) 4th cat, and (x) 5th cat. Day 3 after IVD insertion image in ventrodorsal position (c) and laterolateral (g) of 1st cat. Day 7 after IVD insertion image in ventrodorsal position (d) and laterolateral (h) of 1st cat.

Fig. 4.

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Hematological analysis

The hematological profile of cats before and after IVD insertion is presented in Table 1. Most hematological parameters were within the normal range before and after IVD insertion, except for erythrocytes, hemoglobin, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). The total number of erythrocytes and hemoglobin levels were below normal values before insertion and decreased further after insertion. MCV and MCH values were above normal before insertion and decreased post-insertion. The total number of neutrophils, lymphocytes, monocytes, and eosinophils increased post-insertion but remained within normal ranges. The neutrophil to lymphocyte (N/L) ratio was above normal before insertion and decreased post-insertion. Overall, there were no significant differences in hematological parameters before and after IVD insertion (p > 0.05).

Table 1. Hematological profile of cats before and after IVD insertion.

Parameter Normal Valueǂ Day 0, n=5 Day 1, n=5 Day 3†, n=1 p value
Erythrocytes (x 106/μl) 7.00–10.70 4.50 ± 0.93 4.18 ± 0.74 3.50 0.564
Hemoglobin (g/dl) 11.30–15.50 13.64 ± 2.75 12.24 ± 2.04 11.20 0.387
Hematocrit (%) 33.00–45.00 41.00 ± 8.22 37.40 ± 5.86 34.00 0.448
MCV (fl) 41.00–49.00 91.11 ± 1.22 89.74 ± 3.56 97.14 0.410
MCH (pg) 14.00–17.00 30.33 ± 0.21 29.36 ± 1.67 32.00 0.229
MCHC (%) 3.00–36.00 30.06 ± 0.32 30.60 ± 1.05 30.36 0.306
Leukocytes (x 103/μl) 4.60–12.80 9.42 ± 1.40 11.10 ± 3.89 11.80 0.390
Neutrophils (x 103/μl) 2.32–10.01 6.82 ± 1.56 7.51 ± 2.93 7.67 0.656
Lymphocytes (x 103/μl) 1.05–6.00 2.11 ± 0.84 3.06 ± 1.29 3.13 0.202
Monocytes (x 103/μl) 0.50–0.68 0.37 ± 0.11 0.52 ± 0.32 0.47 0.336
Eosinophils (x 103/μl) 0.10–0.60 0.14 ± 0.06 0.21 ± 0.08 0.35 0.247
Basophils (x 103/μl) 0.00–1.50 0.05 ± 0.02 0.10 ± 0.00 0.17 0.538
N/L ratio 1.66–2.20 3.24 ± 2.44 2.45 ± 1.42 2.45 0.356
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Data are presented as mean ± standard deviation (x ± SD). The value (p < 0.05) shows a significant difference between the days before and after IVD insertion. Day 0 = Day before IVD insertion and before estrogen injection, day 1 = Day 1 after IVD insertion, Day 3 = Day 3 after IVD insertion. † = Not included in the test, because n = 1; MCV = Mean Corpuscular Volume; MCH = Mean Corpuscular Hemoglobin; MCHC = Mean Corpuscular Hemoglobin Concentration; N/L = Ratio of the number of neutrophils compared to lymphocytes. Source: ǂ (Wassmuth et al., 2011).

Vulva observation

Figure 5 shows the vulva of the cats before and after IVD insertion. Visual inspection of the vulva in all five cats indicated that prior to IVD insertion, the vulva was rose-colored with no mucus discharge. Post-insertion observations showed clear mucus discharge and redness, with no signs of purulent exudate or significant inflammation.

Fig. 5. The appearance of the cat's vulva before IVD insertion was rose-colored with no mucus discharge (a–e), and showed clear mucus discharge and redness, with no signs of purulent exudate or significant inflammation after IVD insertion (f–j).

Fig. 5.

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Vaginal cytology

Morphological examination of epithelial cells in cat vaginal smears were conducted on days 0, 1, 3, and 7 after IVD insertion (Fig. 6). Cats were injected with estrogen three hours before IVD insertion. The ovarian activity phase before estrogen injection was in the proestrus phase (1st, 3rd, 4th, and 5th cats), characterized by a dominant number of intermediate cells, and in the estrus phase (2nd cat), characterized by a dominant number of superficial cells (Table 2). Vaginal cytology profiles before and after IVD insertion are presented in Table 2. Cytological examination revealed a shift from proestrus to estrus phases in all cats following estrogen injection. Significant decreases (p < 0.05) in parabasal and intermediate cell counts were observed post-insertion, with a corresponding increase in superficial cells and neutrophils, indicating an estrogen-induced estrus phase. Only one cat showed neutrophil infiltration indicative of inflammation, while the others did not exhibit inflammatory responses (Table 3).

Fig. 6. The appearance of the epithelial cell of vagina before and after estrogen (E2) injection and an IV) insertion. Day 0, Before E2 injection of (a) 1st cat, (f) 2nd cat, (j) 3rd cat, (n) 4th cat, and (r) 5th cat. Day 0, after E2 injection of (b) 1st cat, (g) 2nd cat, (k) 3rd cat, (o) 4th cat, and (s) 5th cat. Day 1 after IVD insertion of (c) 1st cat, (h) 2nd cat, (l) 3rd cat, (p) 4th cat, and (t) 5th cat. Day 3 after IVD insertion of (d) 1st cat, (i) 2nd cat, (m) 3rd cat, and (q) 4th cat. Day 7 after IVD insertion of 1st cat (e). Note: ǂ = vaginal smear slides were not readable, † = vaginal smear was not taken due to the inserted IVD expelled.

Fig. 6.

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Table 2. Epithelial cell profiles in individual cat vaginal smears before and after IVD insertion.

Cel type (%) Cat #1 Cat #2 Cat #3 Cat #4 Cat #5
Day 0 before estrogen (E2) injection
Parabasal 9.53 ± 4.49 6.21 ± 6.98 3.43 ± 1.36 9.86 ± 8.27 4.38 ± 2.52
Intermediate 60.04 ± 16.70 31.05 ± 9.35 65.09 ± 17.98 55.21 ± 26.03 56.97 ± 14.06
Superficial 30.43 ± 12.61 62.74 ± 16.26 31.49 ± 10.38 34.93 ± 15.31 38.65 ± 14.90
Neutrophil 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00
Total 100.00 100.00 100.00 100.00 100.00
Estrus phase Proestrus Estrus Proestrus Proestrus Proestrus
Day 0 after estrogen (E2) injection
Parabasal 1.03 ± 0.66 5.99 ± 5.85 5.04 ± 3.93 1.65 ± 0.93 0.00 ± 0.00
Intermediate 12.71 ± 5.47 20.06 ± 3.47 28.10 ± 15.92 28.84 ± 15.72 1.14 ± 0.66
Superficial 86.26 ± 14.72 78.16 ± 29.46 66.86 ± 18.43 69.50 ± 10.10 98.86 ± 21.40
Neutrophil 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00
Total 100.00 100.00 100.00 100.00 100.00
Estrus phase Estrus Estrus Estrus Estrus Estrus
Day 1 after IVD insertion
Parabasal 0.00 ± 0.00 4.43 ± 5.68 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00
Intermediate 1.37 ± 0.98 22.57 ± 29.57 4.57 ± 3.04 10.01 ± 7.98 0.00 ± 0.00
Superficial 1.66 ± 0.53 71.97 ± 31.55 95.43 ± 27.31 89.99 ± 33.82 100.00 ± 39.17
Neutrophil 96.96 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00
Total 100.00 100.00 100.00 100.00 100.00
Estrus phase Estrus Estrus Estrus Estrus Estrus
Day 3 after IVD insertion
Parabasal 0.12 ± 0.10 1.26 ± 2.90 0.00 ± 0.00 0.00 ± 0.00 ǂ
Intermediate 1.95 ± 0.92 8.37 ± 2.96 6.67 ± 3.98 10.44 ± 5.25 ǂ
Superficial 0.50 ± 0.21 90.38 ± 26.26 93.33 ± 16.15 89.56 ± 31.07 ǂ
Neutrophil 97.43 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 ǂ
Total 100.00 100.00 100.00 100.00
Estrus phase Estrus Estrus Estrus Estrus
Day 7 after IVD insertion
Parabasal 0.00 ± 0.00 † † † †
Intermediate 40.08 ± 0.00 † † † †
Superficial 59.92 ± 0.00 † † † †
Neutrophil 0.00 ± 0.00 † † † †
Total 100.00
Estrus phase Estrus
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Data are presented as mean ± standard deviation (x ± SD). ǂ = the vaginal smear was not readable, † = the vaginal smear was not taken because the IVD was expelled.

Table 3. Epithelial cell profile in feline vaginal smears before and after IVD insertion.

Cell type (%) Day 0, before E2 injection, n=5 Day 0, after E2 injection, n=5 Day 1, after IVD insertion, n=5 Day 3, after IVD insertion, n=4 Day 7, after IVD insertion†, n=1 p value
Parabasal 7.26 ± 3.04b 2.05 ± 1.76 a 1.09 ± 0.00 a 0.34 ± 0.61a 0.00 ± 0.00 0.009
Intermediate 53.67 ± 13.19b 18.55 ± 10.59 a 7.70 ± 8.02 a 6.86 ± 3.62a 40.08 ± 0.00 0.031
Superficial 39.65 ± 13.30a 79.93 ± 13.05b 71.81 ± 40.63b 68.44 ± 45.32b 59.92 ± 0.00 0.019
Neutrophil ǂ 0.00 ± 0.00 0.00 ± 0.00 96.96 ± 0.00 97.43 ± 0.00 0.00 ± 0.00 n.a.
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Data are presented as mean ± standard deviation (x ± SD). Different superscript letters on the same line indicate significant differences (p < 0.05). † = Not included in the test, because n = 1, ǂ = Not included in statistical tests because only one cat responded, n.a.= not available, and E2 = Estrogen.

Discussion

This preliminary research was successfully conducted to assess the potential biocompatibility of an IVD as a combined contraceptive and intravaginal radiofrequency-based identity device for local vaginal and systemic tissue in non-pregnant cats (Fig. 1). The IVD, developed for cats, is made from polyethylene plastic with a copper coil and is equipped with an RFID chip (Fig. 2). The contraceptive device operates by releasing copper ions (Cu), which impair and disrupt the motility of sperm deposited in the vaginal lumen (Manuaba, 2009). To facilitate the insertion process, cats receiving IVD are first injected with estrogen to relax the vaginal muscles by increasing blood supply to the area (Dewi et al., 2011). The RFID chip embedded in the contraceptive device was successfully read by an RFID reader in all five cats, providing data in the form of a serial number from the RFID chip (Fig. 3).

Radiographic examination showed that the IVD was still present in the vaginal lumen of all five cats (Fig. 4). The IVDs in four cats were expelled on the second-day post-insertion, with only one device remaining in place until the fifth-day post-insertion (Fig. 4a–h). The expulsion of the IVD from the cat’s vaginal lumen occurred because the nylon plastic retainer could not hold the IVD in place for an extended period. Volpe et al. (2001) conducted a study in which they installed IUD contraceptives in nine female dogs, and the devices remained in place for two years (three estrous cycles). The IUD contraceptives lasted longer because they had two retaining arms situated in the uterine lumen, which is deeper than the vaginal lumen, and their flexibility helped prevent the contraceptives from moving out of position (Volpe et al., 2001).

The insertion of an IVD into the vaginal lumen has the potential to cause a rejection reaction by the body in the form of inflammation; however, this was not evident in the blood profiles of the cats in this study (Table 1). The immune response begins when the IVD is inserted into the vaginal lumen. Inflammation is a response to harmful stimuli, infection by pathogenic agents, cell damage, or irritation, which causes a complex biological response in the tissue (Nathan, 2002). The local response to IVD insertion was examined by observing the morphological appearance of the vulva (Fig. 5) and through cytological examination of vaginal epithelial cells (Fig. 6). The appearance of the vulvas in the five cats showed no signs of inflammation, as indicated by the absence of purulent exudate. Inflammation of the vagina can be identified by the presence of purulent exudate on the vulva (Nicastro and Walshow, 2007). The vulvas of the five cats appeared swollen with clear mucus discharge (Fig. 5). Changes in the vulva’s condition, such as color, size, and mucus discharge, are related to the hormone estrogen, which increases during estrus. Frandson et al. (2003) stated that estrogen stimulates increased vascularization in the external genitals, making them swollen and reddish, and increases mucus secretion in the vulva.

Cytological examination of vaginal epithelial cells in cats was conducted to determine the presence of inflammation due to IVD insertion (Fig. 6, Tables 2 and 3). Inflammation from IVD insertion was observed in only one cat (20% of the population). Inflammation is characterized by the presence of neutrophil cell infiltration in the vaginal smear examination (Harold, 2002). The inflammatory process results in the migration of various inflammatory cells from the circulatory system to the tissues. The duration and intensity of these responses depends on the area of injury caused by the implant placement, chemical composition of the material, surface shape, porosity, roughness, and the shape and size of the implant (Li et al., 2005).

Systemic biocompatibility of an implant can be determined through hematological examination (Omerkovic et al., 2015). Biocompatibility refers to a material’s ability to function appropriately according to the recipient tissue’s response under specific conditions (Bosco et al., 2012). The erythrocyte index values in cats were not influenced by IVD insertion (Table 1). The decrease in erythrocyte index values in cats could be attributed to the effects of anesthesia before blood sampling. General anesthesia causes dilation of splenic blood vessels and constriction of peripheral blood vessels, resulting in significant blood accumulation in the splenic blood vessels and a consequent decrease in erythrocyte index values (Schaefer, 2022). Estrogen injection did not contribute to the decrease in erythrocyte index values. Estrogen injection stimulates hematopoietic stem cell division and erythropoiesis (Sánchez-Aguilera et al., 2014).

The erythrocyte index value in cats can also indicate the occurrence of normochromic macrocytic anemia from the beginning of the study. Normochromic macrocytic anemia is characterized by erythrocytes that are larger than normal in size, with a normal hemoglobin concentration (normal MCHC) but increased MCV and MCH, which is often caused by a deficiency of vitamin B12 or folic acid (Muttaqin, 2009). This condition is thought to be due to the cats experiencing stress while adapting to a new environment, resulting in impaired vitamin absorption (Hastjarjo et al., 2018). Despite the administration of oral vitamin B-complex during the acclimatization period, the amount provided was insufficient to meet the cats’ needs during the adaptation period.

The research cats used were feral cats that were then kept in cages. At the beginning of the study, the cats’ behavior changed to become more aggressive; they often hid and consumed little food. Turner and Bateson (2014) stated that stressful conditions in cats could cause changes in normal behavior, such as increased aggression, prolonged hiding, reduced exploration, and anorexia. At the start of the study, the cats were fed with a mixture of wet and dry food three times a day, and drinking water was provided ad libitum. The cats were also given vitamin B complex to reduce stress levels. McDowell (2000) stated that administering vitamin B complex can alleviate stress. Over time, stress was decreased, as indicated by reduced aggressive behavior and increased food consumption, suggesting that the cats were beginning to adapt to their new environment.

Leukocytes play a crucial role in the body’s immune system, defending against infectious agents and foreign objects (Keohane et al., 2015). The number of leukocytes in the cats’ blood was not significantly affected by the insertion of the IVD into the vagina, remaining within the normal range even though there was a slight increase post-insertion. Lymphocytes and neutrophils are key defense cells involved in the inflammatory response. Neutrophils are the first line of defense against bacterial infections and tissue trauma, commonly appearing at the onset of acute inflammation and playing a role in the phagocytosis of microorganisms, particularly bacteria (Paramitha et al., 2013). Lymphocytes, along with neutrophils in the inflammatory process, also contribute to the body’s defense mechanisms (Izzaty et al., 2014). The insertion of an IVD in the vagina affected the neutrophil response in cats, causing a slight increase post-insertion, but it remained within the normal range (Table 1). Park and Hyun (2016) stated that the number of neutrophils increases due to the inflammatory process. This increase in neutrophils is a normal response to the presence of the IVD, which the body recognizes as a foreign object.

Monocytes are a type of leukocyte that plays a role in both acute and chronic inflammatory processes. Monocytes migrate into inflamed tissue along with neutrophils, although in smaller numbers (Subowo, 2009). Upon tissue damage caused by the IVD insertion, monocytes are rapidly recruited to the site, where they can differentiate into macrophages or dendritic cells and phagocytose the damages tissue. Eosinophils are another type of leukocyte involved in regulating acute allergies, parasitic infections, and inflammatory processes. The production of eosinophils increases during infections and allergic reactions. Eosinophils, basophils, and mast cells are responsible for releasing inflammatory mediators (Behm and Ovington, 2000). Basophils are involved in allergic and antigen responses by releasing histamine, which causes blood vessel dilation during allergic reactions (Saladin, 2009). The insertion of the IVD did not significantly affect the responses of eosinophils and basophils; although there was a slight increase, the levels remained within the normal range (Table 1). The neutrophil-to-lymphocyte (N/L) ratio in cats indicated high-stress levels at the beginning of the study, which decreased after the insertion of the IVD. This change in stress levels is likely due to the cats adapting to their new cage and environment (Table 1).

According to Roy et al. (2014), spermatozoa forward motility is significantly enhanced by the presence of copper ions (Cu2+) in a dose-dependent manner. However, when spermatozoa come into contact with a high concentration of Cu2+ exceeding 5 µM inside the vaginal lumen, their motility is significantly reduced. This clear evidence suggests that sperm motility is regulated by Cu2+. Furthermore, sperm head-to-head agglutination occurs when the concentration of Cu2+ exceeds 100 μM, causing oxidative stress and leading to spermatozoa toxicity. The abundant amount of Cu2+ prevents fertilization by inhibiting spermatozoa migration and viability. Therefore, by halting sperm motility and preventing them from reaching the ovum, the copper IUD functions as an emergency contraceptive method (Roy et al., 2014; Ramanadhan et al., 2023). Figure 7 illustrates the mechanism of toxicity caused by Cu ions in the vaginal lumen.

Fig. 7. The mechanism of spermatozoa toxicity caused by Cu ions inside the vaginal lumen. It shows that if the concentration of Cu ions are above 100 μM, the spermatozoa will start to form head-to-head agglutination, whereas, if the concentration of Cu ions are above 5 μM, the spermatozoa motility will be significantly reduced.

Fig. 7.

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Conclusion

The initial testing of the developed IVD indicated that it holds a good potential as a biocompatible contraceptive and identity device for cats. The IVD was generally well-tolerated, with no significant adverse local or systemic reactions observed during the short-term evaluation period. However, the retention of the device was limited, as four out of five cats expelled the IVD by the second-day post-insertion. Only one cat retained the IVD for up to seven days. Further research needs to be done regarding the design of the IVD so that the duration of the IVD in the vaginal lumen can last longer, as well as attempts at conception failure by mating cats that have had the IVD inserted with male cats.

Limitations

This preliminary study indicated that the integrated contraceptive and intravaginal radiofrequency-based identity device (IVD) is generally well-tolerated in female cats, with no significant adverse reactions observed in the short term. However, the study had a small sample size of only five cats and a short duration of seven days post-insertion, limiting the generalizability and long-term assessment of biocompatibility and contraceptive efficacy.

Future research should include a larger sample size and more extended monitoring periods to provide more comprehensive data. Additionally, device design improvements, such as using materials with lower tissue reactivity and refining the insertion procedure for better stability, are recommended. Long-term studies and mating trials are necessary to evaluate the IVD’s effectiveness in preventing pregnancies and its impact on the overall health and behavior of the cats.

Overall, while the study provides promising preliminary evidence for the IVD’s potential as a contraceptive and identity device for felines, addressing these limitations and conducting further research is crucial to confirming its utility and safety for widespread use.

Acknowledgment

The authors would like to thank the Directorate of Research and Innovation of IPB University for the Riset Kolaborasi Nasional Grant that supports this project.

Funding

This research was funded by Dana Abadi Perguruan Tinggi-Lembaga Pengelola Dana Pendidikan (DAPT-LPDP) through International Research Collaboration Funding Program (Riset Kolaborasi Internasional) with the Grant No. 571/IT3.D10/PT.01.03/P/B/2023.

Authors’ contribution

MFU: Conceptualization, methodology; MIBS, SSA, DU, FAA, RP, YA: Data curation, writing-original draft preparation; MIBS, SSA, DU, FAA, RP, YA: Visualization, investigation; MFU, G: Supervision; MFU: Validation; MIBS, MFU, MNS, AHY: Writing-reviewing and editing.

Conflicts of interest

The authors have no conflicts of interest to declare.

Data availability

Some of the data supporting we used in this paper are obtained from MIBS Undergraduate Thesis during his study in the School of Veterinary Medicine and Biomedical Sciences, Bogor Agricultural University (IPB University), MIBS is an author of this paper. Thesis data are deposited in the Bogor Agricultural University repository and are free-accessed online through http://repository.ipb.ac.id/handle/123456789/105279.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Some of the data supporting we used in this paper are obtained from MIBS Undergraduate Thesis during his study in the School of Veterinary Medicine and Biomedical Sciences, Bogor Agricultural University (IPB University), MIBS is an author of this paper. Thesis data are deposited in the Bogor Agricultural University repository and are free-accessed online through http://repository.ipb.ac.id/handle/123456789/105279.

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