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Calophyllum inophyllum L is a plant found on the coast and is known to have pharmacological effects such as anti-oxidant, anti-cancer, anti-viral and anti-inflammatory. This study aimed to determine the ability of the ethanolic extract of the sampling seed shells as a spermicide for albino mice (Mus musculus), determine the growth inhibition of Candida albicans, and identify its compounds. The extraction of the C. inophyllum L seed shell was carried out by maceration. The quality of motility and abnormal morphology of mice sperms were observed under the microscope. The fungus inhibition assay was carried out by diffusion agar, and the identification of the active compounds by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC/MS-MS). Sperm motility in ethanolic extract at the concentrations of 0.1, 0.3, and 0.5% were 10.85, 10.05, and 10.85%, respectively, and the abnormal morphology was 63.50, 65.62, and 72.67%, respectively. The partition results of the n-hexane extract showed that motility and abnormal morphology values at the concentrations of 0.1, 0.3, and 0.5% were 79.21 and 79.93%, and the abnormal morphology was 8.49, 4.30 and 0.00%, respectively. Fraction F6 at the concentration of 0.3% showed that its motility was 0.00% and abnormal morphology was 65.86%, so it did not provide inhibition against the C. albicans fungus. Fraction F6 contained compounds that had spermicidal potential were 2,5-Dioxo-1-pyrrolidinyl N-[(benzyloxy) carbonyl]-D-phenylalaninate, raubasine, and N-(4-{[2,4-Diamino-7,8-dyhydro-6 pteridinyl) methyl] (methyl) amino} benzoyl) Lglutamic acid or methotrexate through to cytotoxic effects. [ABSTRACT FROM AUTHOR]

This study aimed to determine the spermicidal activity of papaya seed oil (Carica papaya L) from local Bali varieties against Wistar rat spermatozoa by evaluating sperm quality and the correlation between the percentage of motility and viability spermatozoa to identify its active compounds. Papaya seed oil was obtained by extracting papaya seeds using n-hexane solvent. The study was designed as follows; group of spermatozoa Wistar rat were treated with NaCl 0.9% (control, P0), with Sodium carboxy methyl cellulose (NaCMC) 0.5% (P1), with n-hexane extract 0.1%(b/v) (P2), with n-hexane extract 0.3%(b/v) (P3), and with n-hexane extract 0.5%(b/v) (P4). Column chromatography was used to separate the n-hexane extract into two fractions, A and B. The spermicide test for fractions A and B followed the same design as the test for n-hexane extract but until the P7 group. The result showed that fraction B exhibited higher spermicidal activity, with 23.3% motility and 33.8% of viability sperm at 100 ppm. The identification of fraction B by LCMS showed at least 12 mixture compounds were venoterpine, vitamin K5, 5-phenyl-2-pyridinamine, harmalan, styrylquinoline, 1,2,3,4-tetrahydro-1-benzoyl-2-methyl-4-phenylamino-quinoline, calcitroic acid, siderol, N-benzyl-linoleamide, (3β)-3-(diisopropylamino)androst-5-en-17-one, pipereicosalidine, and 25-azacholesterol. Spermicidal activity may be a synergistic effect of several compounds that have a cytotoxic activity such as styrylquinoline, 1,2,3,4-tetrahydro-1-benzoyl-2-methyl-4-phenylamino-quinoline, siderol, and pipereicosalidine. [ABSTRACT FROM AUTHOR]

It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X1), terpenes concentration (X2), terpenes type (X3), and chitosan concentration (X4) as independent variables, while their impact was observed for entrapment efficiency percent (Y1; EE%), particle size (Y2; PS), zeta potential (Y3; ZP), and amount of drug released after 6 h (Y4; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for ex-vivo and in-vivo investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive.

This study aimed to (1) provide a comprehensive overview of contraceptive methods self-reported by men in England, over 5 years, focusing on condoms in comparison to any male method; and (2) explore condom as a contraceptive method by region and ethnicity. Data were from the Sexual and Reproductive Health Services (Contraception) England census data set from 2014/15 to 2018/19. Once missing data were removed, this left a total of 365,292 men. Two binomial logistic regression models were performed. Model 1 examined ethnicity, region, and time on condom as a method of contraception; and Model 2 examined ethnicity, region, and time by any male contraceptive. Descriptive statistics were run for natural family planning and spermicide. Model 1 revealed a significant model, χ2 (15) = 30,976, P < 0.001, and predicted that condoms as a method decreased in London with a greater decrease in Midlands. London saw the lowest rate of decline among the non-White ethnic group, whereas North and South regions increased probability over time. The North started at a higher probability and the South at the lowest. Model 2 also revealed a significant model, χ2 (15) = 32,472, P < 0.001, with a similar pattern to Model 1. Contingency tables showed natural family planning and spermicide were the least reported methods and decreased over time. As any male contraceptive method appears to be decreasing in both models, reproductive health promotion is required. This study has implications for commissioning funds and for identifying regional areas of further investigation. [ABSTRACT FROM AUTHOR]

It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X1), terpenes concentration (X2), terpenes type (X3), and chitosan concentration (X4) as independent variables, while their impact was observed for entrapment efficiency percent (Y1; EE%), particle size (Y2; PS), zeta potential (Y3; ZP), and amount of drug released after 6 h (Y4; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for ex-vivo and in-vivo investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive. [ABSTRACT FROM AUTHOR]

Study Question: Is 17BIPHE2, an engineered cathelicidin antimicrobial peptide with low susceptibility to proteases, a better spermicide in cervicovaginal fluid (CVF) than its parental peptides, LL-37 and GF-17?Summary Answer: At the same mass concentration, 17BIPHE2 exhibited the highest spermicidal activity on human sperm resuspended in CVF-containing medium.What Is Known Already: LL-37 and its truncated peptide GF-17 exert both spermicidal and microbicidal activities, although they are prone to proteolytic degradation in body fluids.Study Design, Size, Duration: Spermicidal activities of 17BIPHE2 were evaluated in vitro in mouse and human sperm, both resuspended in medium, and then on human sperm incubated in CVF-containing medium; in the latter condition, the spermicidal activity and peptide stability in CVF of 17BIPHE2 were compared with that of LL-37 and GF-17. The in vivo contraceptive effects of 17BIPHE2 and the reversibility thereof were then assessed in mice. Finally, in vitro microbicidal effects of 17BIPHE2 on Neisseria gonorrhoeae were determined.Participants/materials, Setting, Methods: Sperm motility and plasma membrane integrity were assessed by videomicroscopy and exclusion of Sytox Green, a membrane-impermeable fluorescent dye, respectively. Successful in vitro fertilization (IVF) was determined by the presence of two pronuclei in oocytes following their coincubation with capacitated untreated or 17BIPHE2-treated sperm. Sperm alone or with 17BIPHE2 were transcervically injected into female mice and successful in vivo fertilization was indicated by the formation of two-cell embryos 42-h postinjection, and by pregnancy through pup delivery 21-25 days afterwards. Peptide intactness was assessed by immunoblotting and HPLC. Reversibility of the contraceptive effects of 17BIPHE2 was evaluated by resumption of pregnancy of the female mice, pretranscervically injected with 17BIPHE2, following natural mating with fertile males. Minimum inhibitory/bactericidal concentrations of 17BIPHE2 on N. gonorrhoeae were obtained through microdilution broth assay.Main Results and the Role Of Chance: At the same mass concentration, 17BIPHE2 was a more effective spermicide than LL-37 or GF-17 on human sperm resuspended in CVF-containing medium, with the spermicidal concentration of 32.4 µM. This was mainly due to lower susceptibility of 17BIPHE2 to CVF proteases. Importantly, the reproductive tract of mouse females treated three times with 32.4 µM 17BIPHE2 remained normal and their fecundity resumed after stopping 17BIPHE2 treatment.Limitations, Reasons For Caution: For ethical reasons, the inhibitory effects of 17BIPHE2 on fertilization and pregnancy cannot presently be performed in women. Also, while our study has proven the effectiveness of 17BIPHE2 as a spermicide for mouse and human sperm in vitro, dosage formulation (e.g. in hydrogel) of 17BIPHE2 still needs to be developed to allow 17BIPHE2 to remain in the vagina/uterine cavity with controlled release for its spermicidal action.Wider Implications Of the Findings: Since 17BIPHE2 also exerted bactericidal activity against N. gonorrhoeae at its spermicidal concentration, it is a promising candidate to be developed into a vaginal multipurpose prevention technology agent, thus empowering women against unplanned pregnancies and sexually transmitted infections.Study Funding/competing Interest(s): This work was supported by the Canadian Institutes of Health Research (PJT 173268 to N.T.). There are no competing interests to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Objective: To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions. Methods: A systematic review and meta-analysis aiming to evaluate the spermicidal activity of N-9 on motility, was conducted in PubMed, EMBASE, and Cochrane databases by 10 March 2021. The counted numbers of progressive motile (PR) sperm in cervical mucus and the vanguard sperm penetration distances were analyzed. Other effects on sperm structures and physiological activities were reviewed as well. Results: In the pooled results, percentages or counted numbers of PR sperm decreased after the treatment of N-9. Vanguard sperm penetration distance was shortened in treated groups. N-9 has been confirmed to damage the structures of sperm, as well as other organelles like acrosome and mitochondria. The physiological activities such as generation of reactive oxygen species, superoxide dismutase activity, acrosin activity, and hemizona binding were all inhibited in the reviewed studies. Conclusions: N-9 has several impacts on sperm owing to its potency in reducing sperm motility and cervical mucus penetration, as well as other functional competencies.

Doryopteris raddiana (Presl) Fée, a traditional contraceptive in Mbya culture, lacks scientific scrutiny regarding its chemical composition and contraceptive efficacy. Employing X-ray fluorescence, Fourier-transform infrared spectroscopy, and thermal analysis, we explored the plant's organs. Multielemental analysis excluded toxic elements. Key phytoconstituents identified by gas chromatography-mass spectrometry in the extracts obtained through infusion were glycerine, 1,3-dimethyl propane, and catechol in leaves; glycerine, cis-13-octadecenoic acid methyl ester, and 2-deoxy-D-erythro-pentose in stems and roots. Among these chemicals, glycerine emerged as the sole constituent with contraceptive potential, particularly intravaginally. Extract activity tests conducted on ram spermatozoa exhibited a reduction in the percentage of rapid spermatozoa but no significant impact on total motility, progressive motility, or viability. The reported data would only weakly support the advocated contraceptive action of this fern upon vaginal application, not through the oral administration of its decoction.

Staphylococcus warneri, isolated from the cervix of an adult female with unexplained infertility, was found to agglutinate human spermatozoa in vitro leading to their death. A genomic library of S. warneri was generated using pSMART-Escherichia coli vector-host system. Approximately 3500 transformants were screened and four showed sperm agglutinating activity. Sperm agglutinating proteins (SAPs) were partially purified from the positive transformants and were found to agglutinate sperms in vitro. Cloned ORFs in positive transformants were sequenced and ORF finder identified them as endonuclease, accessory secretory protein-Asp1, accessory secretory protein-Asp2 and signal transduction protein. Mannose was found to competitively inhibit sperm agglutination, indicating that SAPs in S. warneri bind to mannose in glycoprotein receptors on the surface of sperms for agglutination. This is the first report on identification of SAPs which may be responsible for unexplained infertility in women and may be used as contraceptive agents. [ABSTRACT FROM AUTHOR]

DNA evidence in sexual assault cases have proven increasingly difficult to obtain and analyse due to increased condom use. With more interest in alternatives to DNA evidence, prophylactic lubricants, spermicides and residues may be interesting prospects. Current interest in the analysis of prophylactic residues focuses on the evaluation and identification of lubricants and constituents, primarily through gas chromatography or Fourier transform infrared spectroscopy. Though cost-effective methods, extensive sample preparation and destructive modes of analysis remain an area for improvement. As a result, the focus has since shifted to ambient ionization methods that offer adequate sensitivity and reduced sample preparation. The Liquid Microjunction Surface Sampling Probe (LMJSSP) is a versatile ambient ionization source that employs a probe that supports a continuously flushing droplet that extracts analytes when placed in contact with a surface. The analytes are aspirated into the mass spectrometer with a Venturi pressure. In this work we use the LMJSSP to analyse the trace transfer of condom lubricant to different types of fabric (cotton, cotton-spandex, and denim). Furthermore, we examine the sensitivity and storage conditions for the direct analysis method on different swab types (cotton, silicone, and foam). Additionally, Principal Component Analysis (PCA) and Maximally Collapsing Metric Learning (MCML) are utilized for visualization of differentiability of commercially available condom brands including Durex™ and Trojan™, and product subtypes. The results present an interesting multi-disciplinary approach of using a direct liquid extraction ambient ionization technique and machine learning to improve the overall workflow for the analysis of lubricants, swabs and fabrics. Machine learning algorithms were able to differentiate between inherent differences of Durex™ and Trojan™ condoms. [Display omitted] • Ambient ionization is a viable alternative method to standard workflows. • Liquid Microjunction Surface Sampling Probe (LMJSSP) for rapid analysis of lubricants on substrates (swabs, fabrics). • Condom brands were differentiable using machine learning (Principal Component Analysis and Maximally Collapsing Metric Learning). • m/z peaks of interest were identified from condoms with advertised additives (i.e., flavours) from different brands using machine learning. [ABSTRACT FROM AUTHOR]

Objective: To express recombinant protein that comprises an important fragment of human sperm specific voltage dependent anion channel 3 (VDAC3) protein as a potential molecule for generation of antibody, which can affect sperm function, aiming at spermicide development.Methods: The produce of VDAC3 recombinant protein encoded by cDNA sequence of human VDAC3 exon 5-8, based on experimental design of VDAC3 knock-out mice study. And after the purification of various human sperm VDAC3 recombinant proteins, epitope has been predicted in our recombinant protein determined by ElliPro program. Polyclonal antibody was produced for 14 wk. Then anti-VDAC3-exon 5-8 recombinant antiserum was inoculated to human sperm. After the process, antibody VDAC3 protein in human sperm was incubation with anti-VDAC3 recombinant antibody. Finally evaluation the effect of VDAC3 antiserum to human sperm motility and plasma membrane integrity was proceeded.Results: Human VDAC3 recombinant protein was successfully over-expressed in Escherichia coli and purified by affinity chromatography method. Purified human sperm VDAC3 recombinant protein could stimulate immune response in rabbit producing an antibody against VDAC3. Anti-VDAC3 recombinant antibody recognized VDAC3 antigen in human sperm could decrease human sperm motility and membrane integrity significantly.Conclusions: Anti-VDAC3 recombinant polyclonal antibody that we produced in rabbit by ourselves could decrease sperm motility and sperm membrane integrity. The authors suggest this polyclonal antibody could be used as a candidate agent for male contraception in the future. Furthermore, the authors intend to explore the effect of this antibody into sperm function aiming at male contraceptive vaccine development.

Study Question: Do the truncated LL-37 peptides, GI-20 and GF-17, have spermicidal activity and microbicidal effects on the sexually transmitted infection (STI) pathogen Neisseria gonorrhoeae with equivalent potency to LL-37?Summary Answer: GI-20 and GF-17 exhibited spermicidal effects on both mouse and human sperm as well as microbicidal action on N. gonorrhoeae with the same efficacy as LL-37.What Is Known Already: The antimicrobial peptide LL-37 exerts microbicidal activity against various STI pathogens as well as spermicidal effects on both mouse and human sperm.Study Design, Size, Duration: Spermicidal activities of GI-20 and GF-17 were evaluated in vitro in mouse and human sperm and in vivo in mice. Finally, in vitro antimicrobial effects of LL-37, GI-20 and GF-17 on an STI pathogen, N. gonorrhoeae were determined. All experiments were repeated three times or more. In particular, sperm samples from different males were used on each experimental day.Participants/materials, Setting, Methods: The plasma membrane integrity of peptide-treated sperm was assessed by cellular exclusion of Sytox Green, a membrane impermeable fluorescent DNA dye. Successful mouse in vitro fertilization was revealed by the presence of two pronuclei in oocytes following co-incubation with capacitated untreated/peptide-pretreated sperm. Sperm plus each peptide were transcervically injected into female mice and the success of in vivo fertilization was scored by the formation of 2-4 cell embryos 42 h afterward. Reproductive tract tissues of peptide pre-exposed females were then assessed histologically for any damage. Minimal inhibitory/bactericidal concentrations of LL-37, GI-20 and GF-17 on N. gonorrhoeae were determined by a standard method.Main Results and the Role Of Chance: Like LL-37, treatment of sperm with GI-20 and GF-17 resulted in dose-dependent increases in sperm plasma membrane permeabilization, reaching the maximum at 18 and 3.6 μM for human and mouse sperm, respectively (P < 0.0001, as compared with untreated sperm). Mouse sperm treated with 3.6 μM GI-20 or GF-17 did not fertilize oocytes either in vitro or in vivo. Moreover, reproductive tract tissues of female mice pre-exposed to 3.6 μM GI-20 or GF-17 remained intact with no lesions, erosions or ulcerations. At 1.8-7.2 μM, LL-37, GI-20 and GF-17 exerted bactericidal effects on N. gonorrhoeae.Large Scale Data: N/A.Limitations, Reasons For Caution: Direct demonstration of the inhibitory effects of GI-20 and GF-17 on human in vitro and in vivo fertilization cannot be performed due to ethical issues.Wider Implications Of the Findings: Like LL-37, GI-20 and GF-17 acted as spermicides and microbicides against N. gonorrhoeae, without adverse effects on female reproductive tissues. With lower synthesis costs, GI-20 and GF-17 are attractive peptides for further development into vaginal spermicides/microbicides.Study Funding/competing Interest(s): This work was supported by Canadian Institutes of Health Research (MOP119438 and CCI82413 to N.T.) and NIH (R01 AI105147 to G.W.). There are no competing interests to declare. [ABSTRACT FROM AUTHOR]

B07 is a small-molecule CCR5 antagonist-based HIV-1 entry inhibitor that is being developed as an anti-HIV microbicide for preventing sexual transmission of HIV. Here we evaluated its spermicidal and contraceptive potential, including sperm motility, plasma membrane integrity, and contraceptive efficacy tested in rabbits. We found that B07 inhibited sperm motility and movement patterns in a concentration- and time-dependent manner. Within 30 min, B07 induced sperm immobilization with the minimum 100% effective concentration and median effective concentration of 640.0 and 64.4 μg/mL, respectively. The hypo-osmotic swelling test showed that plasma membranes of B07-treated sperms exhibited slight disruption, as verified by electron micrographs. In both B07 gel and N-9 gel groups, not a single implantation site or embryo was observed based on the contraceptive efficacy test in rabbits, indicating that B07 could effectively block the potential of sperm to reach and/or fertilize oocytes. The safety profile of B07 in vivo was evaluated by use of an optimized rabbit vaginal irritation test. While the pathological scores of the N-9 gel group was 14.67 ± 1.21, those of the blank control and B07 gel groups were 2.17 ± 0.76 and 4.00 ± 0.89, respectively, which were within the clinically acceptable range (<8). The proportion of inflammatory cells and CD45 + cells in the cervicovaginal lavages of the B07 gel group showed no significant change compared to those of the control group. Therefore, our results confirmed that B07 exhibited significant spermicidal and contraceptive effects, suggesting its potential for development as a microbicidal spermicide for contraception and prevention of HIV sexual transmission. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to evaluate the effects of ozonised olive oil (OOO) on human sperm in vitro.Methods: Human sperm was incubated with OOO for 20 s in vitro. The lowest concentration that completely immobilised all the sperm in 20 s without subsequent recovery of motility was recorded as the minimum effective concentration (MEC). The effects of OOO at MEC on human sperm viability, mitochondrial and acrosomal status, DNA integrity and transmission electron microscopy were observed.Results: Our findings demonstrate that OOO dose-dependently inhibits sperm motility. The MEC of OOO for 100% sperm immobilisation in 20 s was 6 μg/ml. Further experiments showed that sperm ultrastructure, function and DNA integrity were significantly affected after treatment with 6 μg/ml OOO in vitro.Conclusions: OOO has spermicidal potential and may be explored as a promising vaginal contraceptive agent. [ABSTRACT FROM AUTHOR]

Presently available contraceptives are mostly hormonal or detergent in nature with numerous side effects like irritation, lesion, inflammation in vagina, alteration of body homeostasis, etc. Antimicrobial peptides with spermicidal activity but without adverse effects may be suitable alternatives. In the present study, spermicidal activity of a cationic antimicrobial peptide VRP on human spermatozoa has been elucidated. Progressive forward motility of human spermatozoa was instantly stopped after 100 µM VRP treatment and at 350 µM, all kinds of sperm motility ceased within 20 s as assessed by the Sander-Cramer assay. The spermicidal effect was confirmed by eosin-nigrosin assay and HOS test. VRP treatment (100 µM) in human spermatozoa induced both the intrinsic and extrinsic pathways of apoptosis. TUNEL assay showed VRP treatment significantly disrupted the DNA integrity and changed the mitochondrial membrane permeability as evident from MPTP assay. AFM and SEM results depicted ultra structural changes including disruption of the acrosomal cap and plasma membrane of the head and midpiece region after treatment with 350 µM VRP. MTT assay showed after treatments with 100 and 350 µM of VRP for 24 hr, a substantial amount of Lactobacillus acidophilus (about90%and 75%, respectively) remained viable. Hence,VRPbeing a small synthetic peptide with antimicrobial and spermicidal activity but tolerable to normal vaginal microflora, may be a suitable target for elucidating its contraceptive potentiality. [ABSTRACT FROM AUTHOR]

Objective: This multicenter prospective study (BZK40+) aims to determine the efficacy and tolerance of a benzalkonium chloride-containing spermicide as contraceptive among women aged 40 and over., Procedure: Fertile women enrolled in this open single-arm study were instructed to systematically use the benzalkonium chloride spermicide before each intercourse. At the end of a 6-month mandatory period, participants were given the option of continuing the study for a further 6 months. The primary endpoint for contraceptive efficacy was the Pearl Index (PI) up to 12 months of typical use., Main Findings: A total of 151 women (mean age: 45.9 years) were enrolled, 144 (95.4%) completed the initial 6-month period and 63 (41.7%) completed the optional 6-month period. The median number of intercourses ranged from 3 to 5 per month. The spermicide was applied before 96.3% of the 5,895 sexual intercourses. The PI up to 12 months of typical use was 0 pregnancies (95% confidence interval: 0-2.88). The cumulative treatment exposure was 1249.7 women-months., Conclusion: This first study in women aged 40 years and over shows that benzalkonium chloride spermicide (Pharmatex®) is effective, well tolerated and well accepted in this population. Although very interesting, these results with a PI equal to zero are surprising and not in accordance with the low efficacy of spermicides in the overall population according to the WHO. So, our results should be interpreted with caution and confirmed by future research. Clinical trial registration number (EudraCT): 2016-004,188-38., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

We have previously demonstrated spermicidal activity of LL-37 antimicrobial peptide on mouse/human sperm and its contraceptive effects in female mice. With its microbicidal action against Neisseria gonorrhoeae, LL-37 warrants development into a multipurpose prevention technology (MPT) agent for administering into the female reproductive tract (FRT). However, it is important to verify that multiple administrations of LL-37 do not lead to damage of FRT tissues and/or irreversible loss of fecundity. Herein, we transcervically injected LL-37 (36 µM-10× spermicidal dose) into female mice in estrus in three consecutive estrous cycles. A set of mice were sacrificed for histological assessment of the vagina/cervix/uterus 24 h after the last injection, while the second set were artificially inseminated with sperm from fertile males 1 week afterwards, and then monitored for pregnancy. Mice injected with PBS in parallel were regarded as negative controls, whereas those injected with vaginal contraceptive foam (VCF, available over the counter), containing 12.5% nonoxynol-9, served as positive controls for vaginal epithelium disruption. We demonstrated that the vagina/cervix/uterus remained normal in both LL-37-injected and PBS-injected mice, which also showed 100% resumption of fecundity. In contrast, VCF-injected mice showed histological abnormalities in the vagina/cervix/uterus and only 50% of them resumed fecundity. Similarly, LL-37 multiply administered intravaginally caused no damage to FRT tissues. While our results indicate the safety of multiple treatments of LL-37 in the mouse model, similar studies have to be conducted in non-human primates and then humans. Regardless, our study provides an experimental model for studying in vivo safety of other vaginal MPT/spermicide candidates., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Trichomoniasis and candidiasis are amongst the most common morbidity-causing reproductive tract infections, generally treated by Metronidazole and Fluconazole respectively. Poor vaginal efficacy, drug-resistance and non-spermicidal nature limit their use as topical microbicidal contraceptives. Bis(dialkylaminethiocarbonyl)disulfides ( 4 – 38 ) were designed as dually active, non-surfactant molecules capable of eliminating Trichomonas vaginalis and Candida strains as well as irreversibly immobilizing 100% human sperm instantly, at doses non-cytotoxic to human cervical epithelial cells and vaginal microflora in vitro . Compounds 12, 16, 17 were fifty times more active than nonoxynol-9, OTC vaginal spermicide, and compounds 12 and 17 have shown remarkable in vivo activity in rabbit model. Most promising compound 17 has shown promise for further development as a double-edged vaginal microbicide due to their improved activity and safety along with notable in vivo trichomonicidal activity. Role of disulfide group was established by loss of spermicidal activity on chemical modifications ( 39 – 56 ). These disulfides might be targeting thiol groups present over cell membrane of human sperm and Trichomonas as shown by fluorescence labeling of free thiols. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility of using quantitative changes in vaginal permeability to small molecules as a measure of candidate microbicide toxicity.Study Design: Controlled, open-labeled, prospective study. Seven healthy women received a single vaginal dose of hydroxyethylcellulose gel (HEC), nonoxynol-9 (N-9) or K-Y Jelly. Each gel was radiolabeled with a small molecule ((99m)Tc-DTPA) followed by 12-h blood and urine collection. Pharmacokinetic (PK) parameters of (99m)Tc-DTPA were calculated to compare the impact of each gel on vaginal permeability. Each woman served as her own control. The Friedman test with post hoc Wilcoxon test was used to detect differences among the gels.Results: Vaginal permeability of (99m)Tc-DTPA was highest for the N-9 radiolabel. N-9 plasma area under the concentration curve was 2.7-fold higher (p=.04), and peak concentration was threefold higher (p=.04) compared to HEC. There were no significant PK parameter differences between HEC and K-Y Jelly or between N-9 and K-Y Jelly. Cumulative dose-adjusted median (interquartile range) 12-h timed urine gamma activity was 66.70 × 10(-4)μCi (27.90-152.00) following HEC dosing, 103.00 × 10(-4)μCi (98.20-684.00) following N-9 gel dosing and 20.30 × 10(-4)μCi (11.10-55.90) following K-Y gel dosing. The differences between urine HEC and K-Y Jelly (p=.047) and between N-9 and K-Y Jelly (p=.016) were statistically significant.Conclusions: It is feasible to measure differences in vaginal permeability among vaginal gels using a radiolabeled small molecule, though there are permeability differences that require a nuanced understanding of gel composition to interpret the results.Implications: Establishing the safety of both vehicle and active pharmaceutical ingredient is an essential task in microbicide development, to be determined as soon as possible. This study suggests that a combination of microbicide toxicity assessments, that is, cervicovaginal permeability, inspection and histopathology, may need to be studied simultaneously. [ABSTRACT FROM AUTHOR]

The concurrent increases in global population and sexually transmitted infection (STI) demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9), into a vaginal microbicide were unsuccessful largely due to its inefficiency to kill microbes. Furthermore, N-9 causes damage to the vaginal epithelium, thus accelerating microbes to enter the women's body. For this reason, antimicrobial peptides (AMPs), naturally secreted by all forms of life as part of innate immunity, deserve evaluation for their potential spermicidal effects. To date, twelve spermicidal AMPs have been described including LL-37, magainin 2 and nisin A. Human cathelicidin LL-37 is the most promising spermicidal AMP to be further developed for vaginal use for the following reasons. First, it is a human AMP naturally produced in the vagina after intercourse. Second, LL-37 exerts microbicidal effects to numerous microbes including those that cause STI. Third, its cytotoxicity is selective to sperm and not to the female reproductive tract. Furthermore, the spermicidal effects of LL-37 have been demonstrated in vivo in mice. Therefore, the availability of LL-37 as a vaginal spermicide/microbicide will empower women for self-protection against unwanted pregnancies and STI. [ABSTRACT FROM AUTHOR]

The growing population and health-care burden (due to STIs and HIV) imposes a particular economic crisis over resource-poor countries. Thus a novel approach as vaginal microbicides emerges as integrated tool to control both population and anti-STIs/HIV. Our continued efforts in this field led to the synthesis of fifteen N-alkyl/aryl-4-(3-substituted-3-phenylpropyl) piperazine-1-carbothioamide ( 12 – 26 ) derivatives as topical vaginal microbicides which were evaluated for anti- Trichomonas , spermicidal, antifungal and reverse transcriptase (RT) inhibitory activities. All compounds were also tested for preliminary safety through cytotoxicity assays against human cervical cell line ( HeLa ) and the vaginal flora, Lactobacillus . Docking studies were performed to gain an insight into the binding mode and interactions of the most promising compound 12 [oxo derivative], comprising of reverse transcriptase (RT) inhibitory (72.30%), spermicidal (MEC 0.01%), anti- Trichomonas (MIC 46.72 μM) and antifungal (MIC 9.34–74.8 μM) activities, along with its hydroxyl ( 17 ) and O-alkylated 4-trifluoromethylphenoxy ( 22 ) derivative, with similar activities. The stability of compound 12 in simulated vaginal fluid (SVF) and its preliminary in vivo pharmacokinetics performed in female NZ -rabbits signifies its clinical safety in comparison to marketed spermicide Nonoxynol-9. [ABSTRACT FROM AUTHOR]

The concurrent increases in global population and sexually transmitted infection (STI) demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9), into a vaginal microbicide were unsuccessful largely due to its inefficiency to kill microbes. Furthermore, N-9 causes damage to the vaginal epithelium, thus accelerating microbes to enter the women’s body. For this reason, antimicrobial peptides (AMPs), naturally secreted by all forms of life as part of innate immunity, deserve evaluation for their potential spermicidal effects. To date, twelve spermicidal AMPs have been described including LL-37, magainin 2 and nisin A. Human cathelicidin LL-37 is the most promising spermicidal AMP to be further developed for vaginal use for the following reasons. First, it is a human AMP naturally produced in the vagina after intercourse. Second, LL-37 exerts microbicidal effects to numerous microbes including those that cause STI. Third, its cytotoxicity is selective to sperm and not to the female reproductive tract. Furthermore, the spermicidal effects of LL-37 have been demonstrated in vivo in mice. Therefore, the availability of LL-37 as a vaginal spermicide/microbicide will empower women for self-protection against unwanted pregnancies and STI.

Objective To determine the minimum effective concentration (MEC) of an imbibing and soluble nonoxynol-9 (N-9) diaphragm (ISND) required for immobilisation of all spermatozoa in vitro and in vivo. The speed of semen absorbance, time of ISND to dissolution, and the antifertility effects were also investigated in rabbits. Methods In vitro spermicidal tests with ISND were conducted using fresh semen from humans and rabbits. Spermicidal and antifertility effects were observed in vivo after the ISND was placed directly into the vagina of rabbits. Results The MEC of N-9 required in the ISND to totally immobilise sperm within 20 seconds was 0.15 mg/ml for human sperm, and 0.5 mg/ml for rabbit sperm. The human semen was absorbed into the ISND in 45 minutes; the diaphragm dissolved in the vagina 3.5 hours later. In vivo, in rabbits, the MEC of N-9 required to immobilise sperm within five minutes of mating was 1 mg/kg in the ISND, and 10 mg/kg for the nonoxynol-9 film. The median effective dose of N-9 in the ISND was 1.07 mg/kg, whereas for the film it was 3.30 mg/kg. Conclusion The spermicidal and antifertility activities of a low dose N-9 in the ISND were high, with properties of imbibition and solubility confirmed. [ABSTRACT FROM AUTHOR]

Global statistics on unplanned pregnancies, abortions and STIs show that unprotected sex is still widely practised. More needs to be done to provide women and men with a wider choice of convenient protective options. To address this need, international efforts are focusing on developing multipurpose prevention technologies (MPTs) that address two or more indications simultaneously. These technologies would have significant advantages over single-indication products. They include inter alia novel barrier devices, drugs administered either as oral tablets or vaginal/rectal gels, drugs used in combination with medical devices, and genetically engineered organisms which secrete antimicrobial substances. As an example of progress in the MPT field, this paper describes an on-demand contraceptive/antimicrobial vaginal gel, Amphora (previously known as Acidform), now in an advanced stage of development. Clinical trials are currently being planned to find out whether this product's promising antimicrobial profile translates into protective and preventive choices. [ABSTRACT FROM AUTHOR]

Nonoxynol-9 (N-9), a microbicidal spermicide, has been in use as an over-the-counter contraceptive since the 1960s. A detailed account of its pharmacokinetic profile using highly sensitive detection method has not been reported yet. We developed and validated a rapid, selective and sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for N-9 detection in plasma and simulated vaginal fluid. The analytes were quantified using reverse phase Thermo Accucore C18 (150mm×4.6mm, 5µm) column with isocratic elution using acetonitrile: 0.1% formic acid in triple distilled water (90:10, v/v) as mobile phase. The ionization was optimized using ESI (+) and selectivity was achieved by tandem mass spectrometric analysis using MRM transition, m/z 617.4→133.2 for N-9 and m/z 180.1→138.1 for phenacetin. The method was linear over the range 0.195-100ng/mL. The method was accurate and precise with intra-batch and inter-batch accuracy (% bias) of less than ±15% and precision (% CV) of <15% for N-9. The mean peak plasma concentration (Cmax) 4.87±0.37ng/mL was achieved 1.0h after vaginal application with terminal half-life 1.45±0.07h in rabbits. The validated method was successfully applied for pharmacokinetic study of N-9 in rabbits after vaginal administration. [ABSTRACT FROM AUTHOR]

Abstract: Objective: ACIDFORM is a candidate microbicide with spermicidal properties. A large Phase 3 trial is underway, and it is anticipated that this product will be approved for contraceptive use and marketed soon in the United States. The goal of this article is to critically review the evidence supporting the properties, safety profile and different uses of ACIDFORM gel. Study design: We searched PubMed and Medline for any published literature on ACIDFORM. Results: ACIDFORM is an acidifying agent that works by lowering the vaginal pH to enhance the normal vaginal defenses. In addition to strong acid-buffering properties, ACIDFORM has high bioadhesive and viscosity-retaining properties. Several Phase 1 clinical trials have demonstrated the vaginal safety of ACIDFORM used alone or in combination with a diaphragm, although dose-dependent side effects appear to be present. Studies investigating the efficacy of ACIDFORM against sexually transmitted infections (STIs) are promising, but further trials are needed. Conclusions: The properties of ACIDFORM offer many advantages for use, either alone or in combination with another active ingredient, such as Tenofovir. Potential applications for ACIDFORM include use as a personal lubricant, a vaginal contraceptive (alone or with a barrier method) and a microbicidal product or as a formulation vehicle for an active ingredient. Implications: ACIDFORM is a candidate female-controlled vaginal preparation with microbicidal and spermicidal properties. A dual protection method could prevent unwanted pregnancies and reduce the risk of STI acquisition. [Copyright &y& Elsevier]

Rhynchosia volubilis Lour has been a major drug in a folk prescription for contraception in China, whereas its mechanism remains unknown. Its antifertility effects on male mice and antimicrobial activities on sexually transmitted infection (STI) pathogens were previously reported. This study was undertaken to develop the n-Butanol extract of Rhynchosia volubilis Lour (BERVL) as a spermicidal agent with STI prevention. The spermicidal activities of BERVL with different doses were assessed using selected high-motile sperms of normal human semen samples, and their inhibitory effects on Lactobacillus acidophilus were determined. The mechanism of the spermicidal activity was explored by aqueous Eosin Y and Hoechst 33342/PI staining. The results showed spermicidal activities and inhibitory effects of BERVL on Lactobacillus acidophilus were dose-dependent. Dose of 90 mg/mL BERVL terminated all progressive sperm motility within 2 min, and had slight inhibitory effect on Lactobacillus acidophilus, suggesting it was an effective and safe dose for contraception use. About 80% sperms exposed to BERVL displayed changes consistent with high permeability of head membrane. It is concluded that BERVL as spermicide has advantages over N-9 with strong ability to instantaneously kill human sperm and possesses light inhibitory effect on Lactobacillus acidophilus. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Curcumin, a component of the curry powder turmeric, has immense biological properties, including anticancer effects. The objective of this study was to determine if curcumin can provide a novel non-steroidal contraceptive having both spermicidal and microbicidal properties. Study design: The effect of curcumin, with and without photosensitization, was examined on human sperm forward motility and growth of several aerobic (n =8) and anaerobic bacteria (n =4) and yeast (n =7) strains implicated in vaginosis, vaginitis, and vaginal infections in women. The effect of various concentrations of curcumin on human sperm and microbes (aerobic and anaerobic bacteria and yeast) was tested. The effect on sperm was examined by counting the sperm forward motility, and on microbes by agar and broth dilutions and colony counting. Each experiment was repeated using different semen specimens, and bacteria and yeast stocks. Results: Curcumin caused a concentration-dependent inhibition of sperm forward motility with a total block at ≥250μM concentration. After photosensitization, the effective concentration to completely block sperm forward motility decreased 25-fold, now requiring only 10μM concentration for total inhibition. Curcumin concentrations between 100 and 500μM completely blocked the growth of all the bacteria and yeast strains tested. After photosensitization, the effective concentration to completely inhibit microbial growth decreased 10-fold for aerobic bacteria and yeast, and 5-fold for anaerobic bacteria. Conclusions: These findings suggest that curcumin can block sperm function and bacteria/yeast growth. It can potentially provide an ideal non-steroidal contraceptive having both spermicidal and microbicidal properties against vaginal infections. [Copyright &y& Elsevier]

Objectives: Little is known about the effects of commonly used lubricants on detection of biomarkers of semen exposure. We investigated the in vitro effect of Gynol®, K-Y Jelly®, Replens®, Astroglide®, Carbopol, and Silicorel on quantitative detection of prostate specific antigen (PSA). Study Design: A predetermined concentration of each of the gels was added to serially diluted semen samples. Additionally, serial dilutions of each of the gels were added to three different semen dilutions (high, medium, or low). The resulting samples were tested for PSA on the Abbott ARCHITECT System. Results: When using the Abbott ARCHITECT system, the only products that inhibited PSA detection were Gynol® and Replens®. The inhibition caused by Gynol® was dose-dependent, but that of Replens was dose-independent. K-Y Jelly®-spiked samples had higher PSA values than controls. Conclusions: Caution is warranted when using the Abbott quantitative assay for PSA detection as a biomarker of semen exposure in settings where Gynol®, Replens® or K-Y Jelly® might also have been used. Neither Astroglide® nor Silicorel inhibited PSA detection. Additional studies evaluating other vaginal products, including microbicides, and their effects on other assays, are needed. In vivo studies will be especially important to optimize PSA detection from clinical samples. Implications: Researchers should consider the potential for specific lubricants or any vaginal products to affect the particular assay used for semen biomarker detection. The Abbott ARCHITECT’s total PSA assay should not be used with the product Replens. Caution is warranted when using the assay in settings where Gynol or K-Y jelly may have been used. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can a specifically acting synthetic spermicide (DSE-37) be combined with a natural microbicide (saponins) for safe, prophylactic contraception? SUMMARY ANSWER A 1:1 (w/w) combination of DSE-37 and Sapindus saponins can target sperm and Trichomonas vaginalis precisely without any noticeable off-target effects on somatic cells at effective concentrations. WHAT IS KNOWN ALREADY Broad-spectrum vaginal agents like nonoxynol-9 (N-9) and cellulose sulfate have failed clinically as microbicides due to non-specific off-target effects, whereas agents that specifically target retroviruses have shown promise in clinical trials. DSE-37 and Sapindus saponins, respectively, specifically target human sperm and T. vaginalis in vitro. STUDY DESIGN, SIZE, DURATION A comprehensive study of efficacy and safety was undertaken using in vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37 and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal activities of the two components. N-9, the spermicide in clinical use, served as reference control. Free sperm thiols were fluorescently glinted to reveal differences in the targets of the test agents. PARTICIPANTS/MATERIALS, SETTING, METHODS On/off-target effects were evaluated in vitro against human sperm, T. vaginalis, HeLa, Vk2/E6E7, End1/E6E7 and Lactobacillus jensenii, using standard assays of drug susceptibility, cell viability, flow cytometric assessment of cell apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The spermicidal effect was also recorded live and free thiols on sperm were fluorescently visualized using a commercial kit. In vivo contraceptive efficacy (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune-labeling of inflammation markers VCAM-1, E-selectin and NFkB) were evaluated in rabbits. MAIN RESULTS AND THE ROLE OF CHANCE A 0.003% drug ‘combination’ containing 0.0015% each of DSE-37 and Sapindus saponins in physiological saline irreversibly immobilized 100% human sperm in ∼30 s and eliminated 100% T. vaginalis in 24 h, without causing any detectable toxicity to human cervical (HeLa) cells and Lactobacilli in 24–48 h, in vitro. N-9 at 0.003% exhibited lower microbicidal activity against Trichomonas but failed in spermicidal assays while causing severe toxicity to HeLa cells and Lactobacilli in 12–24 h. The ‘combination’ of DSE-37 and Sapindus saponins completely prevented pregnancy in rabbits at a vaginal dose of 20 mg (1% in K-Y Jelly), while application of 5% ‘combination’ in K-Y Jelly for 4 consecutive days caused negligible alterations in epithelial lining of rabbit vagina with only minor changes in levels of inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33% animals and a 4-day repeat application of 2% N-9 gel caused severe local toxicity to vaginal epithelium with molecular expression of acute inflammation markers. LIMITATIONS, REASONS FOR CAUTION The number of animals used for the in vivo efficacy study was limited by the approval of the animal ethics committee. WIDER IMPLICATIONS OF THE FINDINGS Anti-Trichomonal contraceptives with specifically acting synthetic component and clinically-proven safe natural component may define a new concept in empowering women to control their fertility and reproductive health. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by CSIR-Network Project ‘PROGRAM’ (BSC0101) and partly by the Ministry of Health and Family Welfare, Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s). [ABSTRACT FROM AUTHOR]

The relation between periconceptional vaginal permicide use and sex ratio at birth, birth weight, and the frequency of congenital anomalies was examined in a cohort of 2,712 New York City obstetric patients, 149 of whom (5.5 per cent) became pregnant while using spermicides or had used spermicides before and after conception. Periconceptional spermicide use was not associated with any important variation in the expected sex ratio at birth, nor with major or minor congenital anomalies. Exposure to spermicides in the periconceptional period defined dichotomously as present or absent, was not associated with decreased birth weight in male or female infants. There was a slight decrease in birth weight among female infants with increasing duration of postconceptional spermicide use an estimated 7.4 grams decrease with each day of use. The size of the effect and its selectivity by sex suggest a chance finding

Abstract: Background: Prostate-specific antigen (PSA) is a biomarker of recent semen exposure. There is currently only limited information on whether topical vaginal products affect PSA assays. We investigated this question using various dilutions of several vaginal products (lubricants and spermicides) and the Abacus ABAcard for PSA detection. Study Design: Pooled semen controls and various dilutions of nonoxynol-9 (N9), carboxymethyl cellulose (CMC), Replens, Gynol 2, K-Y jelly, Astroglide, Surgilube, combined with pooled semen dilutions, were tested for PSA using the Abacus ABAcard. Results: N9 (2% with saline) and CMC did not appear to affect the results of testing with the ABAcard, but not all semen dilutions were tested. The other products (including Replens and Gynol, which is 2% N9 with propylene glycol, K-Y, Astroglide and Surgilube) at some of the dilutions tested either affected or gave invalid results with PSA testing using the ABAcard. Both Gynol 2 and K-Y at 1:10 dilution gave false-positive results. Conclusions: Some vaginal products affect PSA results obtained by using the semiquantitative ABAcard. In vivo confirmation is necessary to further optimize PSA detection when topical vaginal products are present. [Copyright &y& Elsevier]

Background and objectives Sexually transmitted infections (STIs) and unplanned pregnancies have serious effects on the reproductive health of women. The present study was undertaken with a view to develop an effective means of prevention. The microbicidal and contraceptive potential of cationic peptides from frog's skin, namely, dermaseptin S4 and its derivatives were investigated in vitro. Study design Different bacterial and fungal strains were resorted to for determining the antimicrobial activity of the new compounds. The spermicidal activities of the latter were assessed using normal human semen samples, and their toxic effects were identified in a HeLa culture. Results All S4 derivatives elicited concentration-dependent spermicidal and antimicrobial activities at microgram concentrations. The highest levels recorded for both types of activity were displayed by K4K20S4, and the lowest levels were exhibited by D4D20S4 and S4(5-28). Cytotoxicity assays revealed that some of these compounds were significantly safer than nonoxynol-9 (N-9). Conclusions The ability of these peptides to instantaneously kill human sperm and STI pathogens at low concentrations indicates that their application as active ingredients in vaginal contraceptive preparations could induce considerably better effects than N-9. [ABSTRACT FROM AUTHOR]

Objective: To focus on the possible mechanism about the spermicidal effect of methanolic extract of leaves of Cestrum parqui (Solanacea) on human spermatozoa. Methods: Sperm motility and viability were noted according to the guideline of WHO. The morphological changes in chromatin materials and in plasma membrane at the head part of the spermatozoa were assessed under transmission electron microscopy (TEM). DNA fragmentation index (DFI) of spermatozoa in percentage was assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) using kits. For confirmation of DNA breakage, gel electrophoresis of DNA was conducted using 1.2 % agarose gel. Results: Sperm viability and motility were both decreased in dose-dependent manner from 50 to 300 μg/ml of methanolic extract in respect to the control. Loss of viability and motility both were noted 100% at the dose of 300 μg/ml within 5 min. From the microphotography it has been revealed that chromatin condensation at the dose of 200 μg/ml is more than the control without any noticeable alteration in plasma membrane. In contrast, chromatin decondensation has been noticed at the dose of 300 μg/ml along with a remarkable disruption in plasma membrane. Analysis of DNA damage by TUNEL revealed a significant elevation (P<0.01) in the level of % DFI at the dose of 200 μg/ml (moderate dose) after 17 h in respect to the control. But at the dose of 300 μg/ml, no significant variation was observed in this parameter upto 24 h of exposure though a significant variation (P<0.01) was noted after 48 h of exposure compared with the control. Gel electrophoresis of DNA also followed the same type of results i.e. 200 μg/ml affected DNA integrity but other doses were ineffective in this concern. Conclusion: The extract of Cestrum parqui at moderate dose exhibited spermicidal activity by inducing apoptotic pathway but at the high dose it caused necrosis. [Copyright &y& Elsevier]

Objective: To evaluate male antifertility activity of hydroalcoholic extract of Ficus racemosa bark. Methods: Swiss male mice were orally administered hydroalcoholic extract of Ficus racemosa bark (50 mg/kg for 30 d and 100 mg/kg body weight for next 30 d), and the effect of the treatment on body weight, reproductive organs weight, sperm, biochemical profile (sialic acid in epididymis and fructose in seminal vesicle), fertility and vaginal contraceptive efficacy was investigated. Recovery studies were also performed. Results: Extract reduced fertility to 70% within 60 d. Suppression of cauda epididymis sperm count, motility, viability and abnormal morphology was observed. Marked reduction was noted in the weight of reproductive organs and the level of sialic acid in epididymis and fructose in seminal vesicle. Vaginal application of bark extract exhibited 80% vaginal contraceptive efficacy. After cessation of plant extract treatment, the altered parameters recovered after 60 d. Conclusion: Clinical assessment of male antifertility agents should include acceptability, safety and efficacy during and after the treatment. The above results revealed the potential, reversible male antifertility effect of hydroalcoholic extract F. racemosa bark. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the spermicidal activity of Passiflora edulis extract on human spermatozoa. Methods: Human spermatozoa were incubated with P. edulis extracts and their motility and viability were evaluated; additionally, the cytotoxic effect of the extracts was evaluated by the tetrazolium bromide (MTT) reduction assay. Results: The motility and viability were decreased immediately after treatment with a 21% dilution of the supernatant of the extract of P. edulis (P<0.001). No cytotoxic effect of the extracts studied was found on proliferation of MDBK and VERO cells. Conclusion: These results may open the way for the use of P. edulis as a spermicidal product with less adverse effects. [Copyright &y& Elsevier]

The seed extracts of Madhuca latifolia were reported to have spermicidal activity. The current investigation identified the spermicidal component of the extracts and evaluated its spermicidal potential in vitro. As characterized by infrared, mass, and nuclear magnetic resonance (NMR) spectral analyses, Mi-saponin A (MSA) was found to be the most potent component among a mixture of saponins. The mean effective concentrations of MSA that induced irreversible immobilization were 320 µg/mL for rat and 500 µg/mL for human sperm, as against the respective concentrations of 350 and 550 µg/mL of nonoxynol 9 (N-9). The mode of spermicidal action was evaluated by a battery of tests including (a) double fluoroprobe staining for spermviability, (b) hypoosmotic swelling test and, assays for 5′ nucleotidase and acrosin for physiological integrity of sperm plasma membrane, (c) scanning and transmission electron microscopy for sperm membrane ultrastructure, and (d) plasma membrane lipid peroxidation (LPO). The observations, taken together,were interpreted to mean that the spermicidal effect of MSA involved increased membrane LPO leading to structural and functional disintegration of sperm plasma membrane and acrosomal vesicle. A comparative in vitro cytotoxicity study in human vaginal keratocyte (Vk2/E6E7) and endocervical (End/E6E7) cell lines demonstrated that the 50% cell cytotoxicity (CC50) values, and consequently the safety indices, for MSA were ≥ 8-fold higher as compared to those of N-9. In conclusion, MSA is a potent spermicidal molecule that may be explored further for its suitability as an effective component of vaginal contraceptive. [ABSTRACT FROM AUTHOR]

Of the variety of contraceptive options available for women, very few provide dual protection against sexually transmitted diseases. Due to increased incidence of human immunodeficiency virus type 1 (HIV-1), genital herpes, hepatitis B and human papilloma virus, development of novel contraceptive strategies that incorporate antiviral activity has become the top priority in contraceptive research. Topical microbicides are now considered to be the last ray of hope, as they would ideally provide protection against unwanted pregnancy, proper lubrication during sexual activity, and preclude the vaginal/rectal transmission of sexually transmitted diseases. A large number of vaginal microbicides are in the preclinical or clinical stages of evaluation for their safety, efficacy and acceptability. However, a major bottleneck in the development of novel mechanism-based dual microbicides has been their detergent-like effects, along with debilitating action on the vaginal microflora. Hence the search is still on for the ideal dual microbicide/s that may obliterate these disadvantages and provide an invincible shield to women in their crusade against unintended pregnancy as well as sexually transmitted diseases. The present review highlights the current scenario towards the development of novel contraceptive strategies to counteract the rampant spread of sexually transmitted diseases, with special reference to HIV/AIDS. [ABSTRACT FROM AUTHOR]

Objective: To determine the spermicidal activity of antisemen antibodies in the hamster model.Design: Prospective, controlled study.Setting: Advanced preclinical sciences center.Animal(s): Subgroups of 10 and 14 golden hamsters.Intervention(s): Ex vitro and in vivo treatment of sperm with antisemen antibodies or normal rabbit serum.Main Outcome Measure(s): The EC(50) value of antisemen antibodies, the time required for 50% motility loss of progressively motile spermatozoa exposed to antisemen antibodies, the average sperm mitochondrion fluorescence intensity, the rate of fertilization, and the scoring of histologic changes in the hamster vaginal tissue.Result(s): The EC(50) value of antisemen antibodies was found 70 microg/mL, and the time required for 50% motility loss of progressively motile spermatozoa exposed to antisemen antibodies (at 70 microg/mL) was 5 minutes; for the experimental and control groups, the average fluorescence intensities of sperm mitochondria were respectively 180.28 +/- 82.24 and 309.74 +/- 148.37, the fertilization rates in vitro were 0.09% and 45%, the rates of fertilization with intrauterine sperm injection were 0 and 15.0%. There was a significant difference between two groups. None of the four hamsters that received antisemen antibodies in gel-polyoxyl-40-stearate had epithelial disruption characteristic of inflammation.Conclusion(s): Antisemen antibodies possess appreciable spermicidal potential, which may be explored as an effective constituent of spermicide. [ABSTRACT FROM AUTHOR]