Biodegradable implants based on photo-cross-linked aliphatic polycarbonates for long-acting contraception

In this study,a new class of biodegradable contraceptive implants was prepared via the UV irradiation molding method,among which,progestin levonorgestrel(LNG)was used as a model drug.Photo-cross-linked aliphatic polycarbonates(APCs),namely,poly(trimethylene carbonate-co-2,2′-dimethyltrimethylene carbonate)[P(TMC-co-DTC)]elastomers,were used as the drug delivery matrix.The results obtained from the degradation experiments carried out in Sprague-Dawley(SD)rats showed that the cross-linked elastomer had the degradation characteristics of the surface erosion degradation mechanism,with no generation of acid degradation products,and excellent form-stability,which met the performance requirements of the matrix for a long-acting sustained-release delivery system.The in vitro cytotoxicity tests and histological and immunohistochemical evaluations showed good biocompatibility and biosafety of the elastomer matrix material and contraceptive implants.Subsequently,the implant formulations were screened by in vitro release experiments,and their release kinetics were explored.Finally,in the evaluation study of the in vivo anti-fertility effect,the implants exhibited excellent dimensional stability and were degraded by a surface erosion mechanism.LNG achieved a stable and sustained release in female SD rats,maintaining a long-acting contraceptive duration of up to 4 months.The contraceptive implants obtained in this study could be used to address the limitations of currently available formulations,which required secondary surgical removal and a single means of regulating drug release kinetics.Therefore,these implants could provide a new option for birth control needs and may be of significance in reducing the incidence of induced abortion and protecting female fertility.

Measuring Cognitive and Psychosocial Accessibility to Modern Contraception: A Comprehensive Framework

Nowadays, more than ever, the improvement of access to family planning (FP) has become an international goal. What constitutes access to FP? Current human rights-based contraceptive guidelines indicate that access begins as soon as women or couples express a desire to avoid pregnancy and their risk of unintended pregnancy is established. However, few studies have sought to define and measure cognitive and psychosocial access to contraception. To propose a comprehensive framework for the cognitive and psychosocial accessibility of contraception, we critically analyzed the literature on attitudes toward FP. The main dimensions that emerged were knowledge about FP, fear of side effects, approval of contraception, and contraceptive agency. We then identified and adjusted some questions that can capture these dimensions more comprehensively. As a result, we developed a questionnaire module comprising 15 questions, which was integrated into the 6th round of the PMA2020 survey in Burkina Faso in 2019. This research highlighted that previous studies have collected separate dimensions of contraceptive access, and the psychosocial dimension tended to be neglected. Our results demonstrate that it is possible to collect comprehensive data on cognitive and psychosocial dimensions of access to family planning.

Female Contraception: Comparative Study of Biometrics and Vascularization of the Uterus at Sylvanus Olympio University Hospital (Togo)

Female contraception uses both hormonal and non-hormonal methods. The aim of the study is to determine the impact of female contraception on uterine vascularisation and the endometrium. Method: It was a descriptive comparative study with an analytical aim. It took place at the University Clinic of Obstetrics Gynaecology and the Radiology and Medical imaging Department of Sylvanus Olympio University Hospital in Lomé over a two-month period from May 15, 2023 to July 15, 2023. Group 1 included women using a modern contraceptive method and group 2 women not using a modern contraceptive method. Epidata 3.1 and R 4.0.4 software were used to process the data. Results: Each group included 50 women. There were no significant differences in uterine and endometrial biometrics. All women on contraception had their zone 1 vascularized, without vascularisation of zone 2, without significant difference with women without contraception The pulsatility index was greater than 3 in 51% (n = 51) of women, including 62.7% (n = 32) of women without contraception and 37.3% (n = 19) of women on contraception, with a statistically significant difference (p = 0.009). Conclusion: Contraceptive methods do not influence the biometry of the uterus. However, uterine artery Doppler indices can predict abnormal uterine bleeding.

Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

The Use of Modern Contraception after Childbirth in an Urban Health Center in Bangui, CAR

Introduction: The use of modern postpartum contraception not only reduces unplanned pregnancies but also improves the well-being of mother and child. The present study aims to identify the determinants of postpartum contraceptive use in a first level health facility. Methodology: This was a 6-month cross-sectional study conducted at the Urban Health Center of Castors. Postpartum women who presented within 42 days of delivery and who had a live child were included after informed consent. Results: Of 318 women enrolled during the study period, 106 were currently using a modern contraceptive method, for a prevalence of 33.3%. The mean age of the women was 25.3 years (±3.6), with extremes of 14 and 49 years. The age group [20 to 29] was the most represented with 52.8%. More than half of the women were in couples (54.7%) and had completed secondary education (53.8%). These women were mostly students (42.5%) and primiparous or pauciparous (70.7%). The most used contraceptive method was injectables (depot medroxyprogesterone acetate) (43.4%), followed by male condoms (23.6%) and oral contraceptives (17.9%). The unmet need for contraception was 40.6%. The main reasons for non-use were the desire to have more children (41.5%), fear of side effects (34.9%) and spousal opposition (12.3%). Factors associated with contraceptive non-use were educational level, occupation and parity. Conclusions: The rate of modern contraceptive use in the postpartum period is low in the study population. Interventions to increase the use of effective contraceptive methods are needed, especially among young women.

Factors Influencing the Choice between IUD and Implant among Long-Acting Reversible Contraceptive (LARCs) Users in Burkina Faso

Background: Long-acting and reversible contraceptive methods hold great potential as solutions to address the unmet need for contraception and the significant discontinuation rates, especially in sub-Saharan Africa. Among these methods, the Implant has gained popularity in sub-Saharan Africa, whereas the utilization of Intrauterine Devices (IUDs) has remained comparatively low, particularly in Burkina Faso. This study aims to evaluate the shifts in IUD and Implant usage from 2010 to 2020 and to pinpoint the factors influencing the choice of IUDs among LARCs users in Burkina Faso. Data and Methods: We conducted an analysis using data from Burkina Faso, drawn from the 2010 Demographic and Health Survey (DHS) and the 2020 PMA Phase 1 data. The 2010 DHS garnered responses from 17,087 women aged 15 - 49, achieving a response rate of 98.4%. The 2020 PMA data collected responses from 6590 women aged 15 - 49, with a response rate of 95.8%. The final sample of Long-Acting Reversible Contraceptives (LARCs) users consisted of 1502 women, including 576 women from the 2010 survey and 926 women from the 2020 survey. Results: The study demonstrates an expansion of IUD usage to include socioeconomically disadvantaged segments among LARC users. However, higher levels of education, older age, and decisions influenced by healthcare providers are correlated with the preference for IUDs over Implants. The choice of IUDs is also connected to a comprehensive understanding of contraceptive methods, suggesting potential biases in the counseling process. Conclusion: Facilitating the broader adoption of IUDs among disadvantaged groups could be achieved by improving the accessibility of IUD products and services in rural areas. Nevertheless, there should be focused initiatives to enhance access to removal services, as this factor could dissuade specific users. Further efforts are required to train healthcare providers, aiming to mitigate biases in delivering Long-Acting Reversible Contraceptives (LARCs). Providers should provide impartial counseling, irrespective of the selected type of LARC.

Low dose gossypol for male contraception

Aim: To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose re-duction. Methods: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10 mg gossypol(29 cases) and 12.5 mg (26 cases). Serum levels of testosterone, FSH and LH were measured by RIA and potassiumby flame photometry. Spema counts and motility were examined before and regularly after treatment for the evaluationof contraceptive efficacy. Results: The average sperm density and motility started to decrease significantly by theend of month 2 of medication and gradually reached the infertility levels ( < 4 million /mL) in both treated groups. Af-ter that the 10 mg group was asked to take the same dose every other day for up to a total observation period of 16-18months for the maintenance of infertility. Subjects in the 12.5 mg group did not take gossypol any more so as to ob-serve the length of the loading dose required, but in a few, a maintenance dose of 12.5 mg every other day was insti-tuted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose pe-riod. Serum levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteercomplained of myoasthenia. After cessation of drug administratioin, the semen data returned to pretreatment levels.Conclusion: A regimen with 10 or 12.5 mg of gossypol as the daily loading dose and 35 or 43.75 mg as the week-ly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.(Asian J Androl 2000 Dec; 2: 283-287)

Vas deferens, a site of male contraception: an overview

The vas deferens is a site which can be exploited for male contraception without undue side effects. The only ef-fective technique available for male contraception is vasectomy, being practiced world wide, despite that it is a perma-nent surgical procedure and its successful reversal is not assured. Although no-scalpel vasectomy minimizes surgicalprocedures, the fate of its reversal is akin to that of vasectomy. Several occlusive and non-occlusive vasal procedureswhich claim to be reversible without surgical intervention, possess more disadvantages than advantages. Vas occlusionwith plug, ' Shug' or medical grade silicone rubber, although claimed to produce reversible azoospermia without affect-ing spermatogenesis, requires skilled microsurgery for their implantation and later removal. RISUG^R, a non-scleroticpolymer styrene maleic anhydride (SMA), could be more advantageous than vasectomy and other vas occlusive proce-dures in that it could be a totally non-invasive procedure by 'no-scalpel injection' and 'non-invasive reversal'. It isclaimed to offer long-term contraception without adverse side effects and also to be possible as a male spacing methodby repeated vas occlusion and non-invasive reversal. The drug is currently under multicentre Phase Ⅲ clinical trial.

Approaches to post-testicular contraception

The induction of infertility in males of several species through epididymal interference is more difficult to achieveby reduction of the mounts of epididymal secretions (eg α-glucosidase, L-carnitine) or immunological interferencewith secreted proteins ( eg D/E, P34H, P26h) than by direct actions of drugs on sperm function (eg inhibition ofglyceraldehyde 3-phosphate dehydrogenase by chloro-compounds). The latter approach holds promise for mankind ashuman sperm are susceptible to glycolytic inhibition. Future contraceptive developments may arise from production oftargeted inhibitors, research on the displacement of sperm proteins in the epididymis and interference with sperm plasmamembrane ion channels.

Development of methods of male contraception: impact of the World Health Organization Task Force

Objective: To give an historical record of the research of the World Health Organization (WHO) Task Force to develop methods of male contraception; to examine the social, political, medical, pharmaceutical, funding, and other factors that influenced progress; and to suggest reasons why such methods are only now becoming available. Design: Review of basic and clinical research over 30 years. Setting: Task force of a multinational agency and collaborating agencies. Conclusion(s): Through the involvement of many international scientists, the WHO Task Force has uniquely contributed to the exploratory phases of the research in male contraception and by its multicenter contraceptive efficacy studies has accelerated progress towards the ideal hormonal method. Despite an adverse climate involving social and political attitudes, funding constraints, and pharmaceutical industry hesitations, WHO formed coalitions with governments and international agencies to sustain research with results that apply to men in culturally diverse populations and thereby to influence activities across the whole range of global reproductive health and family planning.

Hormonal contraception in Chinese men: variations insuppression of spermatogenesis with injectable testosteroneundecanoate and levonorgestrel implants

Aim: To explore the causes of the difference in spermatogenic suppression between responders and non-responders in Chinese men treated with levonorgestrel (LNG) implants plus testosterone undecanoate (TU) injectable. Methods: The 16 Chinese volunteers treated were divided into two groups in regard to the sperm count during the treatment period, 7 men in the responder group (Group R), including 6 azoospermia and one severe oligozoospermia, and the remaining 9 in the non-responder group (Group N), including 4 oligozoospermia and 5 with sperm counts greater than 20×106/mL. The differences in serum profiles of FSH, LH, T, LNG and T/LH ratio were compared between the two groups and the correlation between the seminal fluid parameters and serum reproductive hormones was analyzed. Results: The serum FSH level was lower in Group R than that in Group N (P<0.05), while the serum LH and LNG levels were higher in Group R than those in Group N (P<0.05). The sperm density (P<0.01, r=0.235), motility (P<0.01, r=0.326) and vitality (P<0.01, r=0.219) showed significantly positive correlation with the serum FSH level. Conclusion: The blood LNG and T levels, the degree of FSH inhibition and/or the sensitivity of the pituitary-testis axis to exogenous steroids, as well as the individual spermatogenetic potential and the functional status of the Leydig cells may be factors bringing about individual differences in spermatogenic suppression in Chinese men treated with LNG and TU.

Three new methods for male contraception

The methods devised for male contraception are meagre. In the crrrent communication, we review 3 recently de-veloped methods applied for male contraception: testicular suspension, polyester-induced azoospermia and prolactin in-jection. The testicle was suspended in the superficial inguinal pouch close to the scrotal neck using 2 methods: stitchand ball. The azoospermic effect of the polyester sling seems to be due to 1) creation of electrostatic field across theintrascrotal structures, and 2) disordered thermoregulation. Prolactin administration, as a contraceptive method is effi-cient and safe and has the potential to be developed as a male contraceptive. The effect of the above mentioned 3methods is reversible. These methods, especially testicular suspension and polyester suspensors, are simple and easilyapplicable and were well acceptable by the subjects. (Asian J Androl 1999 Dec; 1: 161 - 167)

More than eight years＇ hands-on experience with the novel long-acting parenteral testosterone undecanoate

Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.

Hormonal contraception for human males:prospects

Development of an ideal hormonal contraceptive for man has been the goal of several research workers during thepast few decades. Suppression of pituitary gonadotropic hormones, which in turn would inhibit spermatogenesis whilemaintaining normal libido and potentia has been the approach for a contraceptive agent. Intramuscularly administeredand orally active testosterone or testosterone in combination with progesterone have been shown to cause inhibition ofspermatogenesis resulting in azoospermia in normal men. Similarly testosterone has been used in combination with go-nadotropin releasing hormone antagonists and agonists to inhibit pituitary gonadotropic hormone release. Immunologicalapproach to neutralize the circulating levels of follicle stimulating hormone has also been shown to cause inhibition ofspermatogenesis. The available literature shows that testosterone causes reversible azoospermia without any significantside effects in Asian population effectively and appears to be a promising chemical for control of fertility in man.

Interference with the formation of the epididymal microenvironment——a new strategy for male contraception?

The cystic fibrosis transmembrane conductance regulator (CFIR) or the small conductance cAMP-activated chlo-ride channel encoded by the CFTR gene has been shown to play an important role in the formation of the epididymalfluid microenvironment. Recent work in our laboratory has shown that this protein is also expressed by developing germcells indicating a role of this protein in spermatogenesis. In view of the fact that the CFTR gene has a far reaching andwidespread effect on human reproduction, understanding the role of CFTR in the male reproductive tissues and its inter-vention by pharmacological agents can open a new avenue of research into the development of novel male contracep-tives. (Asian J Androl 2000; 2: 39 - 45 )

Predictors for partial suppression of spermatogenesis of hormonal male contraception

Aim： To analyze factors influencing the efficacy of hormonal suppression of spermatogenesis for male contraception. Methods： A nested case-control study was conducted, involving 43 subjects, who did not achieve azoospermia or severe oligozoospermia when given monthly injections of 500 mg testosterone undecanoate （TU）, defined as partial suppressors compared with 855 subjects who had suppressed spermatogenesis （complete suppressors）. Sperm density, serum testosterone, luteinizing hormone （LH） and follicle stimulating hormone （FSH） concentrations at the baseline and the suppression phase were compared between partial and complete suppressors. Polymorphisms of androgen receptor （AR） and three single nucleotide variants and their haplotypes of FSH receptor （FSHR） genes determined by polymerase chain reaction （PCR） and DNA sequencing technique were compared between 29 partial and 34 complete suppressors. Results： Baseline serum LH level was higher and serum LH as well as FSH level during the suppression phase was less suppressed in partial suppressors. Additionally, in a logistic regression analysis larger testis volume, higher serum FSH concentrations alone, or interaction of serum LH, FSH, testosterone and sperm concentrations were associated with degree of suppression. The distribution of polymorphisms of AR or FSH receptor genes did not differ between partial and complete suppressors. In cases with incomplete FSH suppression （FSH 〉 0.2 IU/L）, the chances of reaching azoospermia were 1.5 times higher in the subjects with more than 22 CAG triplet repeats. Conclusion： Partial suppression of spermatogenesis induced by 500 mg TU monthly injections is weakly influenced by hormonal and clinical features but not polymorphism in AR and FSHR genes.

Intra-Articular injection of acid-sensitive stearoxyl-ketal-dexamethasone microcrystals for long-acting arthritis therapy

Despite advances in treatment of chronic arthritis,there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues.In this work,we fabricated microcrystals of an acid-sensitive stearoxyl-ketal-dexamethasone prodrug for treatment of arthritis.Microcrystals of the prodrug with two sizes were successfully engineered and showed pH-dependent hydrolysis kinetics in vitro.In a collagen-induced arthritis rat model,we evaluated the influence of particle size and injection dose on anti-inflammatory effect after intra-articular injection.Such prodrug demonstrated long-acting anti-arthritis effects with good safety.Our results indicate ketal-based prodrugs are promising for the development of long-acting injectables and may stimulate the development of new treatments for chronic diseases.

Assessment of level of knowledge and utilization of emergency contraception among female students of Hawassa University, south Ethiopia

Introduction: Emergency contraception is used as an emergency procedure to prevent unintended pregnancy secondary to an unprotected se xual intercourse and method failure. Hence, this study assessed the level of knowledge and utilization of emergency contraception among undergraduate regular female students of Hawassa University, south Ethiopia. Methods: An institution-based cross-sectional survey was conducted among female students of Hawassa University in December 2012. Seven hundred seventy six of the students were sampled by using multistage sampling technique. Pretested structured questionnaire was used to collect the data. Results: The majority 719 (92.7%) of female university students ever had sexual intercourse and 17 (2.2%) experienced forced sex. Eight (47%) of these 17 students experienced unintended pregnancy all of which resulted in an induced abortion. Three hundred seventy nine (72.2%) of the respondents had knowledge about emergency contraceptives and only 41 (10.8%) of them had ever used emergency contraceptives;oral contraceptive pills were the most widely used form of all emergency contraceptives 41 (10.8%). Age, marital status and age at menarche were associated with knowledge of emergency contraception;moreover, residence, year of study and experience of forced sex were found to be predictors of emergency contraception utilization. Conclusion: Female university students had been experiencing high rate of unintended sexual practice and pregnancy, low knowledge level and utilization of emergency contraceptives;moreover, they had no youth-friendly access to the services. Therefore, there is a need for collaborated effort to improve service access and scale up their utilization level to prevent unwanted pregnancy.

Thermal stability and long-acting antibacterial activity of phosphonium montmorillonites

Na-montruorillonite （Na-MMT） was exchanged with three quaternary atkylphosphonium salts： decyl tributylphosphonium bromide （DTBPBr）, dodecyl tributylphosphonium bromide （DDTBPBr） and hexadecyl tributylphosphonium bromide （HDTBPBr）, to investigate the effects of phosphonium salts species and relative molecular mass on the characteristics, morphology, thermal stability and long-acting antibacterial property of phosphonium montmorillonites. The resulting modified montmorillonites were characterized by the FTIR, XRD, TEM, and TG/DTG techniques. And minimum inhibitory concentration （MIC） was used to investigate antibacterial activity. The results show that the phosphonium salts are intercalated into Na-MMT, and the basal spacing of P-MMTs is enlarged with the increase of phosphonium salt content or the growth of alkyl chain length. DDTBP-MMT-3 with 19.83% （mass fraction of dodecyl tributylphosphonium salts, displays excellent thermal stability and long-acting antibacterial activity.

Evaluation of intratesticular chlorhexidine gluconate for chemical contraception in dogs

Objective:To investigate the contraceptive effect of intratesticular injection of chlorhexidine gluconate in dogs and compare it with that of zinc gluconate neutralized with arginine.Methods:Twenty-four sexually mature male mongrel dogs were randomly divided by replicate into four groups(n=6 per group).GroupⅡreceived intra-testicular injection of 2 mL zinc gluconate(10 mg/mL)neutralized with arginine.GroupⅡreceived intratesticular injection of 2 mL chlorhexidine gluconate(5%w/v).GroupⅢreceived intratesticular injection of 2 mL chlorhexidine gluconate(4%w/v).GroupⅣdid not receive any treatment and served as the control group.Testicular morphometry was conducted on day 0,7,15 and 30 after treatment.Semen was collected and evaluated on day 0 and 30.Data were analyzed using repeated measures analysis of variance.Results:There was no difference in the mean values of various parameters between dogs treated with zinc gluconate and those treated with chlorhexidine gluconate at any of the time points.In dogs treated with zinc gluconate or chlorhexidine gluconate,there was a significant increase in the testicular morphometric parameters on day 7 followed by a significant reduction thereafter(day 15 and 30).In contrast,there was no change in any of the parameters in the control untreated dogs during the course of the study.Compared to the pre-treatment values,the mean scrotal circumference and the mean paired testicular volume and testicular weight on day 30 were significantly lower in the treated dogs.Semen samples collected on day 30 from treated dogs were found to be azoospermic,whereas no change in semen quality was observed in the control untreated dogs.Conclusions:Intratesticular injection of chlorhexidine gluconate(5%w/v and 4%w/v)is equally as effective as zinc gluconate neutralized with arginine for chemical contraception in dogs.