scholarly journals Engineering highly multivalent sperm-binding IgG antibodies for potent non-hormonal female contraception

2020 ◽  
Author(s):  
Bhawana Shrestha ◽  
Alison Schaefer ◽  
Jamal Saada ◽  
Zhu Yong ◽  
Timothy M. Jacobs ◽  
...  
Keyword(s):  
Hormonal Contraception ◽  
Human Sperm ◽  
Hormonal Contraceptive ◽  
Medical Applications ◽  
Motile Sperm ◽  
Igg Antibodies ◽  
Contraceptive Methods ◽  
Sperm Binding ◽  
Polymeric Immunoglobulins ◽  
Unique Surface

AbstractMany women risk unintended pregnancy due to dissatisfaction with available hormonal contraceptive methods. This led us to pursue topical sperm-binding monoclonal antibodies as a strategy for safe, non-hormonal contraception. Motivated by the greater agglutination potencies of polymeric immunoglobulins such as IgM and the exceptional bioprocessing ease in manufacturing IgG, we engineered IgGs possessing 6-10 Fabs against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) are at least 10- to 16-fold more potent and faster than the parent IgG at agglutinating sperm, while preserving Fc-mediated trapping of individual spermatozoa in mucus. The increased potencies translate to effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using 33 micrograms of the 10 Fab HM-IgG. HM-IgGs produce at comparable yields and possess identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for non-hormonal contraception but also a promising platform for generating potent agglutinating mAb for diverse medical applications.

Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception

2021 ◽  
Vol 13 (606) ◽  
pp. eabd5219
Author(s):  
Bhawana Shrestha ◽  
Alison Schaefer ◽  
Yong Zhu ◽  
Jamal Saada ◽  
Timothy M. Jacobs ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Reproductive Tract ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Infertile Woman ◽  
Igg Antibodies ◽  
Contraceptive Methods ◽  
Sperm Binding ◽  
Polyvalent Immunoglobulins ◽  
Unique Surface

Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.

scholarly journals Férfi hormonális fogamzásgátlás: múlt, jelen, jövő

2017 ◽  
Vol 158 (46) ◽  
pp. 1819-1830 ◽  
Author(s):  
Norbert Pásztor ◽  
Borbála Eszter Hegyi ◽  
Attila Badó ◽  
Gábor Németh
Keyword(s):  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Hormonal Contraception ◽  
Hormonal Contraceptive ◽  
Contraceptive Methods ◽  
Luteinizing Hormone Secretion ◽  
The World ◽  
Effective Contraception ◽  
In The Beginning ◽  
Contraceptive Agent

Abstract: In certain regions of the world the enormous rate of population growth raises economic and public health concerns and widely accessible contraceptive methods would be desired. In contrast, in other countries the use of effective contraception is a question of individual preferences. Today, most of the reliable contraceptive methods are applied by women, while the options for male methods are quite limited. It is well known that significant portion of pregnancies are still unplanned and several data revealed men’s willingness to take part in family planning. Based on these needs, remarkable efforts have been made to develop a suitable hormonal contraceptive agent for men. With the exogenous suppression of follicle stimulating hormone and luteinizing hormone secretion, the inhibition of the testicular testosterone production and the spermatogenesis can be achieved. In the beginning, testosterone-derivatives, or testosterone-progestin combinations were administered, later synthetic androgen agents were developed. Despite of these efforts, unfortunately, there is no safe, widely feasible male hormonal contraception to date, but in the future this goal can be achieved by solving the key hurdles. Orv Hetil. 2017; 158(46): 1819–1830.

scholarly journals Hexavalent Sperm-Binding IgG Antibody Released from Self-Dissolving Vaginal Film Enables Potent, On-Demand Non-Hormonal Female Contraception

2021 ◽  
Author(s):  
Bhawana Shrestha ◽  
Kathleen Vincent ◽  
Alison Schaefer ◽  
Yong Zhu ◽  
Gracie Vargas ◽  
...  
Keyword(s):  
Molecular Orientation ◽  
Expression System ◽  
Hormonal Contraception ◽  
Water Soluble ◽  
Motile Sperm ◽  
Igg Antibody ◽  
On Demand ◽  
Sperm Binding ◽  
Vaginal Film ◽  
Work Supports

Non-hormonal products for on-demand contraception are a global health technology gap, motivating us to pursue the use of sperm-binding monoclonal antibodies as a strategy to enable safe, effective, desirable, on-demand contraception. Here, using cGMP-compliant Nicotiana-expression system, we produce an ultra-potent sperm-binding IgG antibody possessing 6 Fab arms per molecule that bind a well-established contraceptive antigen target, CD52g. We term this hexavalent antibody Fab-IgG-Fab (FIF) to reflect its molecular orientation. The Nicotiana-produced FIF exhibits at least 10-fold greater sperm agglutination potency and kinetics than the parent IgG, while preserving Fc-mediated trapping of individual spermatozoa in mucus. We formulate the Nicotiana-produced FIF into a polyvinyl alcohol-based water-soluble contraceptive film, and evaluate its potency in reducing progressively motile sperm in the sheep vagina. Two minutes after vaginal instillation of human semen, no progressively motile sperm are recovered from the vaginas of sheep receiving FIF-Film. In contrast, high numbers of progressively motile sperm are recovered from sheep receiving a placebo film control. Our work supports the potential of highly multivalent contraceptive antibodies to provide safe, effective, on-demand non-hormonal contraception.

scholarly journals Hormonal Contraception and Diabetes

2012 ◽  
Vol 5 ◽  
pp. CMWH.S9934
Author(s):  
L.F. Pallardo ◽  
A Cano ◽  
I Cristobal ◽  
M.A. Blanco ◽  
M Lozano ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Preconception Care ◽  
Microvascular Complications ◽  
Hormonal Contraception ◽  
Hormonal Contraceptive ◽  
Contraceptive Methods ◽  
Type 2 Dm ◽  
Increased Risk

Women with gestational diabetes mellitus are at increased risk for developing diabetes mellitus (DM), mainly type 2 DM, as well as metabolic syndrome. The presence of subsequent pregnancies increases the risk. In addition, pregnancy in patients with type 1 and type 2 DM also elevates the risk of morbidity and mortality for both mothers and offspring. Thus, all women with pre-existing type 1 or type 2 DM should receive preconception care to optimize glycemic control (HbA1c ≤ 6%). In those cases with macrovascular or microvascular complications, family planning is even more important in order to avoid the risk of aggravation of such complications associated with a new pregnancy. The present review analyzes the metabolic and cardiovascular repercussions of hormone contraception in non-diabetic women as well as in type 1 and type 2 DM patients with and without macrovascular and microvascular complications. Finally, the recommendations pertaining to hormonal contraceptive methods for women with diabetes are summarized.

Use of oocytes that failed to be fertilized in vitro to study human sperm-oocyte interactions: comparison of sperm-oolemma and sperm-zona pellucida binding, and relationship with results of IVF

1990 ◽  
Vol 2 (6) ◽  
pp. 641 ◽  
Author(s):  
DY Liu ◽  
A Lopata ◽  
HW Baker
Keyword(s):  
Zona Pellucida ◽  
Logistic Regression Model ◽  
Sperm Concentration ◽  
Human Sperm ◽  
Fertilization In Vitro ◽  
Motile Sperm ◽  
Vitro Fertilization ◽  
Binding Ratio ◽  
Sperm Binding

A test for human sperm binding to the oolemma was developed with oocytes that failed to be fertilized in vitro. The zonae pellucidae of the oocytes were removed under a dissecting microscope by brief exposure to dilute HCl (pH 2.5-3.0) in 0.9% NaCl. The zona-free oocytes (ZFOs) were incubated with a mixture of equal numbers of motile sperm from men to be tested and fertile donors. The sperm was differentially labelled with fluorescein or rhodamine and the results expressed as a ratio of the number of test to control sperm bound to several ZFOs in order to control for variability in the ability of the oolemma to bind sperm. The number of sperm bound to the oolemma increased with time and sperm concentration. The sperm-oolemma binding ratio determined for 32 patients undergoing in vitro fertilization (IVF) was significantly correlated with the sperm-zona pellucida (ZP) binding ratio but was not correlated with other sperm tests. The sperm-oolemma binding ratio was also related to the IVF rate, but this was not significant if the sperm-ZP binding ratio was included in the logistic regression model. Only four of the 32 patients had failure of fertilization in vitro. The human sperm-oolemma binding test may be useful for studying the interaction between gametes, but the test is unlikely to be as useful clinically as the sperm-ZP binding test for predicting fertilization in vitro.

scholarly journals OPÇÕES CONTRACEPTIVAS PARA REDUÇÃO DE EVENTOS TROMBOEMBÓLICOS EM MULHERES DIABÉTICAS

2019 ◽  
Vol 6 (1) ◽  
pp. 63-69
Author(s):  
Andressa Daiana Nascimento do Carmo ◽  
Adroaldo Lunardelli
Keyword(s):  
Diabetes Mellitus ◽  
Adverse Events ◽  
Absolute Risk ◽  
Hormonal Contraception ◽  
Public Health Problem ◽  
Hormonal Contraceptive ◽  
Diabetic Patients ◽  
Thromboembolic Events ◽  
Contraceptive Methods ◽  
Combined Hormonal Contraception

Introdução: A diabetes mellitus é um grave e crescente problema de saúde pública, podendo levar à consequências irreversíveis na saúde de seus portadores, prevendo-se crescimento no número de novos portadores para os próximos anos. O uso de métodos contraceptivos hormonais também cresceu nos últimos anos, e com o retardamento das gestações, estes números tendem a aumentar ainda mais. A prescrição de contracepção hormonal para mulheres diabéticas deve ser cuidadosamente avaliada, pois a presença da doença já confere risco para eventos adversos à saúde da paciente, em especial os eventos tromboembólicos. Objetivos: O estudo objetivou revisar a literatura quanto aos métodos contraceptivos hormonais mais adequados para pacientes diabéticos, buscando redução de eventos adversos e melhora na qualidade de vida destes. Materiais e métodos: Trata-se de uma revisão integrativa da literatura onde foram acessadas as bases de dados Medline/Pubmed, ScienceDirect e Scielo. Utilizou-se os descritores contraceptive, thrombosis e diabetes, bem como a combinação destas palavras. Resultados: Foram encontrados 4 trabalhos que se enquadraram na temática do estudo e foram incluídos na revisão. Apenas 1 foi realizado exclusivamente com pacientes diabéticas. Conclusão: A utilização de contracepção hormonal combinada apresenta a mesma probabilidade de causar eventos tromboembólicos em mulheres com e sem diabetes, mas o risco absoluto em mulheres com diabetes é maior devido à doença, que é um agravante para estes incidentes. mulheres diabéticas que utilizam contracepção com estrogênio têm risco maior de desenvolver complicações trombóticas quando comparadas às que utilizam progestogênio ou as não usuárias. Palavras-chave: diabetes mellitus; anticoncepção; estrogênios; progesterona; tromboembolia. ABSTRACT Introduction: Diabetes mellitus is a serious and growing public health problem, and may lead to irreversible consequences for the health of its patients, with a projected increase in the number of new patients for the coming years. The use of hormonal contraceptive methods has also grown in recent years, and with the delay of pregnancies, these numbers tend to increase even more. The prescription of hormonal contraception for diabetic women should be carefully evaluated, since the presence of the disease already confers risk to adverse events to the patient's health, especially thromboembolic events. Objective: The present study aimed to review the literature regarding on the most appropriate hormonal contraceptive methods for diabetic patients, seeking to reduce adverse events and improve their quality’s life. Materials and Methods: It is an integrative literature review conducted by searching the databases Medline/Pubmed, ScienceDirect and Scielo. The following descriptors were used: contraceptive, thrombosis and diabetes, as well as the combination of these words. Results: Four papers were found that fit the theme of the study and were included in the review. Only 1 was performed exclusively with diabetic patients. Conclusion: Using combined hormonal contraception has the same probability of causing thromboembolic events in women with and without diabetes, but the absolute risk in women with diabetes is greater because of the disease, which is an aggravating factor for these incidents. Diabetic women who use estrogen contraception are at greater risk of developing thrombotic complications when compared to those using progestogen or non-users. Keywords: diabetes mellitus; contraception; estrogens; progesterone; thromboembolism

scholarly journals Promising Male Hormonal Contraceptive are Well Established Soon a Reality

2016 ◽  
Author(s):  
Eka R Gunardi ◽  
Arnold Soetarso ◽  
Putri Addina
Keyword(s):  
Literature Review ◽  
Contraceptive Method ◽  
Obstet Gynecol ◽  
Gnrh Antagonist ◽  
Hormonal Contraception ◽  
Hormonal Contraceptive ◽  
Clinical Use ◽  
Contraceptive Methods ◽  
Male Contraceptive

Objective: To understand the modalities used for male hormonal contraception. Methods: Literature review Conclusion: Male contraceptive methods are still limited but hormonal contraceptive methods are being developed. The basic mechanism of male hormonal contraception is to inhibit spermatogenesis by suppression of the hypothalamic-pituitary-testicular axis function. Administration of testosterone or androgen derivative that is given in combination with progestin or GnRH antagonist shows that male hormonal contraceptive is reversible, effective, and acceptable as a male contraceptive method. However, no method of male hormonal contraceptive is ready for clinical use and marketed due to limited studies. [Indones J Obstet Gynecol 2015; 3-4: 239-243] Keywords: GnRH antagonist, male hormonal contraceptive, progestin, testosterone

Contraception and thrombophilia

2009 ◽  
Vol 29 (02) ◽  
pp. 193-196 ◽  
Author(s):  
H. Rott ◽  
A. Kruempel ◽  
G. Kappert ◽  
U. Nowak-Göttl ◽  
S. Halimeh
Keyword(s):  
Chronic Illness ◽  
High Risk ◽  
Children And Adolescents ◽  
Hormonal Contraception ◽  
Hormonal Contraceptives ◽  
Thromboembolic Events ◽  
Contraceptive Methods ◽  
Secondary Complications ◽  
Increased Risk ◽  
Coagulation Proteins

SummaryThe risk of thromboembolic events (TE) is increased by acquired or inherited thrombo -philias (IT). We know that some hormonal contraceptives also increase the risk of thrombosis, thus, the use of such contraceptives are discussed as contraindications in women with IT. TEs are infrequent events in children and adolescents and in the majority of cases are associated with secondary complications from underlying chronic illness. Although adolescents are not typically considered to be at high-risk for TE, this cohort is frequently using hormonal contraception, leading to an increased risk in cases with unknown IT. The risk of TE with pregnancy alone is higher than associated with combined hormonal contra -ception. Progestin-only methods have not been found to increase the risk of TE with only moderate changes of coagulation proteins compared to normal reference values. Conclusion: Thrombophilic women are good candidates for progestin-only contraceptive methods.

scholarly journals Clinical features of migraine with onset prior to or during start of combined hormonal contraception: a prospective cohort study

2021 ◽  
Author(s):  
Gabriele S. Merki-Feld ◽  
Peter S. Sandor ◽  
Rossella E. Nappi ◽  
Heiko Pohl ◽  
Christoph Schankin
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Hormonal Contraception ◽  
Hormonal Contraceptive ◽  
Natural Cycle ◽  
Free Interval ◽  
Migraine Frequency ◽  
Combined Hormonal Contraception ◽  
Migraine Onset

AbstractMany studies have described the features of menstrually related migraines but there is a lack of knowledge regarding the features of migraine in combined hormonal contraceptive users (CHC). Hormone-withdrawal migraines in the pill-free period could differ from those in the natural cycle. Gynaecologic comorbidities, like dysmenorrhea and endometriosis, but also depression or a family history might modify the course of migraine. A better understanding of migraine features linked to special hormonal situations could improve treatment. For this prospective cohort study, we conducted telephone interviews with women using a CHC and reporting withdrawal migraine to collect information on migraine frequency, intensity, triggers, symptoms, pain medication, gynaecologic history and comorbidities (n = 48). A subset of women agreed to also document their migraines in prospective diaries. The mean number of migraine days per cycle was 4.2 (± 2.7). Around 50% of these migraines occurred during the hormone-free interval. Migraine frequency was significantly higher in women who suffered from migraine before CHC start (5.0 ± 3.1) (n = 22) in comparison to those with migraine onset after CHC start (3.5 ± 2.1) (n = 26). Menstrually related attacks were described as more painful (57.5%), especially in women with migraine onset before CHC use (72%) (p < 0.02). Comorbidities were rare, except dysmenorrhea. The majority of migraine attacks in CHC users occur during the hormone-free interval. Similar as in the natural cycle, hormone-withdrawal migraines in CHC users are very intense and the response to acute medication is less good, especially in those women, who developed migraine before CHC use.

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