Phytochemical and biological assessments on Lipidium meyenii [maca] and Epimidium sagittatum [horny goat weed]

The effects of Lipidium meyenii [maca, LM] and Epimidium sagittatum [horny goat weed, ES] have been investigated due to their involvement in fertilization. Both of the drugs showed good results before, during and after fertilization in male and female mice. The results revealed that the crude extract of Lipidium meyenii caused a significant decrease in the no. of writhes at 300 and 500mg/kg [p<0.05] as compare to control, Epimidium sagittatum and standard drug. The gross behavioral, open field, exploratory behaviour, forced swimming test for stress, diuretic activity, chronic toxicity with the effect on reproduction of both male and female and change in body weight were also studied. The phytochemical study showed the presence of tannin, alkaloid, carbohydrate, rich protein and absence of sterol in LM, whereas ES shows presence of sterol and less protein. LS improve in muscle activity and exploratory behaviours without any toxic effects on mice and their pups. It does not have diuretic effect for first two hour but act normally after initial phase of drug therapy. Epimidium sagittatum has dual action that is at low dose it has slight stimulation action and at high dose little depressive effect. ES also has some diuretic effect. Overall these results suggest that LM is highly effective remedy for treatment of impotency and reduces stress and depression, because of dual effect ES not only suggested as an anxiolytic medicine but also effective in female hormonal disorder

Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate

CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.

Efficacy, efficiency and effectiveness of gonadotropin therapy for infertility treatment / Eficácia, eficiência e efetividade da terapia gonadotrófica para o tratamento da infertilidade

Gonadotropin therapy is an essential element in infertility treatments involving assisted reproductive technology. In recent years there have been outstanding advances in the development of new gonadotropins, particularly with the production of gonadotropins using biotechnological resources. Recombinant gonadotropins have higher specific activity compared with urinary counterparts, thus allowing subcutaneous administration of minimal amounts of glycoprotein. As a result, recombinant formulations have a better safety profile despite an overall similarity in terms of efficacy for pregnancy, as reported in many randomized controlled trials and meta-analyses. Gonadotropins stimulate the ovaries to develop follicles and oocytes, which are the raw material for fertilization and embryo production. The resulting embryos are transferred (fresh or frozen-thawed) to achieve pregnancy. The efficiency of a gonadotropin should therefore measured by the amount of drug used, the number of oocytes/embryos produced, and the number of pregnancies achieved by transferring fresh and/or frozen-thawed embryos to the uterus (cumulative pregnancy). Comparisons between different gonadotropin preparations should also take into account other important quality indicators in reproductive medicine, such as safety and patient-centeredeness. Altogether, the aforementioned quality indicators favor biotech gonadotropins over biologic products in infertility therapy.

RESUMO A terapia gonadotrófica é elemento essencial nos tratamentos de infertilidade que envolvem tecnologia de reprodução assistida. Nos últimos anos houve avanços notáveis no desenvolvimento de novas gonadotrofinas, principalmente com a produção de gonadotrofinas via recursos biotecnológicos. As gonadotrofinas recombinantes têm maior actividade específica em comparação com os suas homólogas urinárias, permitindo, assim, a administração subcutânea de quantidades mínimas de glicoproteína. Como resultado, as formulações recombinantes tem um melhor perfil de segurança, apesar de semelhança em termos de eficácia para a gravidez, como relatado em diversos ensaios clínicos randomizados e meta-análises. As gonadotrofinas estimulam os ovários a desenvolver folículos e ovócitos, que são a matéria-prima para a fertilização e produção de embriões. Os embriões resultantes são transferidos (frescos ou congelados/descongelados) para produzir gravidez. Comparações entre as gonadotrofinas devem, portanto, ser medidas não somente pela eficácia clínica de produzir gravidezes pela transferência de embriões a fresco, mas sobremaneira pela eficiência na produção de ovócitos e embriões em relação à quantidade de droga administrada, e efetividade na obtenção de gravidezes pela transferência de embriões frescos e congelados/descongelados (taxa de gravidez cumulativa). As comparações entre diferentes preparações de gonadotrofinas também devem levar em conta outros indicadores importantes de qualidade em medicina reprodutiva, como a segurança e o interesse do paciente. Estes indicadores de qualidade favorecem as gonadotrofinas biotecnológicas em relação aos produtos biológicos na terapia da infertilidade.

Comparing of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles

Clomiphene citrate [CC] an agonist and antagonist of estrogen, is the first line treatment in ovarian stimulation. Anti-estrogenic effect of CC in endometrial thickness and cervical mucus has negative effect on pregnancy rate. Letrozole is an Aromatase Inhibitor has been seen that has acceptable pregnancy rate compared to CC. The aim of this study was to compare the efficacy of letrozole and clomiphene citrate [CC] with gonadotropins for ovarian stimulation in women candidate for intrauterine insemination [IUI]. One hundred sixty patients eligible to IUI therapy enrolled in this study. Patients randomized to two groups: group A [received letrozole-gonadotropin] and group B [received CC-gonadotropin]. In group A [n=80] letrozole was given on days 3-7 of the menstrual cycles. In group B clomiphen citrate was given like letrozole combined with human menopausal gonadotropin [hMG] administered every day starting on day 8. Ovulation was triggered with urinary HCG when the leading follicle [s] reached 18 mm in diameter. A single IUI was performed 36-40 hours later. The ovarian stimulation response [E[2] levels and number of follicles, clinical pregnancy and endometrial thickness] was primary outcome. Both groups were similar in demographic characteristics. There was a significantly lower peak serum E[2] level in the letrozole group compared with CC. [236 +/- 86 Vs. 283 +/- 106 pg/mL, respectively; p<0.002]. The number of mature [>18 mm] preovulatory follicles was significantly higher in CC group than letrozole group [2.2 +/- .68 Vs. 2.02 +/- 0.63 respectively; p=0.025]. Endometrial thickness measured at the time of hCG administration was significantly higher in letrozole group. [9.08 +/- 1.2 mm Vs. 8.1 +/- 1.9 mm; p=0.0001]. The clinical pregnancy rate was comparable between two groups. Letrozole is a good and cost-effective alternative to CC in IUI cycles

Síndrome do ovário policístico: aspectos atuais das abordagens terapêuticas: parte 2 / Polycystic ovary syndrome: current aspects of the therapeutic interventions: part 2

A segunda parte desta revisão inclui as demais opções de tratamento da síndrome do ovário policístico (SOP). O citrato de clomifeno (CC) é utilizado na dose de 50 a 200 mg/dia durante cinco dias a partir do segundo ao quinto dia do ciclo menstrual. A taxa de ovulação após o tratamento com CC é de aproximadamente 73 por cento e a de gravidez em torno de 36 por cento. Com os análogos do GnRH ocorre redução dos níveis de gonadotrofinas e diminuição da secreção de estrógenos e androgênios. O principal risco da estimulação com gonadotrofinas é a gestação múltipla. Anastrazole e letrozole pertencem à classe dos inibidores da aromatase de terceira geração. As taxas de ovulação e gestação com letrozole variam de 54,5 a 82,4 por cento e 9 a 25 por cento, respectivamente. Não ocorreu diferença significativa nas taxas de ovulação e gestação entre o uso de 2,5 mg de letrozole em comparação com 1 mg de anatrozole. O uso da N-acetilcisteína (NAC) sugere melhora significativa da sensibilidade à insulina em mulheres com SOP. Os contraceptivos hormonais orais combinados permanecem como tratamento predominante para redução do hiperandrogenismo e das irregularidades menstruais em mulheres que não desejam engravidar. Os antiandrógenos são utilizados principalmente para diminuir as queixas de hirsutismo e o efeito será percebido em 9 a 12 meses de tratamento. Muitas mulheres se submetem à cauterização ovariana ou a laser por videolaparoscopia tendo restauração espontânea da ovulação com gravidez subsequente. Porém, os benefícios potenciais destas intervenções tendem a ser atenuados devido à formação de aderências.

The second part of this review includes other treatment options for polycystic ovary syndrome (PCOS). The clomiphene citrate (CC) is used in a dose of 50 to 200 mg/day for five days, begining from the second to fifth day or the menstrual cycle. The ovulation rate after the treatment with CC is approximately 73 percent and the pregnancy rate is about 36 percent. With GnRH analogues, there is a reduction in gonadotrophin levels and a decrease of androgen and estrogen secretion. The major risk due to stimulation with gonadotrophins is the multiple gestation. Anastrozole and letrozole belong to the class of third-generation aromatase inhibitors. The rates of ovulation and pregnancy with letrozole vary from 54.5 to 82.4 percent and from 9 to 25 percent, respectively. There was no significant difference in ovulation and pregnancy rates with the use of 2.5 mg of letrozole compared to 1 mg of anastrozole. The use of N-acetyl Cysteine (NAC) suggests significant improvement in insulin sensibility in women with PCOS. The combined oral hormonal contraceptives are still the predominant treatment to decrease hyperandrogenism and menstrual irregularities in women who do not want to get pregnant. Anti-androgens are used mainly to diminish complaints of hirsutism and the effect will be noted after 9 to 12 months of treatment. Several women undergo ovarian cauterization of with laser by videolaparoscopy having their ovulation spontaneously restored with subsequent pregnancy. However, the potential benefits of these interventions might be attenuated due to adhesion formations.

Cause of infertility and response to ovulation induction drugs -a hospital based study

This study was performed to investigate the most common causes of infertility and the choice of the more suitable and more easily achievable treatment. A detail history and physical examination were done for all the patients who were referred to Mahdishahr Hospital with chief complaint of infertility from October 2004 to September 2005. Patients who failed to become pregnant after unprotected intercourse for 1 year were chosen as the criteria for to this study. At first semen analysis was performed for all couples. Among the patients who were complaining of oligomenorrhea, galactorrhea or in their laboratory test hyperprolactinemia was found, the treatment started with ovulation induction drugs. In all these groups of patients endometrial thickness and the size of follicles was measured by sonography in the 13th days of their period, among the patients with two or four follicles bigger or equal to 18 mm [If they were treated with clomiphene citrate, bromocriptine or dexamethasone] or when two or four follicles were bigger or equal to 16 mm [if they were treated with Human Menopausal Gonadotropin [HMG] and endometrial thickness or equal to 6mm and Human Chorionic Gonadotropin [HCG] Ampoule [10000 unit] was injected. All these patients were followed to control their response to the treatment and during the whole period of pregnancy. In the other patients hystrosalpingography or post-coital test used for finding the cause of infertility. In 57% of the patients [40 persons] there were symptoms of oligomenorrhea, galactorrhea or hyperprolactinemia. For these patients ovulation induction is started by clomiphene citrate, bromocriptine, dexamethasone and HMG. 27 cases [67%] of them conceived. Term pregnancy with normal child in 20 cases, abortion in 5 cases and unexpected preterm birth both in 21 weeks of pregnancy happened. Twenty eight percent [20 cases] of cause of infertility was male factor. 7% [5 cases] and 1/4% [lease] of causes were tubal and cervical factors respectively. It's concluded that the most common cause of infertility in Mahdishahr is the ovulatory factor. Other causes respectively are male-factor, tubal, cervical, and other factors. Besides, in a large percent of these patients who were treated by ovulation induction pregnancy happend which is noticeable

Plantas altoandinas y su efecto sobre la fertilidad: ¿mito o realidad? / High andes plants and their effect on fertility: myth or reality?

Se realizó una recopilación de información técnica y científica relativa a Lepidium meyenii Chacón (Maca), una planta de la familia Brassicaceae que crece en Los Andes Centrales del Perú, entre los 4.000 y 4.500 msnm. Maca ha sido tradicionalmente empleada en la región altoandina debido a supuestas propiedades afrodisíacas y como estimulante de la actividad reproductiva en el hombre y sus animales. Comparativamente con otros vegetales, el análisis químico de la raíz demuestra un alto contenido de carbohidratos, proteínas, lípidos, vitaminas y minerales. Adicionalmente, aminoácidos esenciales y esteroles de alta especificidad que forman parte de neurotransmisores y hormonas, que a su vez cumplen un importante rol funcional en la actividad reproductiva de los mamíferos, se encuentran en alta concentración. Se concluye, a partir de los datos experimentales logrados por variados autores, que el valor nutricional y el efecto sinérgico de los constituyentes naturales de Lepidium meyenii (Maca) deben ser considerados para explicar su acción preventiva de los efectos deletéreos de la altitud sobre la espermatogénesis y estimulante de la fertilidad en sus variados componentes.

The oral contraceptive pill effectively permits cycle batching for an intermittent in vitro fertilization programme in Trinidad and Tobago / Las Píldoras Anticonceptivas Orales Permiten la Agrupación Eficaz de los Ciclos para un Programa Intermitente de FIV en Trinidad y Tobago

Assisted reproductive technology (ART) in small island states like Trinidad and Tobago is usually provided in batches so as to minimize the cost of providing the service. As a result, patients 'cycles have to be synchronized in order to coincide with the arrival of a visiting embryologist. This is a retrospective study which evaluates the experience of pre-treatment with an oral contraceptive pill (OCP) as a means of batching cycles for an intermittent ART programme. Seventy-four in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles in which OCP usage was employed (Group A), were compared with 121 cycles which did not require pharmaceutical manipulation (Group B). In both groups more than 50 of women were older than 36-years. Two cycles were cancelled in Group A and seven in Group B, because of poor ovarian response. Although the pregnancy rate per treatment cycle was higher in Group A than in Group B (26.3 vs 17.3), this difference was not significant. More spontaneous miscarriages occurred in the non-OCP women and ovarian cyst formation was more common in these women. The authors experience indicates that the OCP is a simple, cheap and efficient means of batching patients for an intermittent ART programme and can be utilized in other small ART centres

La tecnología de reproducción asistida (TRA) en los pequeños estados insulares como Trinidad y Tobago, usualmente se ofrece por tandas a fin de minimizar los costos del servicio brindado. En consecuencia, los ciclos de las pacientes tienen que ser sincronizados de modo que coincidan con la visita del embriólogo. Éste es un estudio retrospectivo que evalúa la experiencia del pretratamiento con píldoras anticonceptivas orales (PAO) como medio de agrupar los ciclos con el propósito de organizar un programa intermitente de TRA. Setenta y cuatro ciclos de fertilización in vitro (FIV) e inyección intracitoplasmática de esperma (ICSI) en los que se recurrió al uso de PAO (Grupo A), fueron comparados con 121 ciclos que no requirieron manipulación farmacéutica (Grupo B). En ambos grupos, > 50% de las mujeres tenían más de 36 años de edad. Dos ciclos fueron cancelados en el grupo A y siete en el grupo B, debido a una respuesta ovárica pobre. Aunque la tasa de embarazo por ciclo de tratamiento fue más alta en el grupo A que en el grupo B (26.3% vs. 17.3%), esta diferencia no fue significativa. El número de abortos espontáneos fue mayor y la formación de quistes ováricos más común, en las mujeres que tomaron PAO. La experiencia de los autores indica que la PAO es un medio simple, económico y eficaz de agrupar a los pacientes en un programa intermitente de TRA, y puede utilizarse en otros centros pequeños de TRA.

A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene.

BACKGROUND & OBJECTIVES: Despite its wide use, the benefits of intrauterine insemination (IUI), its over timed intercourse (TI) in couples with unexplained infertility is a matter of debate. Studies in Indian couples with unexplained infertility showing benefit of IUI over TI are not available. The present study was done with the objective of comparing TI and IUI with husband's sperm in couples with unexplained infertility undergoing superovulation with clomiphene. METHODS: A total of 140 couples with unexplained infertility were subjected to controlled ovarian hyperstimulation (COH) with clomiphene and prospectively randomized to receive either TI (group A) or IUI (group B). Complete follow up was available for 113 couples only. RESULTS: The pregnancy rate and cycle fecundity rate after COH/TI was 41 and 8.8 per cent and after COH/IUI 18 and 3.4 per cent respectively. The difference was statistically not significant. INTERPRETATION & CONCLUSION: The findings of the present study showed that in women with unexplained infertility addition of IUI to ovulation induction does not improve conception rates. COH/TI can help to achieve good results and save the expense and discomfort due to a invasive procedure.

La sterilite du couple

Dans le cadre de l'emission science et sante produite par la Radio Nationale du Zaire; le Docteur Antoine Mosikwa a ete invite pour developper le probleme de sterilite du couple. Ce texte est donc la traduction de son experience. Il met l'accent sur la sterilite feminine. Il ressort de ses reponses que les causes de cette sterilite sont generalement tubaires; ovariennes; cervicales et uterines

Causes et traitements classiques

La sterilite et la sous-fecondite constituent en Afrique une preoccupation majeure aussi bien au niveau des formations sanitaires que dans le contexte socio-economique. Plusieurs causes peuvent etre a l'origine de cette situation. Mais l'un des principaux facteurs demeure la sterilite tubaire. Bien que les causes de la sterilite et de la sous-fecondite soient connues; les traitements ne sont pas souvent a la portee de l'Africain moyen