Use Of Desogestrel Research Articles

P-694 Desogestrel did not affect Follicular Output Rate (FORT) during controlled ovarian stimulation for oocyte vitrification: prospective cohort study

Abstract Study question Does desogestrel an option for LH suppression during controlled ovarian stimulation for oocyte vitrification? Summary answer This new option for LH suppression did not affect FORT and, consequently, the number of collected oocytes for vitrification. What is known already Traditionally, LH suppression is achieved by using a gonadotropin-releasing hormone (GnRH) analogue. However, improved cryopreservation techniques and freeze-all strategies are introducing new concepts, including the possibility of using progesterone instead of GnRH analogues. Progesterone compounds are currently wide-used during ovarian stimulation for oocyte freezing for LH suppression. The use of oral medroxyprogesterone was previously shown to effectively prevent the LH surge, without impacting embryo development or pregnancy rates after frozen embryo transfer. The use of dydrogesterone with the same purpose was also effective. Desogestrel is a progesterone broadly known and accepted, and has good tolerability and low cost. Study design, size, duration A prospective cohort study was performed during the period of 2019-2021 including 75 patients submitted to oocyte freezing and 173 women matched by age as the controls (patients submitted to IVF for the first time). Participants/materials, setting, methods Patients from the control group used a flexible GnRH antagonist for LH suppression, and patients in the desogestrel group utilized desogestrel 75 mcg oral twice a day (starting from the beginning of gonadotropin to hCG/agonist day). All patients received the same gonadotropin regimen (recombinant FSH). The final oocyte maturation was equal for both groups (recombinant hCG and GnRH analogue agonist). The primary endpoint was the antral follicle responsiveness to follicle-stimulating hormone, measured by FORT. Main results and the role of chance Age [control group= 36 years (median 28-45); desogestrel group= 36 years (median 23-43); p = 0.793; Mann Whitney U test], baseline antral follicle count [control group= 8 (2-23); desogestrel group= 9 (2-21); p = 0.741; Mann Whitney U test] and anti-Mullerian hormone [control group= 1.5 (0.05-7.95); desogestrel group= 1.00 (0.01-16.00); p = 0.540; Mann Whitney U test] were similar between both groups. However, the controlled ovarian stimulation length was shorter in the control group [10.4±1.6 vs. 11.0±1.6; p = 0.044; t-student test,] and those patients utilized less gonadotropin than the desogestrel group [2736 UI ± 745 vs. 2933 UI ± 785; p = 0.047; t-student test,]. Finally, Follicular Output Rate (FORT) [control group= 45%; desogestrel group= 52%; p = 0.217; t-student test], number of collected oocytes [control group= 6 (1-33); desogestrel group= 8 (1-20); p = 0.293; Mann Whitney U test] and MII [control group= 5 (1-27); desogestrel group= 6 (1-19); p = 0.156, Mann Whitney U test] were the same between both groups. Limitations, reasons for caution The small sample size and the absence of randomization are the main limitations of our study. Since the first results were encouraging, a randomized study should be performed. Wider implications of the findings Desogestrel is a cheap and easy option to be used during controlled ovarian stimulation for oocyte vitrification, since the final results are the same. This is the first scientific report showing the use of desogestrel did not affect FORT and, consequently, the number of collected oocytes for vitrification. Trial registration number Not applicable

P-636 Use of Desogestrel as an alternative to GnRH antagonists to inhibit the LH surge: a prospective randomized controlled observational study

Abstract Study question To describe whether desogestrel is as effective as GnRH antagonists in inhibiting the LH surge during controlled ovarian stimulation. Summary answer We conclude that although we can obtain fewer oocytes,desogestrel is effective as GnRH antagonists to inhibit the LH surge during controlled ovarian stimulation. What is known already It is known that ovarian secretion of progesterone has the ability to modulate the secretory pattern of LH of a natural menstrual cycle. Because exposure to high levels of progesterone can generate a phase shift between embryonic development and endometrial receptivity, this was not an option when performing HOC in conventional IVF-ICSI. New technologies and constant advances in vitrification techniques for both gametes and embryos have allowed us to think of different strategies when performing a HOC. This is why a new concept, progestagen priming, was introduced as a safe and comparable alternative to conventional ovarian stimulation with GnRH antagonists. Study design, size, duration We conducted a prospective, observational, randomized, controlled study at our institution IFER affiliated with the University of Buenos Aires, from August 2020 to December 2021. A total of 74 patients were included. Our main objective was to evaluate the efficacy of desogestrel as an LH surge inhibitor in patients undergoing egg donation, medical and social fertility preservation, and controlled ovarian stimulation without fresh embryo transfer. Participants/materials, setting, methods Patients under 39 years of age who underwent controlled ovarian stimulation for egg donation cycles, fertility preservation for medical and social reasons, and IVF-ICSI cycles without fresh transfer (risk of OH,PGS) The patients were separated into two groups. Both groups received conventional HOC.In the DESOGESTREL group received 75mg/day from the start of stimulation to the day of CGH, in the control group, received antagonists 0.25mg/day with follicles 14 mm until the day of CGH.ther parameters Main results and the role of chance We divided the Desogestrel Goup : > 35-35 y (GI) 32 p, 36-39 y (GII) 42p, Control Group : 35-35 y (GIII) 29 p,36-39 y (GIV) 45p. total dose of gonadotrophins used: GI: 1600 UI ± 300 UI, GIII: 1800 UI ± 400 UI ( NS) GII:1900 UI ± 400 UI, G IV : 2200 UI ± 400 UI (NS).Length of HOC: G I: 12 d ± 2 , G III: 13 d ± 2, G II: 14 d ± 2 , G IV: 15 d ± 2 ( NS). MII retrieved: GI: 10 ±3, GIII: 12± 3 (NS), GII : 7± 3, G IV: 7± 2 ( NS).The number of oocytes obtained may be a little lower than those obtained in the control group, but not statistically significant, the same as in the number of doses of gonadotrophins used, nor in the number of days of stimulation. Limitations, reasons for caution Size of study group Wider implications of the findings Although the study group is small, we have shown that the use of desogestrel is similar shown with the use of other gestagens during COH. We believe that desogestrel is a patient-friendly alternative due to its route of administration, price, and longer half-life, compared to antagonist analogs. Trial registration number NA

Desogestrel-only contraception may reduce headache frequency and improve quality of life in women suffering from migraine

Objective To analyse the effects of a three-month course of progestogen-only contraception with desogestrel 75 μg on disability, headache frequency and headache intensity in migraineurs.Materials and methods Migraine disability headache questionnaires (MIDAS) were collected from 37 migraineurs during counselling, and at the end of three months treatment with desogestrel. Another ten women initiated but did not complete treatment. They are included in the overall evaluations of the effect of the regimen on migraine status.Results Desogestrel was associated with significant reductions in headache days and intensity (p < 0.001; p < 0.006), and a significant improvement in quality of life. Days missed at work and days missing leisure activities diminished (p < 0.001; p < 0.001). The MIDAS migraine disability score improved significantly (from 27.4 to 11.1 points) (p < 0.001). While 25 of the 37 women (68%) experienced a decrease of at least one grade, this level of benefit cannot be extrapolated to all initiators. When dropouts are considered, MIDAS grades decrease in 53% (25/47) of the cases.Conclusion The majority of migraineurs experienced a clinically significant reduction in headache frequency and improvement of quality of life with use of desogestrel. Prospective randomised controlled trials are needed to substantiate our results.

Kontrazeption bei Frauen mit Migräne

BackgroundMigraine is a complex, disabling neurological condition characterized by recurrent episodes of headache. It affects up to 15 % of the adult population, whereby women of reproductive age are more frequently affected than men. Estrogens have been shown to play a pivotal role in migraine pathophysiology. Migraineurs are at increased for cerebral stroke and migraine is associated with an elevated risk for cardiovascular events. This risk has been shown to be especially high in migraine with aura. Contraception should not expose migraineurs to further health risks.Contraception using gestagensIn contrast to combined hormonal contraceptives (CHC), progestin-only contraceptives (POC) are not associated with an elevated risk for ischemic attacks. Preliminary data even demonstrate the reduction of monthly migraine days, auras and use of analgetics with the use of desogestrel 75 μg.Other methodsCHC should only be used in exceptional cases. Migraine with aura is an absolute contraindication. Copper-releasing intrauterine devices do not affect the course of migraine. Hormone-withdrawal migraines can sometimes be successfully treated with use of CHC in a continuous regime. However, the affect of this therapy on the risk for ischemic attacks and ischemic stroke remains unclear; therefore, gestagens represent the preferred approach.

Headache frequency and intensity in female migraineurs using desogestrel-only contraception: A retrospective pilot diary study

Migraine seems to be substantially related to hormonal changes. However, migraine, but also the use of combined oral contraceptives (COC), is associated with an increased risk for vascular events. Therefore progestagen-only contraception is an important alternative to combined preparations. Clinical observations and one pilot study demonstrate that the use of desogestrel 75 µg may have a positive impact on migraine. The aim of this retrospective analysis of prospectively collected headache diaries was to study the effect of desogestrel 75 µg on headache frequency, intensity and use of acute medication in premenopausal women with migraine in a clinical setting. Patients' charts were included from women who wanted to use desogestrel 75 µg as a contraceptive and had kept headache diaries over six months (three months pretreatment and three months during treatment). Out of 58 women, 38 women had completed headache diaries for this period. Incomplete diaries ( N = 12), side effects ( N = 5) and loss to follow-up ( N = 3) were the reasons for the exclusion of 20 women. The three months (total of 90 days) before and after initiation of the progestin were compared. Days with migraine (5.2 vs. 3.7), days with all kind of headache (8.3 vs. 6.5) and days with use of any headache medication (5.7 vs. 3.5) were significantly reduced at follow-up after three months. In addition there was a reduction in headache intensity ( P < 0.0001). The reduction in number of days with use of triptans was not significant ( P < 0.14). In the 38/58 migraineurs with complete diaries there was a statistically significant decrease in migraine days, headache intensity and medication use. Tension-type headache days decreased but were not significant. Our preliminary data are promising, but should be interpreted cautiously because they were obtained in a small population of women visiting a specialty hormone and migraine clinic. Randomised controlled trials need to be conducted to substantiate our results.

Is letrozole affecting the beneficial changes of desogestrel at the endometrial level in patients with endometriosis?

OBJECTIVE: Cell proliferation is increased and apoptosis is diminished in eutopic endometrium from patients with endometriosis (EDT), factors that may contribute to its etiopathogenesis. We previously described the reversal of those findings with the use of desogestrel (Meresman et al, 2005). In patients with EDT treated with aromatase inhibitors, a progestin is also administered in order to block the release of gonadotropins (Ailawadi et al, 2004). In the present study, we evaluated and compared the endometrial effects of treatment with desogestrel and a combination of letrozole and desogestrel on these parameters in patients with histologically proven EDT.DESIGN: Apoptosis and cell proliferation were evaluated in eutopic endometrial tissue from EDT patients.MATERIALS AND METHODS: 10 EDT patients had an endometrial biopsy before treatment, after 6 weeks of desogestrel 75 μg/day (treatment D) and then, after another 6 weeks of a combination of desogestrel 75 μg + letrozole 2.5 mg/day (treatment DL). The lesions were then fixed and stained with hematoxylin-eosin for histological analysis. Cell proliferation was assessed by PCNA immunohistochemistry before and after treatments. Determination of apoptosis was done in the same tissue by the TUNEL assay.RESULTS: PCNA index was assessed in eutopic endometrium from EDT patients before treatment and observed 36.08±4.8% positive cells. After treatment D, cell proliferation was significantly suppressed to 12.36±2.8% positive cells (p<0.01). Similarly, the treatment DL caused a significant decrease in cell proliferation to 14.71±3.9% positive cells (p<0.01). Likewise, both treatments significantly increased apoptosis in eutopic endometrium from EDT patients from 2.49±0.6% apoptotic cells (APc) before treatment to 12.98±2.1% APc after desogestrel administration (p<0.01) and to 12.2±3.7% APc after the combined treatment (p<0.01). Histologically, under treatment D the endometrial glands and the stroma showed discrepancy, with a more advanced stroma, highlighted by progestational changes and minimal proliferation, while under treatment DL both endometrial components showed advanced progestational changes and complete absence of endometrial proliferation.CONCLUSIONS: Desogestrel and the combination of letrozole and desogestrel significantly diminished cell proliferation and induced apoptosis in eutopic endometrial tissue from EDT patients. These data may have clinical relevance in the treatment of EDT. OBJECTIVE: Cell proliferation is increased and apoptosis is diminished in eutopic endometrium from patients with endometriosis (EDT), factors that may contribute to its etiopathogenesis. We previously described the reversal of those findings with the use of desogestrel (Meresman et al, 2005). In patients with EDT treated with aromatase inhibitors, a progestin is also administered in order to block the release of gonadotropins (Ailawadi et al, 2004). In the present study, we evaluated and compared the endometrial effects of treatment with desogestrel and a combination of letrozole and desogestrel on these parameters in patients with histologically proven EDT. DESIGN: Apoptosis and cell proliferation were evaluated in eutopic endometrial tissue from EDT patients. MATERIALS AND METHODS: 10 EDT patients had an endometrial biopsy before treatment, after 6 weeks of desogestrel 75 μg/day (treatment D) and then, after another 6 weeks of a combination of desogestrel 75 μg + letrozole 2.5 mg/day (treatment DL). The lesions were then fixed and stained with hematoxylin-eosin for histological analysis. Cell proliferation was assessed by PCNA immunohistochemistry before and after treatments. Determination of apoptosis was done in the same tissue by the TUNEL assay. RESULTS: PCNA index was assessed in eutopic endometrium from EDT patients before treatment and observed 36.08±4.8% positive cells. After treatment D, cell proliferation was significantly suppressed to 12.36±2.8% positive cells (p<0.01). Similarly, the treatment DL caused a significant decrease in cell proliferation to 14.71±3.9% positive cells (p<0.01). Likewise, both treatments significantly increased apoptosis in eutopic endometrium from EDT patients from 2.49±0.6% apoptotic cells (APc) before treatment to 12.98±2.1% APc after desogestrel administration (p<0.01) and to 12.2±3.7% APc after the combined treatment (p<0.01). Histologically, under treatment D the endometrial glands and the stroma showed discrepancy, with a more advanced stroma, highlighted by progestational changes and minimal proliferation, while under treatment DL both endometrial components showed advanced progestational changes and complete absence of endometrial proliferation. CONCLUSIONS: Desogestrel and the combination of letrozole and desogestrel significantly diminished cell proliferation and induced apoptosis in eutopic endometrial tissue from EDT patients. These data may have clinical relevance in the treatment of EDT.

Does the pill make a difference? Previous maternal use of contraceptive pills and allergic diseases among offspring

Maternal use of oral contraceptive pills (OCPs) might increase the prevalence of allergic diseases among offspring. The aim of the study was to clarify if there are differences between OCP types in this association. Primary outcomes were asthma, allergic rhinitis and atopic eczema among 1182 children (618 asthmatic and 564 controls) aged 5-6 years. Maternal previous use of desogestrel, gestodene or cyproterone acetate before pregnancy, each combined with ethinyloestradiol (EO), increased the risk of allergic rhinitis among offspring compared with those children whose mothers had not used OCPs (OR 1.67, 95% CI 1.07-2.59, P < 0.024), and this risk was increased mainly in those children with parental allergy (OR 1.78, 95% CI 1.11-2.86, P < 0.018), especially in boys (OR 2.12, 95% CI 1.17-3.84, P < 0.014). No associations were observed between maternal use of OCPs before pregnancy and asthma or atopic eczema among offspring. The association between the previous use of OCPs and allergic rhinitis was not mediated through maternal sex steroid levels during early pregnancy, but women who had used more androgenic types of progestin formulas had higher serum levels of progesterone during early pregnancy. Maternal previous use of desogestrel, gestodene or cyproterone acetate before pregnancy, each combined with EO, increased the risk of allergic rhinitis among offspring compared with those children whose mothers had not used OCPs and this risk was detected mainly in boys and in children with parental allergy.

EVOLUCIÓN A UN AÑO DE LOS EFECTOS ADVERSOS, EN UNA COHORTE DE PACIENTES CON IMPLANTE SUBDÉRMICO DE DESOGESTREL

SUMMARY Objective: To determine the adverse effects of implants subskin of desogestrel. Method: A descriptive longitudinal study was made in a cohort carrying patients of implants that they had as minimum three months of use, previous informed consent were included in the study. Four measurements were made in quarterly form, registering the most frequent effects, referred by the patient. It was used descriptive statistic and confidence intervals. Results: It was study 50 patients. The presented effects with greater percentage in the first trimester were: alterations of cycle 48%, mastalgia 46%, amenorrhoea 40%, dizzies 40%, headache 40%, nauseas 30%, acne 28%, increase of weight 26% and local pain 10%. It was observed at the end of the third quarterly reduction of the statistically significant effects of the headache, mastalgia, dizzies (p<0.05), for the fourth trimester nauseas and alterations of the cycle (p<0.05). The 11.1% of the patients deserted of the method at the end of the study. It was observed that the use of desogestrel had a significant statistic for the control of the dismenorrea with p< 0.05 at the end of the fourth trimester of use. Conclusions: You implant them of desogestrel have adverse effects important in the first’s months of use to diminish most of them at the end of the first year.

Venous Thromboembolism and Oral Contraceptives

Recent studies of currently available oral contraceptives indicate that the risk of major sequelae is low in young women (aged between 20 and 24 years). Venous thromboembolism remains one event that can occur in users independent of the presence of risk factors. However, the attributable risk is small, with a range of approximately 7 to 18 events per 100 000 women annually. This risk is directly proportional to estrogen dosage starting at levels of 30-35 microg. The type of progestogen (progestin) may also influence risk, though recent studies are controversial. In particular, there is debate surrounding whether desogestrel and gestodene carry a greater risk of thromboembolism than levonorgestrel. Modifiable risk factors for venous thromboembolism include hemostatic disorders, especially factor V Leiden, and possibly obesity. Cigarette smoking is not a significant risk factor in oral contraceptive users. With the exception of avoiding oral contraceptive use among women with a either a personal history of venous thromboembolism or a strong family history (until evaluated for hemostatic abnormalities), and perhaps limiting the use of desogestrel- or gestodene-containing oral contraceptives, there is little clinicians can do to reduce the risk of this disorder.

Comparative study of the effects of a progestogen-only pill containing desogestrel and an intrauterine contraceptive device in lactating women

Objective To evaluate the effects of desogestrel 75μg/day, as a progestogen-only pill compared with a copper-bearing intrauterine contraceptive device (IUCD) on lactation and to study the safety of both treatments in mothers and children. Transfer of etonogestrel to breast milk was studied in a subgroup of desogestrel users. The children were to be followed up until 2.5 years of age. Design An open, non-randomised, group-comparative study in lactating women. Setting University Hospital, Reykjavik, Iceland. Participants A total of 83 lactating women; 42 received desogestrel and 41 had an IUCD inserted for seven consecutive treatment cycles of 28 days. Methods Evaluation visits were planned at baseline and at the end of treatment cycles 1, 4 and 7. The amount of breast milk was determined by weighing the infants before and after feeding, at baseline and after treatment cycles 1 and 4. Milk samples were obtained at the same time for constituent measurements. Safety was studied by structured medical examinations and by recording adverse experiences in mothers and children. Results There were no significant differences between the desogestrel and IUCD groups in composition and quantity of breast milk nor in growth and development of the children followed up to the age of 2.5 years. In the desogestrel group a slightly higher incidence of mild adverse experiences of a hormonal nature was reported among both mothers and infants. Of the children 82% were followed until 1.5 years of age and 50% until 2.5 years. Conclusion The use of desogestrel 75μg/day did not change the amount and composition of breast milk nor did it affect growth and development of the breastfed children. It appears to be a safe and effective contraceptive method for lactating women

Oral Contraceptives, Hormone Replacement Therapy and Thrombosis

Oral contraceptives and hormone replacement therapy are used by hundreds of millions of women worldwide. Since the early 1960s it is known that female hormones increase the risk of venous thrombosis, myocardial infarction and stroke. This risk is still present with current low-dose oral contraceptives and, even though in absolute terms the risk is small, oral contraceptives form the major cause of thrombotic disease in young women. The risk is higher during the first year of use (up to I per 1000 per year), with the use of desogestrel- or gestodene-containing oral contraceptives ("third generation progestogens") and among women with a prothrombotic predispositon. Hormone replacement therapy increases the risk of venous thrombosis, while results of randomised trials so far do not substantiate the expectation of a beneficial effect on the risk of arterial cardiovascular disease. First results are emerging that specific subgroups of women, with prothrombotic or other abnormalities, may be at risk, especially during the first years of use of hormone substitution.