Switching from cetrorelix to dydrogesterone in an IVF cycle - a new strategy for unexpected freeze-all cycles.

Preventing a luteinizing hormone (LH) surge is a major concern in controlled ovarian stimulation (COS). Several strategies have been developed over the years, including protocols with Gonadotrophin Releasing Hormone agonists and antagonists. More recently Progestin Primmed Ovarian Stimulation (PPOS) has shown to be equally effective in pituitary suppression, with comparable clinical and laboratorial outcomes. This is the case of a 34 year old female, with a previous diagnosis of primary infertility due to tubal factor and high ovarian reserve markers. The initial plan was to perform IVF/ICSI. followed by fresh blastocyst transfer. The chosen COS strategy was to use Alfacorifolitropin 150mg (Elonva®) and Cetrorelix acetate 0,25mg (Cetrotide®) in a flexible pituitary suppression protocol. However, because of elevated risk for Ovarian Hyper-stimulation Syndrome (OHSS) detected during ultrasound and hormonal monitoring, in order to diminish financial burden and to have a more patient friendly protocol, we switched cetrorelix acetate to oral dydrogesterone. COS was successful and resulted in 24 retrieved oocytes (16 metaphase 2 oocytes) without any premature LH peak. No OHSS symptoms occurred. Our main goal with this case report is to reinforce the feasibility and efficacy of this innovative approach, especially in patients aiming for a fresh embryo transfer, who present alert sings of OHSS during the stimulation. Developing friendlier and cheaper protocols in assisted reproduction makes the treatment more accessible and affordable.

Método de Ovulação Billings: entre eficácia e desconhecimento / Billings Ovulation Method: between efficacy and lack of knowledge / Método de Ovulación Billings: entre la eficacia y el desconocimiento

Resumo Apesar dos grandes investimentos, os métodos artificiais de planejamento familiar ainda apresentam limitações. Desde a década de 1950, cientistas trabalham para desenvolver um método natural confiável. Este artigo revisa a literatura sobre o Método de Ovulação Billings, apontando sua lógica, sua eficácia, seus benefícios, seus desafios e suas regras. Trata-se de método natural, embasado em mais de cinquenta anos de pesquisas. Sua chave de leitura é o muco cervical, confiável indicador da fertilidade, e sua eficácia está entre 97% e 99%, comparável aos métodos mais eficazes. O método também é indicado para todo tipo de ciclo, pois não se baseia em cálculos, e sim na observação do muco. Conclui-se que no Brasil é preciso fortalecer programas que ofereçam educação sexual mais global à população, capacitando ainda profissionais da saúde a respeito dos métodos naturais de planejamento familiar.

Abstract Despite large investments, artificial family planning methods still have limitations. Since the 1950s, scientists have worked to develop a reliable natural method. This article reviews the literature on the Billings Ovulation Method, pointing out its logic, efficacy, benefits, challenges, and rules. It is a natural method, based on more than fifty years of research. Its reading key is the cervical mucus, a reliable indicator of fertility, and its efficacy is between 97 and 99%, comparable to most effective methods. Billings is also suitable for all types of cycles, as it is not based on calculations, but on the observation of the mucus. In conclusion, Brazil needs to strengthen programs that offer more global sexual education to the population, also training health professionals on natural family planning methods.

Resumen A pesar de las grandes inversiones, los métodos artificiales de planificación familiar todavía tienen limitaciones. Desde la década de 1950, los científicos vienen trabajando para desarrollar un método natural confiable. Este artículo revisa la literatura sobre el Método de Ovulación Billings, presentando su lógica, efectividad, beneficios, desafíos y reglas. Se trata de un método natural, basado en más de cincuenta años de investigación. Su clave es el moco cervical, un indicador confiable de fertilidad, y su efectividad está entre el 97% y el 99%, comparable a los métodos más efectivos. El Método de Ovulación Billings también es adecuado para todo tipo de ciclos, ya que no se fundamenta en cálculos, sino en la observación de mocos. Se concluye que en Brasil es necesario fortalecer programas que ofrezcan una educación sexual más global a la población, además de capacitar a los profesionales de la salud sobre métodos naturales de planificación familiar.

Ovulatory status of overweight women without Polycystic Ovary Syndrome.

OBJECTIVE: Obesity is one of the extra hypothalamic-pituitary-ovarian axis factors that can influence ovulation. The isolated impact of obesity on ovulation without other comorbidities needs to be further studied. Our goal is to evaluate the association between the anovulation in the ultrasonographic monitoring of the ovulation cycle and the body mass increase of infertile patients without polycystic ovaries of a university service. METHODS: Case-control study performed at the Human Reproduction Laboratory of the University Hospital. We evaluated 1,356 ultrasound monitoring reports of ovulation between January 2011 and December 2015. We named case those patients who ovulated on the monitored cycle. After applying the exclusion criteria, we consolidated a total of 110 cases and 118 controls. The exposure variables were normal BMI or patients classified with a BMI above normal. Data analysis was performed using SPSS 22.0. Differences in proportions were assessed by X2 test Pearson, Fisher and Wilcoxon test. The value of p<0.05 was considered statistically significant. RESULTS: The groups were comparable in age, age at menarche, number of pregnancies, deliveries, cesarean sections and abortions, number of antral follicles, FSH, prolactin and TSH values. Among the anovulatory patients, 57 (51.82%) were overweight, while among ovulatory patients, 44 (37.29%) were in this same BMI category. The odds ratio was 1.8655, with a significant p value (p<0.05). CONCLUSION: There was an association between anovulation and increase in the Body Mass Index, with an increased risk of anovulation in patients with BMI above normal.

Towards the Clinical Evaluation of the Luteal Phase in Fertile Women: A Preliminary Study of Normative Urinary Hormone Profiles.

Objective: To describe and evaluate urinary hormone profiles in the luteal phase. Setting and Patients: Twenty-five healthy fertile women, with regular ovulatory pattern cycles as assessed by temperature and cervical mucus, at a university based center. Methods: Daily urinary hormonal assessment of luteinizing hormone, estrone glucuronide, and pregnanediol glucuronide. This was done during 3 or more cycles, with 78 completed cycles. Samples were analyzed by both crude levels and levels adjusted for the hormone excretion rate. Correlation between measured parameters (LH surge, vulvar mucus) was assessed with regard to their ability to detect presumed ovulation. Results: An upper, middle, and lower tercile range for the main urinary reproductive hormones was determined and a classification system of zones proposed, considering profiles over or under the 10th percentile. Adjustment for the urine excretion rate proved useful for interpreting individual samples; this was less necessary with multiple samples over time where trends could be determined. This serial evaluation, in at least two cycles, lowered the possibility of finding an isolated luteal phase defect and helped identify the recurrence of such. Vulvar mucus findings performed well in determining the timing of ovulation. Despite the proven fertility of the study population, lower luteal phase hormones were detected in both an isolated and, in some situations, recurrent manner. Conclusion: A feasible method is proposed to accurately, thoroughly and reproducibly study the luteal phase in order to evaluate and treat identified abnormalities in a properly timed, restorative manner. This preliminary study provides the basis for future research, correlating urinary hormones with clinical findings, particularly those of luteal phase defects.

Patients' auto report of regularity of their menstrual cycles. Medical history is very reliable to predict ovulation. A cross-sectional study.

OBJECTIVE: Infertility of ovulatory cause can account for a quarter of infertility etiologies and one of the questions in the patients' clinical history is about their self-perception of the regularity of their menstrual cycles. The aim of this study was to assess whether the information on menstrual regularity is consistent with the assessment of the presence or absence of ovulation. METHODS: Cross-sectional study. The inclusion criteria were: patients with infertility for at least one year, complete examination and ovulation monitoring, aged between 18 and 38 years completed. The patients were divided into two paired groups: those who reported regular menstrual cycles and those who reported irregular cycles. In the ultrasonographic monitoring of ovulation we separated those who ovulated from those who did not ovulate, and applied the Fischer's test. RESULTS: Among the 199 patients who reported having regular menstrual cycles, 113 had proven ovulation upon ultrasound monitoring and 86 patients did not ovulate. Among the 29 patients who reported irregular cycles, 24 did not ovulated at the cycle monitoring. The Fisher's exact test was applied and the p-value found was significant. CONCLUSION: The story of the patient in the clinical interview about the presence of regular or irregular menstruation correlates with the presence or absence of ovulation, it should be taken into consideration in the reasoning regarding the infertility etiology. This report would be important to guide the patient's ovulatory regularity diagnosis.

Infertility in bitches and queens: recent advances / Infertilidade na cadela e gata: atualidades

In comparison to the last 10 or 20 years, veterinarians are now frequently requested to solve fertility problems in the dog and cat, mainly due to the increased popularity of purebred dogs as well as for sentimental or financial reasons. Infertility in dogs and cats can be due to wrong breeding management, uterine disease, ovarian disease, failure of the male to achieve a complete mount, or poor semen quality. From a practical standpoint, fertility means achieving conception, then establishing a pregnancy through implantation and carrying the pregnancy to term.(AU)

Comparando-se os últimos 10 - 20 anos, os veterinários têm sido freqüentemente procurados para resolver problemas de fertilidade na cadela e gata, principalmente devido ao aumento da popularidade das raças puras, bem como por questões sentimentais ou ainda por razões financeiras. Do ponto de vista prático, fertilidade significa atingir a concepção, estabelecer uma gestação e levar a mesma a termo. A infertilidade em cadelas e gatas pode estar relacionada com erros no manejo da cobertura, doenças uterinas e/ou ovarianas, falha do macho em realizar a monta completa ou devida á qualidade insatisfatória do sêmen.(AU)

Infertility in bitches and queens: recent advances / Infertilidade na cadela e gata: atualidades

In comparison to the last 10 or 20 years, veterinarians are now frequently requested to solve fertility problems in the dog and cat, mainly due to the increased popularity of purebred dogs as well as for sentimental or financial reasons. Infertility in dogs and cats can be due to wrong breeding management, uterine disease, ovarian disease, failure of the male to achieve a complete mount, or poor semen quality. From a practical standpoint, fertility means achieving conception, then establishing a pregnancy through implantation and carrying the pregnancy to term.

Comparando-se os últimos 10 - 20 anos, os veterinários têm sido freqüentemente procurados para resolver problemas de fertilidade na cadela e gata, principalmente devido ao aumento da popularidade das raças puras, bem como por questões sentimentais ou ainda por razões financeiras. Do ponto de vista prático, fertilidade significa atingir a concepção, estabelecer uma gestação e levar a mesma a termo. A infertilidade em cadelas e gatas pode estar relacionada com erros no manejo da cobertura, doenças uterinas e/ou ovarianas, falha do macho em realizar a monta completa ou devida á qualidade insatisfatória do sêmen.

Natural family planning: suitability of the CUE method for defining the time of ovulation.

The purpose of this study was to compare the CUE method for family planning with the Ovulation Detection Method for defining the fertile phase of the menstrual cycle. We evaluated 42 cycles from 10 women in Monterrey, Mexico, who were monitored by basal body temperatures, urinary LH, pelvic ultrasound, and the CUE monitor. The fertile phase of the cycle was adequately defined in all cycles using the CUE method, and in 35 cycles (83.3%) by the Ovulation Method. Using our protocol, the period of recommended abstinence with the CUE method is 9 days and with the Ovulation Method 11 days. The CUE method accurately defines the fertile phase of the menstrual cycle, thus improving the predictability of ovulation for women who use natural methods of birth control.

PIP: To evaluate the potential utility of the CUE method in natural family planning (NFP), this method was compared with a standard NFP technique, the Ovulation Method, in 39 cycles of 10 women from Monterrey, Mexico. All women had more than 2 years' experience with the Ovulation Method. In the CUE method, ovulation prediction is based on a peak in salivary electrical resistance and its confirmation by a rise in vaginal resistance as monitored by a hand-held electronic instrument attached to a specially designed sensor. The CUE method defined the fertile period of all 39 cycles adequately, while the Ovulation Method resulted in incorrect definition of the fertile phase in 4 (10%) of 39 cycles. The salivary peak predicted ovulation an average of 8 days in advance of its occurrence and the increase in vaginal readings in the periovulatory period was seen within 1 day of follicle collapse in all subjects. The duration of abstinence required by the CUE method would have averaged 9.0 +or- 1.5 days (range, 6-13 days). In contrast, the average duration of abstinence associated with the Ovulation Method was 11.0 +or- 2.9 days (range, 6-16 days). 82% of cycles monitored by the CUE method compared with only 53% of those monitored by the Ovulation Method would have required a period of abstinence of 10 days or less. The simplicity and objectivity of the CUE method, combined with its requirement for fewer days of abstinence, offer the potential for improving NFP compliance and continuation.

Breast-feeding and the return to ovulation in Durango, Mexico.

Twenty-nine breast-feeding mothers and 10 non-breast-feeding postpartum comparison mothers from a rural area of Mexico were followed longitudinally until ovulation resumed. A simple set of guidelines is described involving three obvious milestones for the breast-feeding mother to safely use the natural contraceptive benefit of breast-feeding. Those milestones are: the first vaginal bleeding episode, the initiation of supplementation, and the child's monthly birthday. In the absence of bleeding and supplementation, 100% of breast-feeding mothers remained anovular for 3 months postpartum, 96% for 4 months, 96% for 5 months, and 96% for 6 months. This suggests that, if a mother understands these three conditions, she can use breast-feeding alone as effectively as modern family planning methods for the prevention of pregnancy.

A prospective multicentre trial of the ovulation method of natural family planning. II. The effectiveness phase.

A five-country prospective study was undertaken to determine the effectiveness of the ovulation method of natural family planning. After successful completion of a teaching phase of three cycles, 725 subjects entered a 13-cycle effectiveness phase and contributed 7514 cycles of observation. The overall cumulative net probability of discontinuation for the effectiveness study after 13 cycles was 35.6%, 19.6% due to pregnancy. Pregnancy rates per 100 woman-years calculated using the modified Pearl index were as follows: conscious departure from the rules of the method, 15.4; inaccurate application of instructions, 3.5; method failure, 2.8; inadequate teaching, 0.4; and uncertain, 0.5.

PIP: A 5 country prospective study was undertaken to determine the effectiveness of the ovulation method of natural family planning. 869 subjects of proven fertility from 5 centers (Auckland, Bangalore, Dublin, Manila, and San Miguel) entered the teaching phase of 3-6 cycles; 765 (88%) completed the phase. 725 subjects entered a 13-cycle effectiveness phase and contributed 7514 cycles of observation. The overall cumulative net probability of discontinuation for the effectiveness study after 13 cycles was 35.6%, 19.6% due to pregnancy. Pregnancy rates per 100 woman-years calculated using the modified Pearl index were as follows: conscious departure from the rules of the method, 15.4; inaccurate application of instructions, 3.5; method failure, 2.8; inadequate teaching, 0.4; and uncertain, 0.5. Cycle characteristics included: 1) average duration of the fertile period of 9.6 days, 2) mean of 13.5 days occurred from the mucus peak to the end of the cycle, 3) a mean of 15.4 days of abstinence was required, and 4) a mean of 13.1 days of intercourse was permitted. Almost all women were able to identify the fertile period by observing their cervical mucus but pregnancy rates ranged from 27.9 in Australia and 26.9 in Dublin to 12.8 in Manila. Continuation was relatively high ranging from 52% in Auckland to 74% in Bangalore.

A prospective multicentre trial of the ovulation method of natural family planning. I. The teaching phase.

The percentage of 869 women in five countries capable of being taught to recognize the periovulatory cervical mucus symptom of the fertile period was determined in a prospective multicentre trial of the ovulation method of natural family planning. The women were ovulating, of proven fertility, represented a spectrum of cultures and socioeconomic levels, and ranged from illiteracy to having postgraduate education. In the first of three standard teaching cycles, 93% recorded on interpretable ovulatory mucus pattern. Eighty-eight per cent of subjects successfully completed the teaching phase; 7% discontinued for reasons other than pregnancy, including 1.3% who failed to learn the method. Forty-five subjects (5%) became pregnant during the average 3.1-cycle teaching phase. The average number of days of abstinence required by the rules of the method was 17 in the third teaching cycle (58.2% of the average cycle length). To what extent the findings of this study can be extended to other couples remains to be demonstrated.

PIP: A prospective multicenter study was conducted in 5 cities (Auckland, Bangalore, Dublin, Manilla, and San Miguel) to assess the teaching phase of a program on the ovulation method (OM) of natural family planning. 869 ovulating women of proven fertility representing a wide range of cultural, educational, and socioeconomic characteristics (83% Catholic) were taught to recognize the cervical mucus symptom of the fertile period and were then tested on the effectiveness of their learning. 52% of the subjects did not wish to have any more children. 93% were able to understand the method after 1 cycle and 97% after 3 cycles. In the 3rd cycle, the mean number of days of abstinence required was 17. 75.1% of the subjects entered the 2nd phase of the trial after the 1st 3 training cycles and an additional 8.3% after an extended period of up to 3 more cycles. 45 (5.2%) became pregnant during teaching and 99 (11.4%) withdrew from the study. 2, possibly 3, subjects became pregnant while following OM rules. 32 pregnancies occurred when couples had intercourse during the fertile period and 11 more resulted from inaccurate application of the instructions. Subjects who required teaching beyond the 1st 3 teaching cycles reported both pregnancy and discontinuation rates more than 4 times higher than women who did not require additional teaching.

[Family planning: "Billing's" ovulation method]. / Planejamento familiar: método da ovulação "Billings".

PIP: The Billings method of contraception, or cervical mucus method, is being introduced, apparently with great success, in Brazil. This method was studied and perfected by the Drs. Billings during the 1950s in Australia; the book explaining how the method works, was published in 1964, and it was soon followed by many other studies. The method is based on the observation of the cyclic changes of cervical mucus. During the first phase of the cycle, or proliferative phase, the increased estrogen secretion produces abundant, wet, elastic mucus, of a quality very conducive to sperm transport; the peak of the mucus symptom coincides with ovulation or precedes it about 1 day. Couples must refrain from intercouse during this period. The second phase of the cycle, or secretory phase, is characterized by increased progesterone secretion which inhibits production of cervical mucus; these are the infertile days of the cycle; mucus will be scant, and dry. This method, which implies periodic sexual abstinence, can by very advantageously used to prevent or to obtain pregnancy. A couple wanting to use this method will have to carefully chart the daily appearance in quantity and quality of cervical mucus, and will have to be instructed on how to do so. The failure rate of the method goes from 0.48 to 2.9/100 women year. The method is totally safe and it promotes marital communication and understanding.^ieng

[Diagnostic of the estimated time of ovulation by ultrasounds (author's transl)]. / Daignosyico do dia provavel da ovulacao pela ultra-sonografia.

PIP: Recent experiments have demonstrated that it is possible to detect ovulation by ultrasounds; the examination, which is totally safe and lasts about 5 minutes, should be done during the early follicular phase and daily during the preovulatory period. The diameter of the follicle is usually 2.0-2.5 cm. between day 1 and day 0, which registers the maximum LH (luteinizing hormone) peak, i.e. is the estimated time of ovulation. After day 0 one can either observe the disappearance of the follocular image, or the appearance of the corpus luteum, which can be identified during 24-48 hours.^ieng

[Determination of urinary pregnanediol as an ovulation parameter]. / Medición de pregnandiol urinario como parametro de ovulacion

PIP: For women who are not pregnant, the excretion of pregnanediol can be measured to determine if ovulation has occurred. During the preovulatory stage excretion is low, but 3 or 4 days after ovulation it increases greatly. In this study, Klopper's procedure for the study of ovarian function was followed with some modifications by Goldzieher and Nakamura to obtain results fairly quickly. The standardization of the method was arrived at by determining the absorption spectrum and the spectometry of pregnanediol diacetate. The method was evaluated by studying its specification, accuracy, precision, and sensitivity. The menstrual cycles of 6 normal women were studied. In all cases, in the postovulatory phase the excretion of pregnanediol was higher than 1.3 mg in 24 hours of urine, indicating an increase in progesterrone excretion produced by the corpus luteum. The advantages of this method for determination of ovualtion are that no instruments are required, the sensitivity of the method is high, and it can be repeated often without bothering the patient, especially importnt for women with irregular cycles.^ieng

[Participation of 17 alpha-hydroxyprogesterone in the mechanism of ovulation]. / Participación de la 17 alfa-hidroxiprogesterona en el mecanismo de la ovulación.

PIP: Progesterone (P) and 17 alpha-hydroxyprogesterone (17 OH-P) were analyzed daily during the menstrual cycle in women with both ovulatory and anovulatory cycles, without any other endocrine alteration. The plasma levels of 17 OH-P in 65 samples obtained during the follicular phase of the ovulatory cycles were 1.057 ng/ml, consistently higher than the P levels, which were .492 ng/ml, with a 17 OH-P/P ratio of 2.16. On the other hand, the plasma levels of 17 OH-P obtained during the same phase of the anovulatory cycles were .288 ng/ml. The difference between ovulatory and anovulatory cycles was statistically significant (p less than .001). The P levels were .156 ng/ml and the 17 OH-P/P ratio was 2.76. In the 2nd part of the ovulatory cycles, the 17 OH-P/P ratio was .46, and in the same part of the anovulatory cycles the ratio was 2.39. The total values of both steroids and the individual values of 17 OH-P differed between the 2 types of cycles (p less than .001). The findings show that 17 OH-P is an indicator of follicular development and that it could be used to predict the occurrence of ovulation.^ieng

[Study of the basal temperature, cervix mucus, vaginal cytology, spermatic penetration, and length of the menstrual cycle, in patients under clomiphene treatment]. / Estudio de la temperatura basal, moco cervical citología vaginal, penetración espermática y duración del ciclo menstrual, en las paientes en tratamiento con clomifeno.

PIP: 55 patients under clomiphene treatment were studied during 149 cycles. In addition to the usual tests and controls, the authors made a basal temperature curve, took samples of cervical mucus and performed vaginal cytology tests, and calculated the average duration of the cycle. The cycle study based on the Sims Huhner test was also performed on 13 patients. Changes in the results of the tests were found to be related to the dosage and, above all, to the date on which treatment is started. Knowing the changes that occur in the cervical mucus and basal temperature, these 2 tests helped in detecting ovulation. Postcoital cervical sperm penetration improved 1 week after taking the last tablet. The duration of the menstrual cycle increased while taking the drug, and this prolongation of the cycle increased as the drug was administered at a later stage. With respect to vaginal cytology, it is necessary to know the changes that occur in order to interpret the findings correctly; vaginal cytology studies are unreliable in determining the occurrence and especially the probable date of ovulation.^ieng

[Mechanism of action of prolonged-action injectable contraceptives]. / Mecanismo de accion de los contraceptivos inyectables de deposito.

PIP: Several parameters were studied to clarify the mechanisms of action of 2 prolonged-action injectable contraceptives: 17alpha-19-hydroxynorprogesterone caproate (with a contraceptive effectiveness of at least 8 weeks) and 19-norethindrone enanthate (effectiveness over 12 weeks). The generally accepted theory of ovulation inhibition was unconvincing. In 14 ovarian biopsies of patients under treatment, taken in the 2nd phase of the cycle, ovulation was evidenced in 11 cases by the presence of corpora lutea. 245 endometrial biopsies showed that the exogenous gestagen effect lasts only 3 weeks; after such period, most endometria could be correlated with the day of the cycle on which they were taken; 2/3 of them suggested biphasic cycles. An evaluation of 240 colpocytograms also confirmed endogenous cyclic activity. In order to explain the prolonged contraceptive effectiveness of the drugs, the cervical mucus was thoroughly studied in 380 cases. A definite, uniform, and constant effect of the progestogen on the mucus was demonstrated, in contrast to the cyclic changes in the other parameters; such effect begins to decline simultaneously with the loss of contraceptive protection. It is suggested that the effectiveness of the 2 drugs is due to changes in the cervical mucus, which affect sperm penetration.^ieng