Steroidogenesis in vitro of human granulosa-luteal cells pretreated in vivo with two gonadotropin releasing hormone analogs employing different protocols

We have previously observed impaired progesterone accumulation in vitro in response to human chorionic gonadotropin (hCG) by cells pretreated in vivo with a gonadotropin releasing hormone analog (GnRH-a). The present study was conducted in order to evaluate different protocols for GnRH-a in in vitro fertilization (IVF), employing two different available analogs. Granulosaluteal cells were collected at ovum pick-up and stimulated with hCG. Buserelin (Bus) was employed as long (Bus-L) and short (Bus-S) protocol, and Leuprolide (Leu) was also used as long (Leu-L) and short (Leu-S) protocol. Progesterone accumulation in vitro was compared with cells treated with domiphene citrate (CC) and gonadotropins. Maximal progesterone production was observed on culture day 6 using Bus-L in comparison to day 4 when domiphene citrate was employed. While Leu-S showed a similar pattern of progesterone accumulation to domiphene citrate, Leu-L and Bus-S had an intermediate pattern. The response to hCG was maximal on day 4 for the domiphene citrate- and Leu-S-treated cells, while the rest of the protocols had a peak on day 6. In addition, hCG consistently stimulated progesterone production in all protocols except in Bus-L. These results confirm an altered progesterone accumulation in vitro when GnRH-a are used. The effect seems to be more evident in long protocols, especially when buserelin is used, suggesting a higher accumulation of the analog in follicular fluid.     

Patterns of Progression and Nonprogression Through In Vitro Fertilization Treatment

Purpose: Increasing numbers of couples are consulting for infertility and, after some years of investigation and treatment, will become enrolled in in vitro fertilization (IVF) programs. The media have focused on successful outcomes or difficulties in accessing services because of health authority funding guidelines. Couples are often assumed to be highly motivated because of their long prior involvement in treatment. However, little is known about uptake of and continuation through IVF treatment programs. Methods: One hundred forty-four couples were followed through the process of IVF in a service that allows three cycles of treatment, with a minimum gap of 3 months between treatment cycles. Patterns of engagement in and delay and withdrawal from treatment were examined. Results: One in five couples withdrew from the program before completion of the available number of treatment cycles. A further one in three significantly delayed their involvement in treatment cycles. Mean deviations of the time between attempts increased as the number of treatment cycles progressed. A proportion of couples did not complete a single treatment cycle. Conclusions: The dramatic proportions of patients withdrawing from or very significantly delaying subsequent involvement are indicative of the often unacknowledged difficulties associated with IVF treatment. Implications for care are discussed.     

A short length of gonadotropin hyperstimulation is sufficient to achieve an optimal IVF outcome in advance-aged women

ObjectiveTo analyze the duration of gonadotropin hyperstimulation's impacts on oocyte quality and clinical outcomes in aged in vitro fertilization (IVF) patients.Materials and methodsThis retrospective study was carried out using IVF records of the Chang Gung Memorial Hospital IVF center from January 2017 to December 2019. A total of 308 IVF cycles with patients aged 40–44 years were included. Clinical characteristics of patients who received a short controlled ovarian hyperstimulation (COH) (i.e., 6–7 days; s-COH group) or a long COH treatment (i.e., 9–10 days; l-COH group) were compared. In addition, analysis was conducted using data within two age subgroups: 40–42 years and 42–44 years subgroups.ResultsThe s-COH group received significantly lower total doses of gonadotropin and had smaller leading follicles at the time of ovulation trigger when compared to the l-COH group. The s-COH group also produced a significantly lower number of oocytes, mature metaphase II (MII) oocytes, and 2 PN zygotes compared to the l-COH group. However, there was no significant difference in the number of transferable and good-quality embryos between the two treatment groups. Likewise, the pregnancy rate and live birth rate were comparable in the s-COH and l-COH groups. Similar results were obtained when the analysis was limited to select age subgroups (i.e., 40–42 and 42–44 years subgroups).ConclusionWhile a long COH generates more oocytes per cycle, a 6–7 days COH treatment, which is at the lower end of the recommended window of stimulation, could achieve a pregnancy outcome comparable to that applied 9–10 days of COH in aged patients.     

Prevalence of body mass index and body weight cut-off points for in vitro fertilization treatment at U.S. clinics and current clinic weight loss strategy recommendations

The goal of this study was to determine how many clinics providing in vitro fertilization (IVF) in the United States require a body mass index (BMI) or body weight cut-off point to determine treatment eligibility. US clinics listed as members on the Society of Assisted Reproduction website in late 2013 were contacted by phone between January and March 2014. Clinic personnel were asked if a BMI or body weight cut-off points was used to determine IVF treatment eligibility and what strategies they recommended for their patients to achieve a healthy body weight. Of the 379 clinics contacted, 347 responded (92% response rate) and 35% (n = 120) reported using a BMI or body weight cut-off points to determine eligibility for IVF treatment. Mean BMI (± SD) cut-off points was 38.4 ± 5.2 kg/m² and mean body weight (± SD) cut-off points was 130.2 ± 14.8 kg. Of the clinics using a set cut-off points, half (46%) provided no weight loss recommendations for patients. A sizable portion of US IVF clinics report a required or preferred BMI or body weight cut-off points for treatment. Despite this, most clinics did not provide a recommended program or approach for weight loss with very few clinics reporting an in-house program.     

Intrafollicular and serum levels of leptin during in vitro fertilization cycles: comparison between the effects of recombinant follicle-stimulating hormones and human menopausal gonadotrophin

Objectives.?To compare the effect of recombinant follicle-stimulating hormones (r-FSH) and human menopausal gonadotrophin (hMG) on leptin levels in serum and follicular fluid (FF) during in vitro fertilization IVF/ET treatment, and to investigate whether leptin levels in the follicular fluid and/or serum are correlated with IVF success.

Methods.?Sixty-three patients undergoing IVF cycle were subdivided into two groups. r-FSH was used to for controlled ovarian hyperstimulation in 29 patients (Group A) while, hMG was used in 34 patients (Group B). Our main outcomes were serum and FF leptin on the day of oocyte collection.

Result(s).?The two groups were comparable in age, body mass index (BMI), indications for IVF/ET, E2 level on human chorionic gonadotrophin day, number of retrieved oocytes, fertilization rate, number of transferred embryos and pregnancy rate. Serum and FF leptin levels were similar between the two study groups. Additionally, no correlation was found between levels of leptin in either serum or FF and cycle results such as: number of retrieved oocytes, fertilization rate and pregnancy rate.

Conclusions.?r-FSH and hMG have been found to have comparable effects on leptin levels in the serum and the FF of patients undergoing IVF/ET. Additionally, leptin levels in both serum and FF on day of retrieval have no correlation to IVF/ET outcome.     

Ovarian Endometriomas Do Not Adversely Affect Pregnancy Success Following Treatment With In Vitro Fertilization

Purpose: Ovarian endometriomas have an uncertain impact on outcome following in vitro fertilization (IVF). Some authors describe a poor response to ovulation induction, and others observe decreased pregnancy success rates. Conversely, IVF outcomes similar to those of patients undergoing IVF for tubal-factor infertility have also been reported. To determine the impact of ovarian endometriomas on pregnancy success in our IVF program, we identified patients with endometriosis and compared outcomes that were stratified by the presence or absence of an endometrioma at the time of follicular aspiration. Methods: One hundred eight patients with a diagnosis of endometriosis treated with IVF were identified, retrospectively. In this group, 24 patients completed 29 cycles in which an ovarian endometrioma was aspirated at the time of oocyte retrieval, and 84 patients without endometriomas completed 147 cycles. The cycles from these two groups were compared for differences in peak estradiol, number of mature follicles, number of oocytes, number of embryos transferred, and clinical pregnancies. Results: There were no significant differences between the two groups with respect to peak estradiol, mature follicles, number of oocytes, number of embryos transferred, or clinical pregnancies. Conclusions: From this retrospective observational analysis it appears that aspiration of an endometrioma at the time of oocyte retrieval has no adverse effect on outcome. This information may prove helpful when faced with the decision to cancel an IVF treatment cycle in patients with this uncommon complication.     

Low grade inflammation, as evidenced by basal high sensitivity CRP, is not correlated to outcome measures in IVF

Purpose  To assess the relationship between low-grade inflammation, measured as basal high sensitivity (hs)-CRP, and IVF outcome. Methods  We recruited a total of 220 women undergoing infertility work up prior to IVF. Patients were selected for a BMI < 30 kg/m² with an upper age limit of 40 years. Serum hs-CRP levels were measured on day 3 of a spontaneous menstrual cycle preceding ovarian stimulation. A sensitive two-site ELISA was used for analysis. Dose of gonadotrophins required, follicles days 8 and 10, number of oocytes collected, number of oocytes fertilised and pregnancy outcome were recorded. Results  Median hs-CRP was 1.08 mg/L (0.43–3.00 mg/L). The hs-CRP was significantly related to BMI (r = 0.386, P < .001) but not to age and smoking habit. There were no significant relationships between basal hs-CRP and any of the measured IVF outcomes. Conclusions  These findings demonstrate that serum hs-CRP concentration is not a predictive marker of cycle or pregnancy outcome in women undergoing IVF treatment. Capsule   Basal low-grade inflammation does not predict IVF success as shown by the lack of correlation between day 3 hs-CRP and IVF outcome measures.     

Dexamethasone Supplementation to Gonadotropin Stimulation for In Vitro Fertilization in Polycystic Ovarian Disease

Purpose: This study was conducted to determine whether glucocorticoid supplementation for patients with polycystic ovarian disease during ovulation induction with gonadotropins for in vitro fertilization (IVF) therapy is beneficial. Methods: Seventy-one cycles of patients undergoing first attempts at IVF, with classical polycystic ovarian disease and hyperandrogenemia, who enrolled in the IVF–embryo transfer program, were evaluated retrospectively. In 20 cycles (20 patients) glucocorticoid supplementation was noted and compared to 51 cycles (51 patients) without glucocorticoid as adrenal androgen suppression. Ovaries were stimulated by gonadotropin releasing hormone agonist, human menopausal gonadotropin, and dexamethasone. Ovarian responsiveness and IVF–embryo transfer outcome were analyzed and included the number of follicles >17 mm in diameter, serum estradiol concentration on the day of human chorionic gonadotropin administration, number of human chorionic gonadotropin ampoules administered, number of oocytes retrieved, percentage of oocytes fertilized, number of embryos transferred, implantation rate, and number of clinical pregnancies and their outcome. Results: The results showed that the pregnancy rate in patients who received glucocorticoid was 22.1%, compared to 26% in the controls (statistically insignificant). The IVF cycle variables studied revealed no statistically significant differences. Conclusions: Our observations did not support the notion that adrenal androgen suppression by glucocorticoid, or as an adjuvant therapy, is beneficial to patients with polycystic ovarian disease who enrolled in an IVF–embryo transfer program.     

The effect of performing hysteroscopy prior to the first in vitro fertilization (IVF) cycle on live birth rate

Abstract

In this retrospective cohort study, a total of 707 couples underwent in vitro fertilization (IVF) at Hacettepe University Hospital between 01 January 2010 and 01 November 2014 with their chronologically first cycle were evaluated. Patients who have diagnostic hysteroscopy prior to first IVF cycle served as a study group (n?=?42) and patients without diagnostic hysteroscopy served as control group (n?=?282). In study group in all patients, diagnostic hysteroscopy was performed at the follicular phase of previous menstrual cycle, namely immediately before ovarian stimulation (OS) cycle. Demographic features, clinical characteristics and treatment outcomes were compared between the groups. The logistic regression analysis was performed in order to assess independent predictors of live birth rates (LBRs). There was no statistically significant difference between the groups for demographic features and OS cycle characteristics. Implantation rate (22.2% vs. 21.5%, p=.840), clinical pregnancy rate (33.3% vs. 28.7%, p=.541), and LBRs (23.8% vs. 18.5%, p=.420) were comparable. In logistic regression analysis, performing hysteroscopy prior to first IVF cycles per se without correcting anatomic abnormalities was not an independent predictor of LBRs (OR: 0.72, 95% CI: 0.310–1.68, p=.45). In conclusion, performing diagnostic hysteroscopy prior to first IVF treatment cycle without correcting any anatomic abnormalities did not improve LBRs.     

Assisted reproduction professionals' awareness and attitudes towards their own IVF cycles

Objective: Professionals involved in assisted reproductive technologies (ART) have in-depth awareness and knowledge of the risks of multiple pregnancies at the conclusion of in vitro fertilization (IVF) treatment. The aim of the study was to investigate ART professionals' attitudes towards the awareness of the risk of infertility, as well as the decision-making process in IVF issues.

Methods: Seventy ART professionals answered a questionnaire covering demographic data, infertility awareness and attitudes towards IVF.

Results: Approximately half (50.8%) of the participants thought that they were not at risk of infertility. However, if they received a diagnosis of infertility, none would accept childlessness and almost all would undergo IVF. In an IVF cycle, the number of high-quality embryos transferred would be around three, but if treatment was extended to a third cycle, a higher percentage of participants would elect to transfer four or more embryos. All participants would prefer to undergo IVF and accept the risk of multiple pregnancy than remaining childless. It was found that less than a third of ART professionals considered triplets to be an unacceptable complication of IVF.

Conclusions: Diagnosis of infertility affects all participants psychosocially, supporting the idea that the emotional aspects of wanting a biological child, and decision making about whether to undertake ART, outweigh the medical position regarding the risks and benefits of IVF.     

Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective,longitudinal, cohort study

Background.?Several factors can affect oocyte quality and therefore pregnancy outcome in assisted reproductive technology (ART) cycles. Recently, a number of studies have shown that the presence of several compounds in the follicular fluid positively correlates with oocyte quality and maturation (i.e., myo-inositol and melatonin).

Aim.?In the present study, we aim to evaluate the pregnancy outcomes after the administration of myo-inositol combined with melatonin in women who failed to conceive in previous in vitro fertilization (IVF) cycles due to poor oocyte quality.

Materials and methods.?Forty-six women were treated with 4 g/day myo-inositol and 3 mg/day melatonin (inofolic® and inofolic® Plus, Lo.Lipharma, Rome) for 3 months and then underwent a new IVF cycle.

Results.?After treatment, the number of mature oocytes, the fertilization rate, the number of both, total and top-quality embryos transferred were statistically higher compared to the previous IVF cycle, while there was no difference in the number of retrieved oocyte. After treatment, a total of 13 pregnancies occurred, 9 of them were confirmed echographically; four evolved in spontaneous abortion.

Conclusion.?The treatment with myo-inositol and melatonin improves ovarian stimulation protocols and pregnancy outcomes in infertile women with poor oocyte quality.     

Effects of women’s body mass index on in vitro fertilization success: a retrospective cohort study

Background: The purpose of this study is to evaluate the influence of body mass index (BMI) on the reproductive outcomes and clinical pregnancy rate after in vitro fertilization (IVF). Methods: This retrospective study was performed on 230 women undergoing first cycle of standard IVF between October 2008 and February 2010. The patients were classified into three groups according to their BMI (BMI < 20?kg/m², 20?kg/m² < BMI < 27.9?kg/m² and BMI > 28?kg/m²). Information regarding clinical pregnancy was compared within these three groups. Results: There was no significant relation between BMI and age, the number of aspirated follicles, transferred embryos, mature oocytes, days of taking human menopausal gonadotropin (HMG) ampules and the total number of HMG ampules among three BMI studied groups. Statistically significant difference was detected between BMI and endometrial thickness. Conclusions: BMI has no effect on IVF outcomes and clinical pregnancy after IVF. However, losing weight in obese women seems reasonable to prevent possible obstetrics complications.     

Effects of luteal estradiol pre-treatment on the outcome of IVF in poor ovarian responders

Background: In view of the discrepancies about the luteal estradiol treatment before stimulation protocols having some potential advantages compared with the standard protocols in poor ovarian responders undergoing IVF, a meta-analysis of the published data was performed to compare the efficacy of the luteal estradiol pre-treatment protocols in IVF poor response patients. Methods: We searched for all published articles. The searches yielded 32 articles, from which seven studies met the inclusion criteria. We performed this meta-analysis involving 450 IVF patients in luteal estradiol pre-treatment protocol group and 606 patients in standard protocol group. Results: The luteal estradiol protocol resulted in a significantly higher duration of stimulation compared with the standard protocol. In addition, the number of oocytes retrieved and mature oocytes retrieved were significantly higher in the luteal estradiol protocols than those in the standard protocols. The cycle cancellation rate (CCR) in the luteal estradiol protocols was lower than the standard protocols. Moreover, no significant difference was found in the clinical pregnancy rate (CPR). Conclusions: The addition of the estradiol in the luteal phase preceding IVF in poor responders improved IVF cycle outcomes, including increasing the number of oocytes retrieved and mature oocytes retrieved and decreasing the CCR.     

Human chorionic gonadotropin and intravaginal natural progesterone are equally effective for luteal phase support in IVF

This prospective randomized study compared human chorionic gonadotropin (hCG) and micronized transvaginal progesterone for luteal support in 310 in vitro fertilization (IVF) patients treated with leuprolide acetate and gonadotropins in a long protocol, and showing normal ovarian response. Both treatment groups were homogeneous for age, BMI, stimulation treatment and ovarian response. Pregnancy rates per embryo transfer were not significantly different (33.1% for the hCG group versus 38.7% for the progesterone group). For IVF patients with a normal response to stimulation under pituitary supression, the use of hCG or progesterone for luteal support does not seem to have any effect on pregnancy rate. The choice of luteal treatment must balance medical hazard and patient convenience, as both therapeutic regimens seem equally effective.     

Should high BMI be a reason for IVF treatment denial?

Our aim was to examine the influence of BMI on the live-birth rate following IVF/ICSI and evaluate its specific contribution among other factors thus enabling accurate reproductive policy development. All patients that underwent IVF/ICSI at our center during January 2012–July 2015 were included in this retrospective study. A total of 1654 ICSI cycles were divided into four groups according to the patient’s BMI (kg/m²): group I (normal weight): <25 (943 cycles); group II (overweight): 25–30 (403 cycles); group III (obese): 30–35 (212 cycles); group IV (morbid obesity): >35 (96 cycles). Comparing the four groups of BMI, mean age and number of previous ART cycles was significantly lower in group I compared to groups II, III and IV. Length of treatment was significantly shorter in group I compared to groups II, III and IV. Ovarian response to COH was comparable in terms of mean estradiol and progesterone levels on the day of hCG administration mean number of oocytes retrieved, fertilized and number of embryos transferred. Endometrial thickness was significantly lower in group IV. Outcome measures, such as implantation rate, clinical pregnancy rate (CPR) per cycle and per ET, as well as live-birth rates did not differ significantly between the groups, although in group IV LBR per cycle and per ET was lower. Multivariate logistic regression stepwise analysis found a significant correlation between age and BMI but did not find correlation between BMI and clinical pregnancy (p?=?0.436) or LB (p?=?0.206). The results of our relatively large retrospective study did not demonstrate a significant impact of BMI on the ART cycle outcome. Therefore, BMI should not be a basis for IVF treatment denial.     

Prospective patient and physician preferences for stimulation or no stimulation in IVF

Objective: The aim is to explore the preferences of female patients and physicians for IVF in three natural cycles compared to one stimulated cycle and to investigate which factors predict these preferences.

Study Design: A questionnaire about IVF preference was administered initially to 105 patients between 36 and 42 years, who were on the waiting list for their first or second IVF attempt. In addition a questionnaire was sent to 56 physicians of Dutch IVF centres. The participants were asked for their preferences at different success rates based on treatment trade-off scenarios. Finally, information on demographic, psychological and other predictors for treatment choice were collected.

Results: Complete data were obtained in 69 female patients (67%) and 27 physicians (49%). At a success rate for a life birth of 17% for both treatments, IVF in three natural cycles is preferred by 78% of the patients and physicians. Half of the patients and physicians still preferred natural cycle treatment at a success rate of 13%. Anxiety for hormone injections was the only significant predictor for patients' preferences.

Conclusion: There seems to be a latent demand for IVF in the natural cycle related to anxiety for hormone injections.     

Impact of overweight and underweight on IVF treatment in Chinese women

Objective.?To investigate the effects of body mass index (BMI) on ovarian stimulation and the outcome of IVF or ICSI treatment in Asian population who have different characteristics of BMI from white people.

Design.?In this retrospective study, the first fresh cycles of 1107 Chinese women were classified by BMI: underweight (BMI?<18.5?kg/m²), normal weight (BMI: 18.5–23.9?kg/m²) and overweight (BMI?≥?24?kg/m²). Dose and days of ovarian simulation, cancelled cycles and number of oocytes collected, fertilisation and embryo utilisation rates and pregnancy outcome were compared among BMI groups.

Results.?It showed that overweight women required more ampoules of gonadotrophin (P?=?0.002) and had lower peak oestradiol concentration (P?=?0.001), increased cycle cancellation due to insufficient follicle development (P?=?0.018) and a higher miscarriage rate (10.5 vs. 5.4%, P?=?0.018, OR?=?2.006 (95% CI: 1.09–3.69, P?=?0.025)) compared with normal weight women. However, no differences were found in clinical pregnancy and live-birth rates. Underweight compared with normal weight women showed no differences in ovarian stimulation and IVF outcome although the clinical pregnancy rate was lower (31.1 vs. 37.3%).

Conclusion.?At a lower cutoff point of BMI in Chinese women, overweight is associated with increased miscarriage risks and impaired response to ovarian stimulation after IVF and ICSI.     

The Added Value of Embryo Cryopreservation to Cumulative Ongoing Pregnancy Rates Per IVF Treatment: Is Cryopreservation Worth the Effort?

Purpose : To calculate the added benefit of a cryopreservation program to the cumulative ongoing pregnancy rate over a maximum of three cycles of IVF. Methods : A total of 1251 couples beginning their first IVF treatment between January 1995 and December 1999 were evaluated. Ongoing pregnancies from fresh and subsequent cryopreserved embryo transfer cycles were analyzed. Pregnancies arising from the cryopreservation cycle were considered to augment the cumulative pregnancy rate when no ongoing pregnancy arose from the fresh embryo transfer cycle. Results : The ongoing pregnancy rate per cryopreserved embryo transfer was 11.7%. The cumulative ongoing pregnancy rate following three successive started fresh IVF cycles was 42.5%. When pregnancies arising from the transfer of thawed cryopreserved embryos were included, the cumulative ongoing pregnancy rate increased to 43.8%, rising to 44.8% when extrapolated data from as yet unthawed embryos was included. Conclusions : When analyzed in these terms, the supplementary benefit of cryopreserving supranumerical embryos appears limited.     

Intracytoplasmic Sperm Injection and Conventional In Vitro Fertilization Are Complementary Techniques in Management of Unexplained Infertility

Purpose : To evaluate the role of ICSI in unexplained infertility. Methods : In 125 cycles with six or more oocytes retrieved per cycle, sibling oocytes were randomly allocated to IVF or ICSI (group A). In 74 cycles with less than six oocytes retrieved per cycle, cycles were allocated to IVF or ICSI (group B). Results : In group A, ICSI fertilization rate of 61% per allocated oocyte was higher than IVF fertilization rate of 51.6% (P < 0.001). Complete fertilization failure occurred in 19.2 and 0.8% of cycles in IVF and ICSI, respectively (P < 0.001). In group B, fertilization rate in IVF cycles was 53.3% as compared to 60.7% per allocated oocyte in the ICSI cycles (P = 0.29). Complete fertilization failure was higher (P = 0.02) in conventional IVF (34.3%) than ICSI cycles (10.3%). Conclusions : Allocation of sibling oocytes to IVF and ICSI in the first cycle minimizes risk of fertilization failure. For patients with limited number of oocytes, ICSI technique is recommended.     

Treatment Policy After Poor Fertilization in the First IVF Cycle

Purpose: The chance of recurrence of poor fertilization in a second in vitro fertilization (IVF) cycle was assessed. Methods: Total fertilization failure was defined, and the relationship between the fertilization rate and the number of motile sperm cells per milliliter of semen was assessed. Patients with a total fertilization failure or poor fertilization (20% or less of the oocytes fertilized) were divided into three subgroups with different chances of fertilization and were followed in a subsequent IVF cycle. Results: The recurrence rate of total fertilization failure was high in all three groups (45–70%), and poor fertilization frequently occurred in the second cycle (50–75%). Conclusions: Poor fertilization frequently recurs in the second IVF cycle. The use of intracytoplasmic sperm injection could be considered after fertilization of 20% or less of oocytes in the first cycle, irrespective of the number of motile sperm cells per milliliter of semen.