Aromatase inhibitors in stimulated IVF cycles

Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol level

Developmental stage on day-5 and fragmentation rate on day-3 can influence the implantation potential of top-quality blastocysts in IVF cycles with single embryo transfer

BACKGROUND: In IVF-ICSI cycles with single embryo transfer (SET), embryo selection for transfer is of crucial importance. The present study aimed to define which embryo parameters might be related to the implantation potential of advanced blastocysts. METHODS: Overall, in 203 cycles with SET, developmental characteristics of 93 implanted (group A) and 110 non-implanted (group B) advanced blastocysts of good quality were compared. The following developmental parameters were assessed in the two groups: normal fertilization, developmental stage on day 5, number of blastomeres on day 2 and on day 3, fragmentation rate on day 3, compaction on day 4 and cleavage pattern on day 2 and day 3. RESULTS: Expanded blastocysts compared to full blastocysts have higher implantation potential (56.5% vs. 29.3%, p < 0.05). In group B, a higher proportion of advanced blastocysts showed between 10% and 50% anucleated fragments on day 3 than in group A (23.6 vs 11.8, P = 0.03). Advanced blastocysts with >10–50% fragments on day 3 showed a significant lower implantation (29.7%) than those with ≤ 10%fragments (49.4%, P = 0.03). All the other parameters analysed were comparable for the two groups. CONCLUSION: Developmental stage on day 5 and fragmentation rate on day 3 were related to the implantation potential of advanced blastocysts and should also be taken into account in the selection of the best advanced blastocyst for transfer

New algorithm for OHSS prevention

Ovarian hyperstimulation syndrome (OHSS) still remains a life-threatening complication of in vitro fertilization treatment (IVF), keeping patients and especially those, who previously experienced OHSS, from attempting infertility treatment and childbearing. The recent implementation of four new modalities: the GnRH antagonist protocol, GnRH agonist (GnRHa) triggering of ovulation, blastocyst transfer and embryo/oocyte vitrification, renders feasible the elimination of OHSS in connection with ovarian hyperstimulation for IVF treatment. The proposed current algorithm is based on the number of follicles developed after ovarian stimulation, setting a cut-off level at the development of 18 or more follicles. Further, fulfilling this criterion, the algorithm is based on four decision-making points: the final day of patient work-up, the day of triggering final oocyte maturation, day-1 post oocyte pick-up (OPU) and day-5 post OPU

Aromatase inhibitors in post-menopausal endometriosis

Postmenopausal endometriosis is a rare clinical condition. The diagnosis and treatment of an endometriotic lesion in postmenopausal women is complicated. First line treatment choice should be surgical, given that there is a potential risk of malignancy. Medical treatment may be considered as second line or as an alternate first line treatment whenever surgery is contradicted and aims to alter the hormonal pathway leading to endometriosis progress. Different hormonal regimens have been administered to these patients, with conflicting however results. Aromatase inhibitors (AIs) represent one of the most recently used drugs for postmenopausal endometriosis. Clinical data for the use of (AIs) in postmenopausal patients is scarce. Up to date only 5 case reports are available regarding the use of these agents in postmenopausal women. Although definite conclusions may be premature, AIs appear to considerably improve patients' symptoms and reduce endometriotic lesions size. Nonetheless the subsequent induced reduction in estrogen production, leads to certain short-term and long-term adverse effects. Despite the limited available data, AIs appear to represent a new promising method which may improve symptoms and treat these patients, either as first line treatment, when surgery is contraindicated or as a second line for recurrences following surgical treatment. However, careful monitoring of patients' risk profile and further research regarding long-term effects and side-effects of these agents is essential prior implementing them in everyday clinical practice

Obstetric outcomes after treatment of periodontal disease during pregnancy: systematic review and meta-analysis

Objective To examine whether treatment of periodontal disease with scaling and root planing during pregnancy is associated with a reduction in the preterm birth rate

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

A Proof-of-Concept Clinical Trial of A Single Luteal Use of Long-Acting Gonadotropin-Releasing Hormone Antagonist Degarelix in Controlled Ovarian Stimulation for In Vitro Fertilization: Long Antagonist Protocol

IntroductionA drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in in vitro fertilization (IVF) is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017.Materials and methodsThe efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients. In the first part, five healthy oocyte donors underwent ovarian stimulation with this new protocol: in the late luteal phase, at day 24, a bolus injection of degarelix was administered subcutaneously to control the LH surge in the follicular phase. Ovarian stimulation with gonadotropins was initiated subsequently from day 7 to day 10. End points were first to inhibit the LH surge later in the follicular phase and, second, to retrieve mature oocytes for IVF. In the second part, five infertile women received the same bolus injection of degarelix administered during the luteal phase at day 24. Different gonadotropin starting days (day 2 through day 8) were tested in order to observe possible differences in ovarian stimulation. In these infertile patients, fresh embryo transfers were performed to assess the pregnancy efficacy of this protocol on pregnancy outcomes and to address any possible negative effects on endometrium receptivity.ResultsIn the first part of the study, all donors were effectively downregulated with a single luteal dose of 0.5 ml of degarelix for up to 22 days until the final oocyte maturation triggering day. Mature oocytes were retrieved after 36 h from all patients and all produced 2–7 blastocysts. In the second part, all five infertile patients achieved sufficient LH downregulation and completed ovarian stimulation without any LH surge. All patients (except one with freeze all strategy) had blastocysts transferred and pregnancy occurred in three out of five women.ConclusionA single dose of the long-acting antagonist degarelix during the luteal phase appears to be effective in downregulating hypophysis during ovarian stimulation. This represents a possible new protocol for IVF, which should be further elucidated in RCTs

Aromatase inhibitors in stimulated IVF cycles

Abstract Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels</p

Ovarian Stimulation with FSH Alone versus FSH plus a GnRH Antagonist for Elective Freezing in an Oocyte Donor/Recipient Programme: A Protocol for a Pilot Multicenter Observational Study

Preliminary data have shown that it is possible to attempt in vitro fertilization (IVF) treatment in fresh cycles without the use of a gonadotropin-releasing hormone (GnRH) antagonist or any other medication to prevent the luteinizing hormone (LH) surge during ovarian stimulation. To date, there is no information on this topic in the context of a prospective controlled trial. However, as prevention of the LH surge is an established procedure in fresh cycles, the question is whether such a study can be performed in frozen cycles. We aim to perform a pilot study in order to compare the efficacy of a protocol using FSH alone with that of a protocol using follicle-stimulating hormone (FSH) plus a GnRH antagonist for controlled ovarian hyperstimulation (COH) in cycles of elective freezing in the context of a donor/recipient program. This is a seven-center, two-arm prospective pilot cohort study conducted at the respective Assisted Reproductive Units in Greece. The hypothesis to be tested is that an ovarian stimulation protocol that includes FSH alone without any LH surge prevention regimens is not inferior to a protocol including FSH plus a GnRH antagonist in terms of the clinical outcome in a donor/recipient model. The results of the present study are expected to show whether the addition of the GnRH antagonist is necessary in terms of the frequency of LH secretory peaks and progesterone elevations >1 ng/mL during the administration of the GnRH antagonist according to the adopted frequency of blood sampling in all Units