Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13 000 autologous cycles reported to SART CORS.

STUDY QUESTION: After an IVF cycle cancellation, does changing the stimulation protocol affect the odds of live birth and recurrent cancellation in the subsequent cycle? SUMMARY ANSWER: After IVF cycle cancellation, compared to those who repeated the same stimulation protocol, those who changed their protocol had higher odds of live birth and lower odds of recurrent cycle cancellation. WHAT IS KNOWN ALREADY: There is limited data addressing the effect of changing the stimulation protocol after an IVF cycle is cancelled during initial stimulation. The odds of live birth outcomes are not known so far in studies addressing the effect of changing the protocol. STUDY DESIGN, SIZE, DURATION: Retrospective Cohort Study using the 2014-2017 Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. PARTICIPANTS/MATERIALS, SETTING, METHODS: The data included 13 135 patients with a first autologous IVF cycle that resulted in a cycle cancellation and was followed by a second autologous cycle within the study period. We excluded fertility preservation cycles, supernumerary cycle attempts after the second IVF cycle attempt, and cycles with more than one stimulation protocol documented per cycle start. Patients who received the same protocol for both cycles (n = 6434) were compared to those who changed their protocol in the second cycle (n = 6701). Multivariable logistic regression analyses were performed to estimate the adjusted odds of live birth and recurrent cancellation. MAIN RESULTS AND THE ROLE OF CHANCE: Changing the protocol in the second cycle resulted 14% lower odds of recurrent cycle cancellation (P = 0.01) and 17% higher odds of live birth after fresh transfers (P = 0.04). When stratifying the data by specific combinations of protocol change (agonist flare, agonist suppression, antagonist), there was an increase in live birth when switching from antagonist to agonist suppression (odds ratio (OR) = 1.36, P = 0.03) and from agonist suppression to antagonist (OR = 1.73, P = 0.01) compared to those who repeated their same stimulation protocol. Specifically in poor responders, outcomes were worse when using the agonist flare protocol and significantly improved with the agonist suppression protocol. LIMITATIONS, REASONS FOR CAUTION: Comparison of response to stimulation between first and second cycles cannot be made in this study because the index IVF cycle was cancelled during ovarian stimulation, and thus there is no reportable outcome data for that cycle. Additionally, SART only tracks the three stimulation protocols addressed in this study and does not have data on more contemporary protocols that are used in poor responders thus limiting the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: Using the SART CORS database, which includes >90% of all reported IVF cycles in the USA, provides generalizability to the demographically diverse IVF populations found here. In agreement with prior studies assessing change in IVF protocols, the agonist flare protocol seems to result in worse IVF outcomes, and based on our results, we believe that there is no role for the agonist flare protocol in patients with a prior poor response to stimulation. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: N/A.

Extreme tunability of interactions in a 7Li Bose-Einstein condensate.

We use a Feshbach resonance to tune the scattering length a of a Bose-Einstein condensate of 7Li in the |F=1,mF=1> state. Using the spatial extent of the trapped condensate, we extract a over a range spanning 7 decades from small attractive interactions to extremely strong repulsive interactions. The shallow zero crossing in the wing of the Feshbach resonance enables the determination of a as small as 0.01 Bohr radii. Evidence of the weak anisotropic magnetic dipole interaction is obtained by comparison with different trap geometries for small a.

Temporal extent of surface potentials between closely spaced metals.

Variations in the electrostatic surface potential between the proof mass and electrode housing in the space-based gravitational wave mission Laser Interferometer Space Antenna (LISA) is one of the largest contributors of noise at frequencies below a few mHz. Torsion balances provide an ideal test bed for investigating these effects in conditions emulative of LISA. Our apparatus consists of a Au coated Cu plate brought near a Au coated Si plate pendulum suspended from a thin W wire. We have measured a white noise level of 30 microV/sqrt Hz above approximately 0.1 mHz, rising at lower frequencies, for the surface potential variations between these two closely spaced metals.

Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals.

Meiosis is a double-division process that is preceded by only one DNA replication event to produce haploid gametes. The defining event in meiosis is prophase I, during which chromosome pairs locate each other, become physically connected, and exchange genetic information. Although many aspects of this process have been elucidated in lower organisms, there has been scant information available until now about the process in mammals. Recent advances in genetic analysis, especially in mice and humans, have revealed many genes that play essential roles in meiosis in mammals. These include cell cycle-regulatory proteins that couple the exit from the premeiotic DNA synthesis to the progression through prophase I, the chromosome structural proteins involved in synapsis, and the repair and recombination proteins that process the recombination events. Failure to adequately repair the DNA damage caused by recombination triggers meiotic checkpoints that result in ablation of the germ cells by apoptosis. These analyses have revealed surprising sexual dimorphism in the requirements of different gene products and a much less stringent checkpoint regulation in females. This may provide an explanation for the 10-fold increase in meiotic errors in females compared with males. This review provides a comprehensive analysis of the use of genetic manipulation, particularly in mice, but also of the analysis of mutations in humans, to elucidate the mechanisms that are required for traverse through prophase I.

Full- or half-cycle treatment of severe premenstrual syndrome with a serotonergic antidepressant.

Evidence that serotonergic antidepressants are effective for treating premenstrual syndrome (PMS) raises the question of whether dosing only in the symptomatic premenstrual phase is effective for this disorder. This preliminary randomized, double-blind study compared the responses to half-cycle or full-cycle dosing of sertraline in 31 patients who completed a preceding double-blind, short-term treatment trial. The subjects fulfilled criteria for severe PMS when they entered the preceding controlled trial. At the end of the short-term treatment trial, the double-blind was not broken; both improved and unimproved subjects were randomized in a double-blind fashion to receive either full-cycle or half-cycle sertraline in the 3-month extension study. Results showed that the total premenstrual scores from the Penn Daily Symptom Report (DSR) were lower in the half-cycle dosing group in each of the 3 treatment months but did not differ with statistical significance from the full-cycle dosing group. Further analysis of the 17 DSR items showed that mood swings, nervous tension, feeling out of control, and confusion were significantly lower (p < 0.05) at endpoint in the half-cycle dosing group. Overall, subjects who improved in prior treatment remained improved; approximately half the subjects who were unimproved at entry into the extension study improved, regardless of the dosing regimen. The results add support to other preliminary reports of efficacy of serotonergic antidepressants administered premenstrually and indicate the clinical importance of determining an optimal dose/benefit ratio of serotonergic antidepressants for PMS patients.

Localization of the steroidogenic acute regulatory protein in human tissues.

The rate-limiting step in steroid hormone production in the adrenal cortex and gonads, the translocation of cholesterol from the outer to the inner mitochondrial membranes, is mediated by the steroidogenic acute regulatory protein (StAR). Heretofore, the localization of StAR in human adult and fetal tissues has not been defined. To this end, expression of StAR was detected in formalin-fixed, paraffin-embedded specimens using a polyclonal antiserum raised against recombinant human StAR. Primordial follicles of adult ovaries did not contain StAR, whereas antral follicles stained intensely in the thecal layer, with occasional staining of granulosa cells. Corpora lutea were intensely stained, but with a patchy distribution. Corpora albicantia did not stain. A luteoma of pregnancy stained with patches of moderate intensity. Ovaries with hyperthecosis contained areas of intense thecal staining. An ovarian Leydig cell tumor stained intensely, whereas granulosa cell tumors were negative. Ovarian adenocarcinomas, borderline tumors, teratomas, cystadenomas, and a Brenner tumor displayed no specific StAR immunostaining. Testicular Leydig cells stained moderately to intensely, as did a testicular Leydig cell tumor. Sertoli cells stained weakly in some specimens. Seminomas and testicular germ cell tumors were negative. There was minimal to moderate staining in the adrenal glomerulosa and faciculata and minimal staining in the reticularis, while the medulla was negative. Adrenal cortical adenomas, hyperplasias, and carcinomas all contained areas of StAR staining. The renal distal tubules stained with moderate to marked intensity. Renal carcinomas had occasional modest staining. No immunostaining was found in the placenta. Fetal ovaries contained sporadic stromal cells displaying intense StAR staining, particularly in the hilar region. Oocytes from a 32-week fetal ovary showed moderate to intense staining. Fetal testes displayed intense Leydig cell staining. The neocortex of the fetal adrenal glands displayed only minimal StAR staining, whereas moderate to intense staining was found in the fetal zone. The fetal kidneys had moderate StAR staining of the distal convoluted tubules. We conclude that StAR is localized to normal and neoplastic cells in the gonads and adrenal cortex, which produce large amounts of pregnenolone. StAR protein was not detected in the placenta, documenting that placental progestin synthesis occurs through StAR-independent mechanisms. The presence of StAR in cells that do not express cholesterol side-chain cleavage enzyme cytochrome P450, including renal distal tubules, Sertoli cells, and fetal oocytes, suggests that StAR has roles in metabolic processes in addition to stimulating pregnenolone synthesis.