Succeeding Cycle Research Articles

Effects of letrozole cotreatment on endocrinology and follicle development in women undergoing ovarian stimulation in an antagonist protocol.

What are the downstream endocrine and paracrine consequences of letrozole (LZ) cotreatment during ovarian stimulation and is follicle growth and recruitment affected? Letrozole cotreatment induces marked changes in both the follicular and luteal phase endocrinology causing potentiation of follicle diameter and an improved corpus luteum function without affecting the secondarily recruited follicle cohort. Letrozole is a third-generation aromatase inhibitor that is well-established as an effective ovulatory agent, while its possible benefits in standard in vitro fertilization protocols are less thoroughly investigated. This study included a double-blinded, placebo-controlled, randomized study with LZ or placebo intervention during ovarian stimulation for IVF treatment, an observational preceding baseline natural cycle and a succeeding follow-up visit. Participants were enrolled between August 2016 and November 2018. Data from the randomized, stimulated cycle were part of a larger RCT, which was previously published. The study was conducted at a public fertility clinic at Herlev Hospital, Denmark, including 31 healthy, normo-responding women eligible for IVF treatment. They underwent a natural baseline cycle and were subsequently randomized to receive either LZ 5 mg (n = 16) or placebo (n = 15) daily during ovarian stimulation from cycle day (CD) 2-3 until induction of ovulation. Throughout both cycles, monitoring was performed every third day with transvaginal ultrasound for assessment of follicle count and diameter, and blood analyses for the determination of twelve endocrine and paracrine parameters. A follow-up assessment was performed at CD2-3 in the succeeding cycle. In the randomized part of the study, we determined differences in blood parameters, follicle recruitment, and follicle diameter. In the observational part of the study, we assessed follicle recruitment in between cycles and its correlation to endocrine parameters. Letrozole cotreatment significantly suppressed oestradiol (E2) concentrations in the follicular phase (area under the curve (AUC) -58% (95% CI [-70%; -43%], P < 0.001)) and luteal phase (AUC -39% [-63%; -1%], P = 0.046). This had a marked effect on the endocrine and paracrine output with increased follicular phase luteinizing hormone (AUC +37% [3%; 82%], P = 0.033), androstenedione (AUC +36% [6%; 74%], P = 0.016), testosterone (AUC +37% [7%; 73%], P = 0.013) and 17-OH-progesterone (AUC +114% [10%; 318%], P = 0.027). Furthermore, follicle-stimulating hormone (FSH) was increased at stimulation day 5 in the LZ group (P < 0.05). In the luteal phase, increased corpus luteum output was reflected by elevated progesterone (AUC +44% [1%; 104%], P = 0.043), inhibin A (AUC +52% [11%; 108%], P = 0.011), androstenedione (AUC +31% [9%; 58%], P = 0.006) and testosterone (AUC +29% [6%; 57%], P = 0.012) in the LZ group. The altered balance between oestrogens and androgens was reflected in a markedly reduced SHBG concentration in the LZ group throughout the luteal phase (AUC -35% [-52%; -11%], P = 0.009). Endocrine and paracrine parameters were similar between groups at the follow-up visit. Letrozole cotreatment significantly increased the mean number of follicles >16 mm at oocyte retrieval (7.2 vs 5.2, difference: 2.0, 95% CI [0.1; 3.8], P = 0.036), while the mean total number of follicles at oocyte retrieval was the same (23.7 vs 23.5, difference: 0.2 [-5.8; 6.1], P = 0.958), and the mean FSH consumption during the stimulated cycle was similar (1500 vs 1520 IU, difference -20 IU [-175; 136], P = 0.794). Between cycles, the mean antral follicle count at CD2-3 was unchanged (natural cycle 19.0, stimulated cycle 20.9, follow-up cycle 19.7, P = 0.692) and there was no effect of LZ cotreatment on the recruitment of the next follicle cohort (test for interaction, P = 0.821). This study included a relatively small, selected group of healthy women with an expected normal ovarian function and reserve, and the effects of LZ may therefore be different in other patient groups. We confirm some previous findings concerning increased follicle growth and increased endogenous FSH and androgen production, which support the rationale for further studies on the use of LZ cotreatment, for example, as a form of endogenous androgen priming sensitizing the follicle to FSH. Letrozole appears to improve the luteal phase with better stimulation of corpus luteum and progesterone secretion. The authors declare no conflicts of interest relating to the present work. NCT02939898.

The Burden of Surgical Cancellations: A Quality Improvement Study on the Importance of Preoperative Assessment.

BackgroundThe operating room (OR) is a critical facility that consumes a significant percentage of the hospital's resources, so it must be used judiciously. Surgical cancellation is a chief cause of OR underutilization. The purpose of this study was to hold medical concerns accountable for surgical cancellations at a large tertiary care hospital in Maharashtra, India.MethodsThe Plan, Do, Study, and Act (PDSA) cycle is a tool for analyzing change and learning via action. We used this method to determine the origins of errors, identify key points, and test change interventions such as an individually tailored anesthetic plan, provision of a pre-anesthesia evaluation clinic in the outpatient department, reevaluating patients, and rechecking the preoperative checklist. This study was undertaken as a part of a quality improvement project at our hospital in India. All elective surgical operations scheduled between January and November 2020 were included, and canceled procedures were investigated to identify potential reasons.ResultsDuring the auditing period, 7,709 elective operations were scheduled; 68 (0.88%) of them were canceled. After piloting interventions, the rate of cancellations dropped from 1.08% to 0.67% in the succeeding cycle. A root cause analysis of the data revealed that there was a 7.1% decrease in cancellations due to hypertension, a 3.8% decrease due to insufficient routine blood tests, and a 1.9% decrease in the inappropriate preoperative workup, while we saw an increase in fever (5.5%) and blood sugar level (1.9%) discrepancies.ConclusionsDr. D. Y. Patil Hospital & Research Centre in Pune, India, had cancellations in scheduled ORs due to associated medical co-morbidity that were potentially reducible post-intervention and could be replicated for application in various tertiary care hospitals. Regular monthly audits, quality improvement projects, and the designation of an organized system may enhance the proper utilization of the OR which could potentially save funds, preserve resources, alleviate the burden of patients, and reduce cancellations to a minimum.

Inside Mid-Triassic fluvial deposits: a legacy of mining sediment-hosted ore bodies in Cheshire, UK

In the Cheshire Basin the Mid-Triassic Helsby Sandstone Formation includes deposits of fluvial and aeolian origin. Sedimentological details of these deposits are commonly obscured in weathered outcrops but can be studied in unweathered sections in disused mines at the Alderley Edge Geological Site of Special Scientific Interest in northeast Cheshire. Fining-upward cycles seen in the fluvial units comprise channel-fill deposits that rest on an erosion surface, grade upwards from conglomerate to fine sandstone and are overlain by mudstones that underwent erosion at the initiation of the next cycle. The mudstone components of some cycles remain in parts of the mines but others were eroded completely and are now represented by concentrations of intraclasts in the succeeding cycle. Mudstone beds and those containing intraclasts formed complete and partial barriers to fluid movement respectively. Their effect on the migration and accumulation of intrastratal fluids is reflected by the form and disposition of voids left by the mining of ore bodies hosted by this facies. A corollary is that if the voids are interpreted as representing hydrocarbon accumulations, rather than ore bodies, reservoir situations analogous to those in the Helsby Sandstone in comparable structures in the East Irish Sea Basin may be viewed from a unique internal perspective.

Difference between even- and odd-numbered cycles in the predictability of solar activity and prediction of the amplitude of cycle 25

Abstract. It was shown previously that the sunspot number (SSN) at a point 3 years before the minimum is well correlated with the maximum SSN of the succeeding cycle, and a better correlation is obtained when the maximum SSN is replaced by the average SSN over a cycle for which the average SSN is calculated by dividing cycles at a point 3 years before the minimum (Yoshida and Yamagishi, 2010; Yoshida and Sayre, 2012). Following these findings, we demonstrate in this paper that the correlation between the SSN 3 years before the minimum and the amplitude of the coming cycle differs significantly between even-numbered and odd-numbered cycles: the correlation is much better for even-numbered cycles. Further, it is shown that the amplitude of even-numbered cycles is strongly correlated with that of the succeeding odd-numbered cycles, while the correlation between amplitudes of odd-numbered cycles and those of succeeding even-numbered cycles is very poor. Using the excellent correlations, we estimate the maximum SSN of the current cycle 24 at 81.3 and predict the maximum SSN of cycle 25 to be 115.4 ± 11.9. It is of note, however, that a peak of the SSN has been observed in February 2012 and the peak value 66.9 is considerably smaller than the estimated maximum SSN of cycle 24. We conjecture that the second higher peak of the SSN may appear.

In situ gasification and CO 2 separation using chemical looping with a Cu-based oxygen carrier: Performance with bituminous coals

This paper is concerned with the chemical looping combustion of coal in a technique whereby the fuel is gasified in situ using CO 2 in the presence of a batch of supported copper oxide (the “oxygen carrier”) in a single reactor. As the metal oxide becomes depleted, the feed of fuel is discontinued, the inventory of fuel is reduced by further gasification and then the contents are re-oxidised by the admission of air to the reactor, to begin the cycle again. A catalyst support, impregnated with a saturated solution of copper and aluminium nitrates, acted as a durable oxygen carrier over numerous cycles of reduction and oxidation, using air as the oxidant. Two bituminous coals (Taldinskaya, Russia, and Illinois No. 5, USA) were investigated and compared with a lignite (Hambach, Germany). The lignite was highly reactive and was gasified completely by 15 mol% CO 2 in N 2 at 1203 K and 1 bar, so that there was no build up of char in the bed. The bituminous coals produced chars much less reactive than the lignite char, so that there was a steady accumulation of char in the bed with number of cycles, with the degree of accumulation being dependent on the reactivity of the char. Since the kinetics of gasification by CO 2 of the chars from either bituminous coal were slow, their rates were controlled by intrinsic chemical kinetics and were not affected by the ability of the oxygen carrier to alter the rates of external mass transfer when gasification is rapid. However, it is likely that rates of gasification in the presence of the carrier are still larger than in its absence, owing to the overall lower [CO] present in the bulk of the fluidised bed during chemical looping. At the temperature used, the carrier was cycling between Cu and Cu 2O, since CuO is only stable if the partial pressure of O 2 exceeds 0.03 bar at 1203 K. The CuO decomposes to Cu 2O and O 2 relatively rapidly at these temperatures, once the oxygen concentration is effectively zero. It was impossible to ascertain in our experiments whether the oxygen so generated, after the switching of the air for nitrogen before the start of the succeeding cycle of gasification, made any substantial difference to the reactivity of the char present in the bed. The rate of oxidation of the carrier was found to be much more rapid than the rate of oxidation of the inventory of char. This allows a preferential oxidation of the carrier and most likely accounts for why progressively less CO and CO 2 is produced during successive cycles with short periods of oxidation: the increasingly reduced carrier reacts more rapidly than the char. There was no obvious impact from the sulphur contained in the fuels, but longer-term testing is needed. No agglomeration between the carrier particles and the ash was observed, despite the high temperatures during oxidation.

Predicting amplitude of solar cycle 24 based on a new precursor method

Abstract. It is shown that the monthly smoothed sunspot number (SSN) or its rate of decrease during the final years of a solar cycle is correlated with the amplitude of the succeeding cycle. Based on this relationship, the amplitude of solar cycle 24 is predicted to be 84.5±23.9, assuming that the monthly smoothed SSN reached its minimum in December 2008. It is further shown that the monthly SSN in the three-year period from 2006 through 2008 is well correlated with the monthly average of the intensity of the interplanetary magnetic field (IMF). This correlation indicates that the SSN in the final years of a solar cycle is a good proxy for the IMF, which is understood to reflect the magnetic field in the corona of the sun, and the IMF is expected to be smallest at the solar minimum. We believe that this finding illuminates a physical meaning underlying the well-known precursor method for forecasting the amplitude of the next solar cycle using the aa index at the solar minimum or its average value in the decaying phase of the solar cycle (e.g. Ohl, 1966), since it is known that the geomagnetic disturbance depends strongly on the intensity of the IMF. That is, the old empirical method is considered to be based on the fact that the intensity of the coronal magnetic field decreases in the late phase of a solar cycle in parallel with the SSN. It seems that the precursor method proposed by Schatten et al. (1978) and Svalgaard et al. (2005), which uses the intensity of the polar magnetic field of the sun several years before a solar minimum, is also based on the same physical phenomenon, but seen from a different angle.

THE PREDICTIVE POWER OF OHL'S PRECURSOR METHOD

Using linear regression techniques and correlation analysis, the predictive power of Ohl's method is shown to satisfy one of the following relationships. Either a successful prediction of cycle amplitude can be obtained if the correlation between the minimum aa geomagnetic index in the declining phase of a solar cycle and the sunspot maximum of the succeeding cycle becomes stronger, or the prediction error exceeds the expected prediction error if the correlation becomes weaker. The correlation coefficient has a declining secular variation, which leads to a weakening trend in predictive power, as well as a 44 year periodicity that may explain why the prediction method did not work well for solar cycle 23. As this finding only emerged twice in the ∼100 year period studied, this 44 year periodicity may occur with a degree of uncertainty and may therefore need to be checked in the future. Two quantities, namely a prediction parameter and the prediction index, are proposed to analyze predictive power. Using the above properties, the success probability of a prediction result can be analyzed in advance.

Blastomere Number and Pregnancy Rates in the Succeeding In Vitro Fertilization Cycle in Women Who Formed All Embryos with ≤5 Blastomeres

Background: Studies on single embryo transfer showed a marked decreased pregnancy rate following transfer of day 3 embryos with 4 or 5 blastomeres compared to those with 6-9 blastomeres. Objective: The objective of the present study was to determine the likelihood of subsequent IVF cycles showing no embryos having greater than 5 blastomeres. Furthermore the study would determine the relative difference in pregnancy rates and implantation rates when embryos with a maximum of 4 or 5 blastomeres were transferred vs. transfers with at least one embryo with 6 blastomeres. Materials and Methods: A 10 year retrospective review was made to identify women having a transfer with no day 3 embryos having 6 or more blastomeres on day 3. All stimulation protocols were used including minimal stimulation. There were no exclusions for serum FSH levels and some cases included serum FSH levels >100 mIU/mL. Viable pregnancy rates at 8 and 12 weeks were determined as well as live delivered pregnancy rates in subsequent cycles according to the group with less vs. more blastomeres. Results: There were 242 IVF cycles identified where the maximum number of embryos had 5 blastomeres. The clinical 8 and 12 week viable pregnancy rates were 24.8% (60/242) and 22.3% and the live delivered pregnancy rate was 21.1%. The implantation rate was 15.6%. There were 90 of the 191 women attempting another IVF cycle. The majority (82.2%) did attain at least one embryo with 6 blastomeres in the succeeding cycle as did 82% of 67 women attempting 3 or more cycles. The live delivered pregnancy rate for women having at least 1 embryo transferred in cycle 2 or greater with 6 blastomeres was 32.4% (42/129) vs. only 7.1% (2/28) with the maximum of 5 blastomeres per embryo (P<.01, Fisher's exact test). Conclusions: The majority of women with embryos with <5 blastomeres can do better in subsequent cycles. Those that do attain at least one embryo with 6 blastomeres have a reasonable live delivered pregnancy rate. Those who persist with embryos with only 4 or 5 blastomeres have a very low chance of achieving a successful pregnancy.

Optimal prediction of the peak of the next 11-year activity cycle and of the peaks of several succeeding cycles on the basis of long-term variations in the solar radius or solar constant

We propose a new technique for the optimal prediction of the peak of the next 11-year activity cycle prior to the cycle beginning and of the peaks of several succeeding cycles on the basis of long-term variations in the solar radius or solar constant. The method is based on the already established fact that the long-term cyclic variations of the activity, radius, and solar constant are correlated in both phase and amplitude, since they are caused by some common processes in the Sun. The peak of the succeeding cycle 24 is expected to have the height W max = 70 ± 10 (in units of relative sunspot number). The subsequent cycles 25 and 26, which will be formed during the descent of the current secular cycle, will have still lower peaks with the heights W max = 50 ± 15 and W max = 35 ± 20.

Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer: Clinical parameters: Bruchovsky N, Klotz L, Crook J, Malone S, Ludgate C, Morris WJ, Gleave ME, Goldenberg SL, The Prostate Center at Vancouver General Hospital, Division of Urology, Department of Surgery, University of British Columbia,

Background This prospective Phase II study was undertaken to evaluate intermittent androgen suppression as a form of therapy in men with localized prostate cancer who failed after they received external beam irradiation. Methods Patients who demonstrated a rising serum prostate-specific antigen (PSA) level after they received radiotherapy and who were without evidence of distant metastasis were accepted into the study. Treatment in each cycle consisted of cyproterone acetate given as lead-in therapy for 4 weeks, followed by a combination of leuprolide acetate and cyproterone acetate, which ended after a total of 36 weeks. Results Of 109 patients registered, 103 patients were eligible for interruption of treatment, yielding a PSA response rate of 95%. The study continued for 6 years with a mean follow-up of 3.7 years (median follow-up, 4.2 years). The time off treatment averaged 53% of the total cycle time but, in absolute terms, decreased with each succeeding cycle, ranging from 63.7 weeks in Cycle 1 to 25.6 weeks in Cycle 5. Prostate volume was reduced by 40% in Cycle 1 and by 34% in Cycle 2, and there were no decreases in Cycle 3 or Cycle 4. At the end of the trial, 38.5% of patients still were receiving treatment, 23.9% of patients had failed, and 15.6% of patients had died. Only 2% of deaths were cancer-specific. Conclusions Biochemical recurrence after irradiation for localized prostate cancer was amenable to cyclic androgen withdrawal therapy and showed a high response rate. Despite progressively shorter treatment cycles, the off-treatment interval remained appreciable, ranging from 65% in Cycle 1 to 46% in Cycle 5.

Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer

This prospective Phase II study was undertaken to evaluate intermittent androgen suppression as a form of therapy in men with localized prostate cancer who failed after they received external beam irradiation. Patients who demonstrated a rising serum prostate-specific antigen (PSA) level after they received radiotherapy and who were without evidence of distant metastasis were accepted into the study. Treatment in each cycle consisted of cyproterone acetate given as lead-in therapy for 4 weeks, followed by a combination of leuprolide acetate and cyproterone acetate, which ended after a total of 36 weeks. Of 109 patients registered, 103 patients were eligible for interruption of treatment, yielding a PSA response rate of 95%. The study continued for 6 years with a mean follow-up of 3.7 years (median follow-up, 4.2 years). The time off treatment averaged 53% of the total cycle time but, in absolute terms, decreased with each succeeding cycle, ranging from 63.7 weeks in Cycle 1 to 25.6 weeks in Cycle 5. Prostate volume was reduced by 40% in Cycle 1 and by 34% in Cycle 2, and there were no decreases in Cycle 3 or Cycle 4. At the end of the trial, 38.5% of patients still were receiving treatment, 23.9% of patients had failed, and 15.6% of patients had died. Only 2% of deaths were cancer-specific. Biochemical recurrence after irradiation for localized prostate cancer was amenable to cyclic androgen withdrawal therapy and showed a high response rate. Despite progressively shorter treatment cycles, the off-treatment interval remained appreciable, ranging from 65% in Cycle 1 to 46% in Cycle 5.

An ichnofabric approach to the depositional interpretation of the intensely burrowed Bateig Limestone, Miocene, SE Spain

The foraminiferal-rich pelagic Bateig Limestone forms several varieties of the important building stones quarried at Bateig Hill in southeastern Spain. Three principal ichnofabrics ( Bichordites, mottled- Palaeophycus and mottled- Ophiomorpha) are recognized, which are present in at least two (possibly up to four) repeated successions (cycles). Each succession begins with an erosional event. The Bichordites ichnofabric represents a new type of facies, formed as thin turbidity/grain flow, stratiform units derived from sediment slips off a fault into deep water. Each slipped unit became almost completely bioturbated by infaunal echinoids, colonizing by lateral migration. Because of the thinness of the units, successive colonizations tended to truncate the underlying burrows giving rise to a pseudo-stratification. As the Bichordites ichnofabric accumulated on the fault apron, thus reducing the effective height of the fault scarp, the substrate gradually came under the influence of currents traversing the shelf. This led to a change in hydraulic regime, and to the mottled- Palaeophycus and mottled- Ophiomorpha ichnofabrics in sediment deposited under bed load transport, and associated with laminar and cross-stratified beds and local muddy intervals. Reactivation of the fault triggered erosion and channeling and a return to grain flow sedimentation, and to the Bichordites ichnofabric of the succeeding cycle. The highest unit of the Bateig Limestone is formed entirely of cross-stratified calcarenites with occasional Ophiomorpha ( Ophiomorpha-primary lamination ichnofabric) and is similar to many shallow marine facies but they still bear a significant content of pelagic foraminifera. The sedimentary setting bears resemblance with that described for the Pleistocene Monte Torre Paleostrait and the modern Strait of Messina (Italy), where the narrow morphology of the depositional area enhanced tidal currents and allowed for high-energy sandy deposition in relatively deep areas. More data on the Miocene paleogeography of the Bateig area should provide further testing for this hypothesis. The ichnofacies and stacking of the Bateig Limestone differ from the classic Seilacherian model in that they reflect changes in hydraulic process and are associated with faulting and subsidence and changes in sediment supply. Recognition of the unusual ichnofabrics and their relationships provides a clear indication of the overall dynamic setting.

Cortical recruitment of nonmuscle myosin II in early syncytial Drosophila embryos

The nuclei of early syncytial Drosophila embryos migrate dramatically toward the poles. The cellular mechanisms driving this process, called axial expansion, are unclear, but myosin II activity is required. By following regulatory myosin light chain (RLC)–green fluorescent protein dynamics in living embryos, we observed cycles of myosin recruitment to the cortex synchronized with mitotic cycles. Cortical myosin is first seen in a patch at the anterocentral part of the embryo at cycle 4. With each succeeding cycle, the patch expands poleward, dispersing at the beginning of each mitosis and reassembling at the end of telophase. Each cycle of actin and myosin recruitment is accompanied by a cortical contraction. The cortical myosin cycle does not require microtubules but correlates inversely with Cdc2/cyclinB (mitosis-promoting factor) activity. A mutant RLC lacking inhibitory phosphorylation sites was fully functional with no effect on the cortical myosin cycle, indicating that Cdc2 must be modulating myosin activity by some other mechanism. An inhibitor of Rho kinase blocks the cortical myosin recruitment cycles and provokes a concomitant failure of axial expansion. These studies suggest a model in which cycles of myosin-mediated contraction and relaxation, tightly linked to Cdc2 and Rho kinase activity, are directly responsible for the axial expansion of the syncytial nuclei.

Mechanisms for lateral turns in lamprey in response to descending unilateral commands: a modeling study.

Straight locomotion in the lamprey is, at the segmental level, characterized by alternating bursts of motor activity with equal duration and spike frequency on the left and the right sides of the body. Lateral turns are characterized by three main changes in this pattern: (1) in the turn cycle, the spike frequency, burst duration, and burst proportion (burst duration/cycle duration) increase on the turning side; (2) the cycle duration increases in both the turn cycle and the succeeding cycle; and (3) in the cycle succeeding the turn cycle, the burst duration increases on the non-turning side (rebound). We investigated mechanisms for the generation of turns in single-segment models of the lamprey locomotor spinal network. Activation of crossing inhibitory neurons proved a sufficient mechanism to explain all three changes in the locomotor rhythm during a fictive turn. Increased activation of these cells inhibits the activity of the opposite side during the prolonged burst of the turn cycle, and slows down the locomotor rhythm. Secondly, this activation of the crossing inhibitory neurons is accompanied by an increased calcium influx into the cells. This gives a suppressed activity on the turning side and a contralateral rebound after the turn, through activation of calcium-dependent potassium channels.

Contralateral ovulation shortens follicular phase length and favours pre-embryo development during ovarian stimulation with clomiphene citrate.

The present study was undertaken to evaluate whether the site of ovulation affects the following follicular phase length and pre-embryo development during infertility treatment with ovarian stimulation using clomiphene citrate. A total of 363 cycles in 97 patients undergoing infertility treatment (182 intrauterine insemination (IUI) cycles in 60 patients and 181 in-vitro fertilization (IVF) cycles in 52 patients) were studied. The cycles were divided into two main groups: preceding unilateral ovulation (PUO) and preceding bilateral ovulation (PBO). In the PUO group, the cycles were subdivided into contralateral ovulation, bilateral ovulation and ipsilateral ovulation. In IVF cycles alone, bilateral ovulations were further divided into bilateral ovulation-contralateral side and bilateral ovulation, ipsilateral side. Contralateral ovulations were seen in 134 of 240 cycles (56%), excluding bilateral ovulation and PBO. The follicular phase length in contralateral ovulation (16.2 +/- 2.6 days, mean +/- SD) was significantly (P < 0.05) shorter than that of ipsilateral ovulation (16.9 +/- 2.8). There were no significant differences of follicular phase length among contralateral ovulation, bilateral ovulation and PBO. Of IVF cycles including contralateral ovulation-ipsilateral ovulation and bilateral ovulation a total of 107 preovulatory follicles was assessed in the contralateral side (contralateral ovulation + bilateral ovulation-contralateral side) and 97 in the ipsilateral side (ipsilateral ovulation + bilateral ovulation, ipsilateral side). The oocyte retrieval rate (88%), fertilization rate (84%), cleavage rate (95%), embryo transfer rate (70%) of contralateral follicles were higher than those of ipsilateral follicles (71, 62, 86, 38% respectively) and those of PBO (76, 62, 87, 41% respectively). The total pregnancy rate of both IUI and IVF did not differ among contralateral ovulation (15%), ipsilateral ovulation (8%), bilateral ovulation (11%) and PBO (10%). The results confirm and extend our previous findings in natural cycles, suggesting that local ovarian factors, e.g. from corpus luteum, affect the health of preovulatory follicle and the enclosed oocyte in the same ovary (ipsilateral) negatively. Contralateral selection of preovulatory follicles in the succeeding cycle shortens the follicular phase length and favours pre-embryo development. The chance of conceiving during ovarian stimulation with clomiphene citrate may thus be affected by the site of ovulation in the previous cycle.

Contralateral selection of dominant follicle favours pre-embryo development.

Ovulation was studied using vaginosonography in a total of 410 natural cycles of 123 women undergoing infertility treatment [267 intrauterine insemination (IUI) cycles of 103 women and 143 in-vitro fertilization (IVF) cycles of 50 women]. None of the women received ovarian stimulation. Each follicle was measured daily from 14 mm in diameter until formation of corpus luteum or oocyte retrieval. Contralateral ovulation as compared with the preceding cycle occurred in 57% of the 410 cycles. Contralateral ovulations occurred in 72% of cycles with a follicular phase < 13 days. In cycles with a follicular phase of > 14 days, ovulations occurred at random. The length of follicular phase in contralateral ovulation cycles (15.2 +/- 3.2 days) was significantly (P < 0.05) shorter than that of ipsilateral ovulation cycles (15.8 +/- 2.8). During the 57% contralateral ovulations in 143 IVF cycles, the rates of oocyte retrieval (89%), fertilization (69%), cleavage (90%) and embryo transfer (56%) were significantly higher than those of ipsilateral ovulations (69, 51, 64 and 23% respectively). The pregnancy rate of contralateral ovulations (9%) was also higher, though not significantly, than that of ipsilateral ovulations (3%), although the pregnancy rates per transfer were similar (16 and 14% respectively). The total pregnancy rate of both IUI and IVF was higher in contralateral than in ipsilateral ovulation cycles (8.1 and 4.0% respectively). The dominant follicles in contralateral ovulation cycles showed significantly higher oestradiol/androstenedione ratio (P < 0.025) and oestradiol/testosterone + androstenedione ratio (P < 0.025) and lower androstenedione (P < 0.05) than those of ipsilateral ovulation cycles. There was no significant difference in oestradiol, progesterone and testosterone. These results indicate that the dominant follicles in contralateral ovulation cycles are healthier than those of ipsilateral ones. Local intra-ovarian factors, e.g. from the corpus luteum, may negatively affect the health of the dominant follicle and the enclosed oocyte. Therefore contralateral selection of the dominant follicle in the succeeding cycle may favour pre-embryo development. The chance of conceiving during a natural cycle may be affected by the site of ovulation in the preceding cycle.

Intravascular infusion of lipid into ewes stimulates production of progesterone and prostaglandin.

Effects of infusion of a lipid emulsion into ewes during mid-to late diestrus on serum concentrations of total cholesterol (TC), progesterone (P4), prostaglandin (PG) F2 alpha metabolite (PGFM), and PGE2, and on ovulation rate were examined. In experiment 1, ewes received infusions of either saline (S, n = 3) or soybean oil emulsion (SB, n = 3) for 5 h on each of Days 9-13 of the estrous cycle. In experiment 2, ewes received infusions of either S (n = 4), SB (n = 5), or olive oil emulsion (OO, n = 5) for 5 h on each of Days 9 through 15 of the estrous cycle. In both experiment 1 and experiment 2, infusion of lipid increased serum concentrations of TC and P4, which declined with time after infusion was terminated (treatment x hour interaction, experiment 1: TC, p < 0.01, P4, p < 0.01; experiment 2: TC, p < 0.01, P4, p < 0.001). Serum PGFM and PGE2 concentrations were greater in lipid-infused ewes than in controls on Days 13 through 15 (treatment x hour interaction; p < 0.03, p < 0.001, respectively). Duration of the estrous cycle was shortened in OO-infused ewes (16.2 +/- 0.4 days) compared with that of SB- and S-infused ewes (17.2 +/- 0.2 and 18.0 +/- 0.0 days, respectively; p < 0.01). Numbers of corpora lutea and follicles, and diameter of follicles > 4 mm did not differ among treatment groups on Day 14 of the succeeding cycle after infusion. These data indicate that lipid infusion stimulated increases in serum concentrations of TC, P4, and prostaglandins and may shorten the estrous cycle.

The effect of follicle maturing drugs on side of ovulation in successive cycles.

Our previous study has demonstrated that ovulation in unstimulated cycles is random with an equal likelihood of ipsilateral or contralateral ovulation occurring in the following cycle. This study evaluated women taking ovulation-inducing drugs to see if the side of ovulation in the preceding cycle has an influence on the side of ovulation in the succeeding cycle. Ovulatory patterns in consecutive pairs of cycles in anovulatory women treated with ovulation-inducing drugs were evaluated through sonographic studies of follicular maturation. The results demonstrated that when unilateral ovulation occurred, there was an equal likelihood of ipsilateral or contralateral ovulation in the succeeding cycle. However, ovulation-inducing drugs increase the incidence of bilateral or multiple ovulation.

Ipsilateral Versus Contralateral Ovary Selection of Dominant Follicle in Succeeding Cycle

There is still confusion as to whether ovulation in a succeeding cycle is a random event or is more likely to occur at the ipsilateral or contralateral ovary. Both histologic and sonographic data support alternating ovulation. Some ultrasound studies have suggested that ipsilateral ovulation is more likely in succeeding cycles, and another found right-sided ovulation to be more common. Because many of the studies are based upon small numbers, we initiated a large study to determine the more likely side of ovulation. Furthermore, the present investigation attempted to confirm biochemically the true existence of the dominant follicle by demonstrating appropriate serum estradiol levels. Evaluation of natural cycles (286 pairs) demonstrated 52.4% ipsilateral ovulation and 47.6% contralateral ovulation. Right-sided ovulation occurred in 54.5% of cycles. Our data suggest that the side of ovulation in successive cycles is not influenced by the side of ovulation in the preceding cycle.

Response of the bovine corpus luteum to increased secretion of luteinizing hormone induced by exogenous gonadotropin releasing hormone

Two experiments were conducted to investigate the response of the bovine corpus luteum to surges of luteinizing hormone (LH) induced by natural gonadotropin-releasing hormone (GnRH) administered twice during the same estrous cycle. In experiment 1, eight mature beef cows, each cow serving as her own control, were injected intravenously (iv) with saline on days 2 and 8 of the cycle (day of estrus = day 0 of the cycle), then with 100 μg GnRH on days 2 and 8 of the subsequent cycle. Jugular blood samples were taken immediately prior to an injection and at 15, 30, 45, 60, 120 and 240 min postinjection, to quantitate changes in serum luteinizing hormone. Blood was also collected on alternate days after an injection until day 16 of the cycle, to characterize changes in serum progesterone concentrations. Although exogenous GnRH caused release of LH on days 2 and 8 of the cycle, the quantity of LH released was greater on day 8 (P<.025). Serum levels of progesterone after treatment with GnRH on day 8 of the cycle did not differ significantly from those observed during the control cycles of the heifers. Because exposure of the bovine corpus luteum to excess LH, induced by GnRH early during the estrous cycle, causes attenuated progesterone secretion during the same cycle, these data suggest that a second surge of endogenous LH may ameliorate the suppressive effect of the initial release of LH on luteal function. Duration of the estrous cycle was not altered by treatment (control, 20.4 ± .5 vs. treated, 20.4 ± .4 days). In experiment 2, five mature beef cows, each serving as her own control, were injected iv with saline on days 2 and 8 of the estrous cycle. After an intervening cycle of normal duration, cows were injected iv with 100 μg GnRH on days 2 and 8 of the succeeding cycle. Corpora lutea were obtained per vaginam on day 10 of each cycle. Luteal tissue was sliced and incubated for 2 hr with saline (control) or LH (10 ng/ml). Treatment of cows with GnRH on days 2 and 8 caused a significant increase in in vitro basal progesterone production (μg/g) by luteal slices (control, 37.45 ± 2.93 vs. GnRH days 2 and 8, 53.18 ± 3.03) but suppressed the ability of luteal tissue to respond to LH (P<.07). Results of this latter experiment suggest that a second surge of GnRH-induced LH secretion on day 8 of the cycle promoted an increase in basal progesterone production but desensitized luteal cells to further stimulation by the gonadotropin.