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In recent years, social and cultural trends have resulted in women delaying childbirth, thereby leading to reproductive senescence as a growing public health problem. We discuss potential etiologies for age-related female reproductive decline. We bring supportive evidence to the central role of mitochondrial dysfunction and oxygen radicals in the process of aging in general and reproductive senescence specifically. We also explore the role of coenzyme Q10 deficiency as a contributing factor and the effects of its administration. [ABSTRACT FROM AUTHOR]

The second installment in our two-part article on AIs looks at these agents as potential alternatives to clomiphene citrate and gonadotropins for stimulating fertility in breast cancer survivors. [ABSTRACT FROM AUTHOR]

With new research showing that aromatase inhibitors can dramatically cut the risk of recurring breast cancer, patients will probably have many questions about drugs like anastrozole and letrozole. Two experts review the scientific evidence on these valuable agents. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation following the sole administration of gonadotrophin-releasing hormone agonists (GnRHa) is exceedingly rare. We hereby report on two infertile patients undergoing in-vitro fertilization-embryo transfer who developed ovarian hyperstimulation under such circumstances. In both patients, GnRHa were administered using the 'long protocol' regimen. The first patient developed ovarian hyperstimulation on two occasions, with mid-luteal depot administration of triptorelin and with early follicular triptorelin, administered as daily subcutaneous injections. In both cycles, within 2 weeks of triptorelin therapy, massive ovarian multifollicular enlargement occurred, concomitant with high serum oestradiol concentrations, which resolved spontaneously following expectant management. The second patient developed ovarian hyperstimulation following daily injections of leuprolide acetate starting at the mid-luteal phase. The final stage of ovulation was triggered by human chorionic gonadotrophin (HCG) and 11 oocytes were retrieved. In-vitro fertilization resulted in embryo formation, but failed to result in pregnancy. The same phenomenon recurred in a subsequent cycle despite preventive pretreatment with an oral contraceptive. A negative GnRH test, performed just before HCG administration, suggested than an ongoing 'flare-up effect' was unlikely to cause ovarian stimulation. Ovarian hyperstimulation can occur following the sole administration of GnRHa irrespective of the preparation used and the administration protocol. Although spontaneous resolution is the rule, once this condition has developed, HCG administration and oocyte retrieval are feasible. This rare entity probably represents an exaggerated form of ovarian cyst formation following GnRHa administration, the underlying pathophysiology of which remains unresolved. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of the generation of reactive oxygen species (ROS) on the integrity of the DNA of human spermatozoa, and to determine if pretreatment with antioxidants can reduce DNA damage. Samples were obtained from 47 men undergoing infertility investigation. ROS were generated in the samples by the addition of xanthine/xanthine oxidase (X/XO) with or without antioxidants. After incubation at timed intervals (0-2 h) with X/XO, the percentage of spermatozoa with DNA fragmentation was determined using the method of TdT-mediated DNA end-labelling (TUNEL). Time intervals were selected to mimic the clinical situation in which spermatozoa are held for a period of time after swim-up while the oocytes are prepared for ICSI. A significant increase in sperm DNA damage was evident when samples were incubated in the presence of ROS for intervals of 1 and 2 h, but not when incubated with ROS for <1 h (P = 0.0001). The addition of antioxidants significantly decreased the amount of DNA damage induced by ROS generation (P < 0.04). ROS can cause an increase in DNA fragmentation and pretreatment with antioxidants can reduce DNA damage. [ABSTRACT FROM PUBLISHER]

The objective of the present study was to assess the integrity of maternal and/or paternal chromatin in injected oocytes that remained unfertilized after intracytoplasmic sperm injection (ICSI). The study was performed on 102 oocytes that failed to show pronuclear formation 18-20 h after ICSI. We used chromatin labelling with 4,6-diamidino-2-phenylindole (DAPI) to identify maternal and paternal chromatin, coupled with biotin-mediated end-labelling to assess DNA fragmentation in each gamete. It was shown that 50% of oocytes without pronuclear formation following ICSI contained chromatin with damaged DNA, and that the source of the DNA fragmentation was equally divided between the spermatozoon (25.8%) and the oocyte (24.4%). A significantly greater proportion of condensed spermatozoa in human oocytes had damaged DNA, compared to decondensed spermatozoa (24.7 compared to 5.9%, P = 0.002). There was a significant increase in the incidence of DNA fragmentation in oocytes from patients older than 35 years (65 ± 1.2%) compared to those from younger patients (36 ± 1.0%) (P < 0.05). Further, 17% of unfertilized oocytes contained no paternal chromatin. Thus, DNA fragmentation in both spermatozoa and oocytes is associated with failure of fertilization in ICSI. In some cases of severe male factor infertility, a significant proportion of spermatozoa injected into oocytes may contain fragmented DNA. Injection of oocytes with spermatozoa containing abnormal chromatin will probably result in failure of sperm decondensation and fertilization. In older women, a significant proportion of oocytes injected may contain fragmented DNA. These observations may explain the consistent inability of most clinics to achieve fertilization rates higher than 65% with ICSI. [ABSTRACT FROM PUBLISHER]

Although clomiphene citrate and FSH remain the mainstay of therapy for ovarian stimulation among women with unexplained infertility, both drugs have their shortcomings. Two experts present the evidence supporting the value of AIs in this patient population. [ABSTRACT FROM AUTHOR]

Investigates the effect of maternal age and conditions of fertilization on programmed cell death during murine preimplantation embryo development. Reduction of the rate of blastocyst formation and decreased mean cell number at the blastocyst stage due to in vitro fertilization (IVF); Effect of IVF and maternal age on the cell death index.

Preimplantation genetic testing for aneuploidy (PGT-A) is a common add-on to IVF cycles. As it is presently performed, PGT-A relies on whole genome amplification of small amounts of DNA from cells removed from the trophectoderm (TE) of a blastocyst for determination of gain or loss of chromosomal material by next-generation sequencing. Whole genome amplification may introduce artifacts such as allele dropout and loss of heterozygosity in up to 25% of cases. In addition, the high prevalence of mosaicism in human embryos is a complicating factor in interpreting the results of PGT-A screening. In the presence of mosaicism, biopsy of TE cells cannot provide accurate results regarding the chromosomal make-up of the inner cell mass. The available clinical data suggest that PGT-A is probably harmful when IVF outcomes are analyzed by intention to treat or by live birth rate per cycle started rather than per embryo transfer, especially in women with three or fewer blastocysts. In addition, hypothesized advantages of reduced spontaneous abortion rate and reduced time to conception may be modest at best., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Research Question: Does a decrease in endometrial thickness (compaction ≥10%) before embryo transfer prognosticate the risk for preterm birth and placenta-mediated pregnancy complications among IVF pregnancies?, Design: Retrospective cohort study at a large private fertility practice. Patients with a singleton live birth after a fresh or frozen embryo transfer between 2016 and 2019 were included. The primary outcome was preterm birth (delivery before 37 weeks gestational age). Secondary outcomes included gestational hypertension, pre-eclampsia, intrauterine growth restriction and placental abruption., Results: Of the 252 patients that met the study criteria, 122 (48%) demonstrated endometrial compaction (≥10%) and 130 (52%) did not. Age, body mass index (BMI), parity, history of preterm birth or history of pre-existing maternal conditions between the compaction and no-compaction groups were not significantly different. The overall prevalence of placenta-mediated complications across all participants was 25% (n = 62). The number of preterm births between the compaction and no-compaction groups (13% and 6%, respectively, P = 0.09) as well as the prevalence of placenta-mediated complications (29.5% and 20%, respectively, P = 0.08) were not significantly different. Findings for the primary outcome (preterm birth) persisted even after adjustment for potential confounding variables, including maternal age, parity, BMI, embryo score and type of embryo transfer (fresh versus frozen) (adjusted OR 1.86, 95% CI 0.64 to 5.38)., Conclusions: Endometrial compaction (or decrease in endometrial thickness) before embryo transfer is not associated with preterm birth or placenta-mediated pregnancy complications., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This brief review will examine the investigation of the endometrial cavity before embryo transfer using various techniques, including hysteroscopy, endometrial biopsy using immunohistochemistry and molecular microarray, and ultrasound imaging. All these investigative tools are presently subject to controversy and require large prospective controlled trials for validation. During embryo transfer, the occurrence of a retained embryo does not appear to have a negative impact on pregnancy outcome, and finally, consistent data indicate that physical activity immediately after embryo transfer has no impact on pregnancy outcome., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to explore the utility of preimplantation genetic testing for aneuploidy (PGT-A) in a poor prognosis group of women with few embryos available for transfer., Methods: This was a retrospective matched cohort study examining records for first or second-cycle IVF patients with 1 to 3 blastocysts. The study group comprised 130 patients who underwent PGT-A on all embryos. The control group included 130 patients matched by age, BMI, and blastocyst number and quality who did not undergo PGT-A during the same time period., Results: The live birth rate (LBR) per embryo transfer (ET) were similar in the PGT-A and control groups, and the spontaneous abortion (SAB) rate was the same (23%). However, we found a significantly higher LBR per oocyte retrieval in the control group vs the PGT-A group (43% vs 20%, respectively) likely due to the many no-euploid cycles in the PGT-A group. In a subgroup analysis for age, the similar LBR per ET persisted in women < 38. However, in older women, there was a trend to a higher LBR per ET in the PGT-A group (43%) vs the control group (22%) but a higher LBR per oocyte retrieval in the control group (31%) vs the PGT-A group (13%)., Conclusions: Overall, we observed a significant increase in LBR per oocyte retrieval in women in the control group compared to women undergoing PGT-A, and no difference in SAB rate. Our data suggests that PGT-A has no benefit in a subpopulation of women with few embryos and may cause harm., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To evaluates the effect of different modes of final follicular maturation triggering on the degree of apoptosis of granulosa cells (GCs) and the potential effect on progesterone secretion., Methods: Thirty patients undergoing controlled ovarian hyperstimulation for IVF who received hCG, GnRH agonist, or dual trigger for final follicular maturation were included in the study. Granulosa cells were obtained at the time of oocyte retrieval. The proportion of apoptotic cells was evaluated via TUNEL and immunohistochemistry., Results: The proportion of apoptotic cells was significantly higher in the GnRH agonist-alone group compared to hCG-alone and the dual trigger groups (13.5 ± 1.5% vs. 7.8% ± 1.8 vs. 10.1% ± 2, respectively, P < 0.01). Moreover, the expression of active-caspase-3 was also significantly increased in the GnRH agonist-alone group compared with the hCG-alone and the dual trigger groups (15.5% ± 2.9 vs. 8.4% ± 1.6 vs. 12.7% ± 2.6, respectively, P < 0.01). The progesterone levels measured in the granulosa-luteal cell culture medium after 24 h of incubation were similar between the three groups., Conclusions: The levels of apoptosis are increased after GnRH agonist/dual trigger. The increased apoptosis might be one of the culprit of the subsequent premature demise of the corpus luteum post GnRH agonist trigger., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With the recent increased utilization of oocyte vitrification for the purpose of fertility preservation, information regarding the future fertility potential of the frozen oocytes is mandatory. Nowadays, there is a relative lack of data about prediction of assisted reproductive technique (ART) success relying on the retrieved oocytes. In the present study, we therefore aimed to investigate whether oocyte diameter might predict the quality of the developing embryo. A retrospective, single-center cohort study. Oocytes retrieved following controlled ovarian hyperstimulation cycles during 2016 and incubated in a time-lapse incubator system were analyzed. Oocytes were grouped by mean oocyte diameter (MOD) and incubated for 5 days before the final morphological evaluation done by an expert embryologist. A total of 471 cycles which yielded 3355 metaphase II oocytes were included in the analysis. Embryos developed from oocytes with MOD close to the average (Average 1SD < MOD < Average + 1SD) had increased good-quality blastulation rates compared with embryos that developed from very small or very large oocytes. Oocytes with MOD between 105.96 and 118.69 μm have better probability of becoming top-quality D5 blastocysts (17.1-17.4% grade 1 embryos). There is a correlation between oocyte's MOD and the embryo quality at day 5. The oocytes with near average MOD have a better chance to develop to a good-quality embryo. Therefore, the study suggests that MOD might serve as a predictor for embryo grading at day 5.

Background: To explore the efficacy of follitropin delta in ovarian stimulation of patients with the Rotterdam ESHRE/ASRM 2003 phenotypes of polycystic ovarian syndrome (PCOS) using a retrospective case series with an electronic file search in a reproductive medicine clinic., Case Presentation: Seventy-four patients with PCOS undergoing ovarian stimulation according to the individualized dosing algorithm of follitropin delta for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)/oocyte freezing were included. Follitropin delta resulted in a high number of pre-ovulatory follicles at the end of stimulation as expected in patients with PCOS. There was a large number of oocytes retrieved with an acceptable percentage of metaphase II (MII) oocytes. There were no cases of moderate or severe OHSS across all phenotypes., Conclusion: Follitropin delta, using the individualized dosing algorithm, appears to be a safe method of ovarian stimulation with a low risk of OHSS in PCOS patients without sacrificing successful stimulation outcomes.

Study Question: Does co-administration of GnRH agonist and Human chorionic gonadotropin (hCG; dual trigger) in IVF cycles improve the number of mature oocytes and pregnancy outcome compared to hCG alone?, Summary Answer: Using the dual trigger for final follicular maturation increases the number of oocytes, mature oocytes and number of blastocysts (total and top-quality) compared to triggering with hCG alone., What Is Known Already: hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates., Study Design, Size, Duration: A single center, randomized controlled, double-blinded clinical trial between May 2016 and June 2018 analyzed by intention to treat (ITT)., Participants/materials, Settings, Methods: One hundred and fifty-five normal responder patients were randomized either to receive hCG or dual trigger for final oocyte maturation. Data on patients age, BMI, AMH, number of oocytes retrieved, number of metaphase 2 (MII) oocytes, zygotes and blastocysts, clinical pregnancy rate and live birth rate were assessed and compared between the dual trigger group and the hCG group. We performed a planned interim analysis after the recruitment of 50% of the patients. Based on the totality of outcomes at the interim analysis we decided to discontinue further recruitment., Main Results and the Role of Chance: One hundred and fifty-five patients were included in the study. The age (36 years versus 35.3 years P = NS), BMI (24 kg/m2 versus 23.7 kg/m2) and the AMH (20.1 pmol/l versus 22.4 pmol/l) were comparable between the two groups. Based on ITT analysis, the number of eggs retrieved (11.1 versus 13.4, P = 0.002), the MII oocytes (8.6 versus 10.3, P = 0.009), total number of blastocysts (2.9 versus 3.9, P = 0.01) and top-quality blastocysts transferred (44.7% versus 64.9%; P = 0.003) were significantly higher in the dual trigger group compared to the hCG group. The clinical pregnancy rate (24.3% versus 46.1%, OR 2.65 (1.43-1.93), P = 0.009) and the live birth rate per transfer (22% versus 36.2%, OR= 1.98 (1.05-3.75), P = 0.03) were significantly higher in the dual trigger group compared to the hCG group., Limitations, Reasons for Caution: None., Wider Implications of the Findings: The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely., Study Funding/competing Interest(s): The study was funded by TRIO Fertility. There are no conflicts of interest to declare., Trial Registration Number: ClinicalTrials.gov identifier: NCT02703584., Date of Trial Registration: March 2016., Date of First Patient's Enrollment: May 2016., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs)., Design: An observational cohort study., Setting: Single tertiary care medical center., Patient(s): Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post-preimplantation genetic testing for aneuploidy (PGT-A)., Intervention(s): Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET., Main Outcome Measure(s): Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET., Result(s): We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact., Conclusion(s): There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endometrial receptivity appears to be as important as chromosomal normality in determining embryo implantation and pregnancy outcome, because the ongoing pregnancy rate with transfer of preimplantation genetic testing for aneuploidy euploid blastocysts is ∼50%. This Views and Reviews article focuses on our current knowledge of the biology of endometrial receptivity and on the role of both invasive (endometrial biopsy) and noninvasive (ultrasound) assessment in successful endometrial preparation for frozen-thawed embryo transfer., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Visible light is the principal stimulus for resetting the mammalian central circadian pacemaker. Circadian phase resetting is most sensitive to short-wavelength (blue) visible light. We examined the effects of removing short-wavelengths < 500 nm from polychromatic white light using optical filters on circadian phase resetting in rats. Under high irradiance conditions, both long- (7 h) and short- (1 h) duration short-wavelength filtered (< 500 nm) light exposure attenuated phase-delay shifts in locomotor activity rhythms by (∼40-50%) as compared to unfiltered light exposure. However, there was no attenuation in phase resetting under low irradiance conditions. Additionally, the reduction in phase-delay shifts corresponded to regionally specific attenuation in molecular markers of pacemaker activation in response to light exposure, including c-FOS, Per1 and Per2. These results demonstrate that removing short-wavelengths from polychromatic white light can attenuate circadian phase resetting in an irradiance dependent manner. These results have important implications for designing and optimizing lighting interventions to enhance circadian adaptation.

Objective: To evaluate whether the change in endometrial thickness between the end of the estrogen phase and the day of embryo transfer has an impact on the pregnancy rate in frozen-thawed embryo transfer (FET) cycles., Design: Retrospective observational cohort study., Setting: Single tertiary care medical center., Patient(s): Ultrasound images in 274 FET cycles were reviewed. All patients underwent endometrial preparation with the use of hormonal therapy., Interventions(s): Ultrasound measurements of endometrial thickness at the end of the estrogen phase and the day of embryo transfer., Main Outcome Measure(s): The change in endometrial thickness and ongoing pregnancy rate., Result(s): We calculated the ongoing pregnancy rate in patients whose endometrial thickness decreased (compacted) after starting progesterone by 5%, 10%, 15%, or 20% compared with patients with no change or increased endometrial thickness. The ongoing pregnancy rate was significantly increased at all levels of compaction compared with no compaction. The ongoing pregnancy rate showed a significant increase with each decreasing quartile of change in thickness (increased percentage of compaction) in the progesterone phase compared with the estrogen phase., Conclusion(s): There is a highly significant inverse correlation between the ongoing pregnancy rate and the change of endometrial thickness between the end of estrogen administration and the day of embryo transfer., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Today, most IVF programs have moved to blastocyst transfer but there is still uncertainty regarding when to transfer if there are only one or two embryos at the cleavage stage. The aim of this study was to compare the pregnancy rate of day 3 transfers vs. blastocyst stage transfers in patients who had only one or two embryos on day 3. We conducted a retrospective study of 102 patients with one or two cleavage stage embryos that had their embryos transferred on day 3 and 429 patients had their embryos cultured to day 5 for transfer. The number of mature oocytes (4.0 vs 4.6, p  = NS) and number of cleavage stage embryos on day 3 was similar in the two groups (1.3 vs. 1.5, p =  NS). The clinical pregnancy rate per retrieval (22% vs. 24.6%, p=  NS) and the ongoing pregnancy rate per retrieval (20% vs. 20.2%, p =  NS) was comparable between the groups. Fifty seven (13.2%) of the patients had cleavage embryo arrest and did not have an embryo to transfer on day 5. We conclude that the cumulative pregnancy rate is the same for patients with 1-2 cleavage stage embryos regardless of whether the embryo is transferred on day 3 or day 5.

Over the past four decades, due to cultural and social changes, women in the developed world have significantly delayed childbirth. This trend is even worse for patients who attend infertility clinics. It is well-known that live birth rates in women older than 35 are significantly lower than in those younger, both naturally and with assisted reproduction. Fertility decline is, in part, due to an increase in oocyte aneuploidy that leads to a reduced embryo quality, as well as an increased incidence of miscarriages and birth defects. Here we show that aging-associated malfunction is not restricted to the oocyte, as cumulus granulosa cells also display a series of defects linked to mitochondrial activity. In, both, human and mouse model, a decline in cumulus cell function due to increased maternal age is accompanied by a decreased expression of enzymes responsible for Coenzyme Q (CoQ) production, particularly Pdss2 and CoQ6. In an aged mouse model supplementation with Coenzyme Q10-a potent stimulator of mitochondrial function-restored cumulus cell number, stimulated glucose uptake, and increased progesterone production. CoQ10 supplementation might, thus, improve oocyte and cumulus cells quantity and quality, by improving the mitochondrial metabolism in females of advanced maternal age.

Purpose: Recent studies have focused on transvaginal ultrasound measurement (TVUS) of sub-endometrial contractility and computer-enhanced 3-D modeling scoring of the endometrium prior to embryo transfer (ET).The aim of this study was to compare pregnancy outcome of patients who performed the 3-D scoring or the sub-endometrial measurement prior to the ET with patients that did not perform those procedures., Methods: A single center retrospective cohort study of 635 freeze/thaw cycles of blastocysts vitrified on day 5 and transferred between January 2016 and August 2016., Results: We compared the patients who performed 3-D scoring with the control group and found comparable patients' characteristics, clinical pregnancy rates (42% vs. 44.3, p = NS, respectively), and ongoing pregnancy rates (31.7% vs. 33.9%, p = NS).We then compared the patients who performed the sub-endometrial wave measurements with the control group and found similar findings. The clinical pregnancy rate (38.2% vs. 44.3, p = NS, respectively) and the ongoing pregnancy rate (30.8% vs. 33.9%) were comparable between the two groups. We performed a regression analysis to examine the independent contribution of different variables to the ongoing pregnancy rates. Both the 3-D and the wave count procedures were not found to have any influence on the ongoing pregnancy rates., Conclusions: Although new ultrasonic methods of evaluating the endometrium have been proposed during the last years, these methods have not been shown to improve the pregnancy rates compared to the original method of assessing the endometrium by measuring the endometrial thickness.

Objective: To describe and compare the ongoing pregnancy rate between morulae and cavitating morulae (CAVM) transferred on day 5, to describe and compare the blastulation rate between day 5 morulae and CAVM, and to describe the pregnancy rate of these slow-developing blastocysts during a frozen embryo transfer (FET) cycle., Design: Retrospective cohort study., Setting: Single tertiary care medical center., Patient(s): Delayed-development embryos: 3,321 cycles that included 10,304 embryos on day 5 that were cultured until day 6., Intervention(s): Development of morula and CAVM to the blastocyst stage., Main Outcome Measure(s): Blastulation rate., Result(s): The fresh embryo transfers comprised 186 patients with 82 embryos at the morula stage and 104 embryos at the CAVM stage. The pregnancy rate (15.8% vs. 21.1%) and the ongoing pregnancy rate (15.8% vs. 17.3%) were comparable between the groups. The study group included 10,304 day-5 delayed embryos: 5,395 morulae and 4,909 CAVM on day 5. The blastulation rate was statistically significantly higher in the CAVM group compared with the morula group (39.2% vs. 20.4%). We included 201 FET cycles: 77 warmed blastocysts that developed from a morula on day 5 and 124 warmed blastocysts that developed from CAVM on day 5. The clinical pregnancy rate was comparable between the two groups per embryo transfer (21.3% vs. 24.7%)., Conclusion(s): Transferring of fresh, slow-developing embryos seems to improve the cycle outcomes compared with culturing for another day and then vitrifying and thawing later., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: A few years ago, we started to use a new freeze-thaw protocol for the frozen embryo transfer cycles. Instead of thawing the embryos 2-4 h prior to the transfer, we started thawing the embryos 20-22 h prior to the transfer. The aim of this study was to compare the pregnancy rate in cases of embryos that continued to develop in the post-thawing culture to that of embryos that did not., Methods: A retrospective cohort study of blastocyst freeze/thaw cycles vitrified on day 5, thawed and transferred after 20-22 h in the culture, between January 2012 and December 2016., Results: A total of 375 patients were included in the analysis. Two hundred twenty-eight embryos graded as good, 87 graded as fair, and 60 graded as poor embryos were transferred. The clinical pregnancy rate (50% vs. 19.5% vs 3.3% p < 0.01) and the ongoing pregnancy rate (38.5% vs. 13.6% vs 1.7% p < 0.01) were higher in cases of good embryo quality compared with fair and poor-quality embryos, respectively. For good embryos, progressing to a better grade during the culture did not change the clinical pregnancy rate (51.3% vs. 46.2% p = NS) or the ongoing pregnancy rate (38.5% vs. 37.5% p = NS). For fair embryos, progressing to a better grade during the culture resulted in a higher clinical pregnancy rate (25.4% vs 9% p = 0.05)., Conclusions: The development of the fair embryos in the culture has a highly positive impact on the pregnancy rate and this factor should be taken into consideration before deciding how many embryos to transfer.

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Many Patients with persistent retained products of conception prefers to avoid surgical interventions, such as a dilatation and curettage (D&C) that might pose an additional future risk to their already compromised fertility or obstetric performance. The aim of this study was to the possibility of induced withdrawal bleeding following oral contraceptive administration as a non-surgical treatment for patients with persistent retained products of conception (RPOC). A retrospective study of patients presenting with retained products of conception (RPOC) after failed expectant management or after treatment with PGE1 was performed. Twelve women presenting with RPOC at ≤8 weeks gestation with minimal to mild vaginal bleeding and no signs of infection were treated with oral contraceptive pill (OCP) containing 0.03 mg ethinylestradiol and 0.15 mg of desogestrel for 3 weeks. Out of the 12 patients treated, nine women (75%) successfully expelled the RPOC after completing the three-week course of OCPs. The three cases (25%) that did not resolve following OCP treatment had pregnancy products with positive blood flow on Doppler examination. We conclude that OCPs may be a useful medical treatment option for persisting RPOC in selected patients with absence blood flow on Doppler examination wishing to avoid surgical intervention.

Background: Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation. The aim of this study was to compare the VEGF and PEDF levels in the follicular fluids of normal responders treated with letrozole and gonadotropins during the ovarian stimulation with patients treated with gonadotropins only., Methods: A single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits., Results: The age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209 nmol/l vs. 3280 nmol/l, p = 0.02) were significantly decreased, and the testosterone levels (246.5 nmol/l vs. 40.7 nmol/l, p < 0.001) were significantly increased in the letrozole group compared to the gonadotropin only group. The progesterone levels (21.4 μmol/l vs. 17.5 p = NS) were comparable between the two groups. The VEGF levels (2992 pg/ml vs. 1812 pg/ml p = 0.02) were significantly increased and the PEDF levels (9.7 ng/ml vs 17.3 ng/ml p < 0.001) were significantly decreased in the letrozole group., Conclusions: Opposite to observations in the mouse, we found that VEGF levels were increased and PEDF levels were decreased in the follicular fluid in patients treated with letrozole during the stimulation cycles. Further investigation is required to determine if patients treated with letrozole during the IVF stimulation protocol are at increased risk for developing OHSS as a result of these findings.