Embryos derived from single pronucleus are suitable for preimplantation genetic testing.

OBJECTIVE: To study and compare the preimplantation genetic testing for monogenic disorders (PGT-M) results, and to evaluate the treatment cycle outcomes of embryos derived from a single pronucleus (1PN) vs. two pronuclei (2PN). DESIGN: A retrospective cohort study from January 2018 to December 2022 involving in vitro fertilization (IVF)-PGT-M treatment cycles. SETTING: Single, academically affiliated fertility center. PATIENTS: A total of 244 patients underwent 351 IVF-PGT-M treatment cycles. INTERVENTION: Embryo biopsy with molecular testing for a monogenic disorder. MAIN OUTCOME MEASURES: The molecular diagnosis results and clinical outcomes after the transfer of embryos derived from 1PN and 2PN in IVF-PGT-M treatment cycles. RESULTS: Embryos derived from 1PN have a significantly low developmental potential with a lower rate of embryos that underwent biopsy compared with 2PN-derived embryos; 1PN-derived embryos demonstrated a significantly lower number of blastocysts (24% vs. 37.9%) and top-quality blastocysts (22.3% vs. 48.1%) compared with 2PN-derived embryos. Lower successfully completed and unaffected PGT-M results were achieved in 1PN compared with 2PN-derived embryos (47.1% vs. 65.5% and 18.7% vs. 31.6%, respectively), with significantly higher abnormal molecular results (39.6% vs. 22.7%). The embryo transfer of 24 1PN-derived embryos with no affected genetic disorder resulted in 5 (20.8%) clinical pregnancies and 4 (16.7%) live births (LBs). CONCLUSIONS: Within the limits of fewer embryos derived from 1PN that yielded unaffected embryos suitable for transfer, the clinical pregnancy and LB rate of 1PN embryos undergoing PGT-M are reassuring. We, therefore, suggest applying PGT-M to embryos derived from 1PN embryos to improve the cumulative clinical pregnancy and LB rates.

Predicting IVF outcome in poor ovarian responders.

BACKGROUND: Poor responders to ovarian stimulation are one of the most challenging populations to treat. As a failed cycle can cause a considerable emotional and economical loss, adequate fertility counseling addressing patients' expectations are highly important when facing patients with poor ovarian response. The study aimed to evaluate reproductive outcomes and to identify factors associated with live birth (LB) after fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles of patients fulfilling the Bologna criteria for poor ovarian response (POR). METHODS: A retrospective study included 751 IVF/ICSI treatment cycles which yielded up to three retrieved oocytes, at a tertiary referral hospital between January 2016 and February 2020. A logistic regression analysis was used to adjust for confounders. RESULTS: Clinical pregnancy and LB rate per cycle were significantly higher among women younger versus older than 40 years (9.8% and 6.8% vs 4.5% and 2.1%, p < 0.01, respectively). Patients who achieved LB were significantly younger, had higher number of oocytes retrieved, fertilization rate and top-quality embryos (p < 0.05). Multivariable regression analysis identified patient's age (OR 0.90; 95% CI 0.845-0.97; p = 0.005) and mean number retrieved oocytes (OR 1.95; 95% CI 1.20-3.16; p = 0.007) as factors significantly associated with the probability of a LB. CONCLUSIONS: The woman's age and the number of retrieved oocytes are both independent predicting factors of live birth in poor ovarian responders. Considering the risks, the high financial investment and poor reproductive outcomes involved in IVF treatments, raises questions regarding the adequacy of providing treatments in these patients' population. POR younger than 40 years may represent a possible exception due to acceptable probability for a LB.

The association between level of physical activity and pregnancy rate after embryo transfer: a prospective study.

RESEARCH QUESTION: Is physical activity after embryo transfer, as assessed by a smart band activity tracker, associated with decreased pregnancy rates? DESIGN: Prospective observational cohort study comprising infertile women aged < 38 years, who had undergone fewer than three previous embryo transfers, achieved a good ovarian response and were undergoing frozen-thawed embryo transfer in a tertiary-referral centre. A validated smart band activity tracker was used to assess physical activity level immediately after the embryo transfer and until the pregnancy test. No specific recommendations were given to participants on level or intensity of physical activity. Physicians and patients were blinded to the data stored in the pedometer. Primary outcome was ongoing pregnancy rate. RESULTS: Fifty women met the inclusion criteria. Ongoing pregnancy rate was 30%. In a pooled analysis, participants walked significantly fewer steps per day on the day of embryo transfer compared with the first 2 days after embryo transfer (4075, interquatile range [IQR] 2932-5592 versus 5204, IQR4203-8584, P = 0.01). No significant difference was observed between pregnant women and non-pregnant women in the median steps per day after embryo transfer until serum beta-HCG was measured (7569, IQR 6008-10884 versus 6572.5, IQR 5299-8786, P = 0.43). No significant difference was observed in the median number of steps on the day of embryo transfer or the first 2 days after embryo transfer between pregnant and non-pregnant women. CONCLUSIONS: A quantitative objective assessment of the association between physical activity and pregnancy rates after frozen-thawed embryo transfer was conducted. Ambulation after embryo transfer has no adverse effect on pregnancy rates and, therefore, women should resume regular activity immediately after embryo transfer.

Cleavage vs blastocyst stage embryos: how are they interrelating?

PURPOSE: To assess the variables that may predict which cleavage-stage embryo may develop into a blastocyst, and vice versa, to determine whether the cleavage-stage embryo morphology should be taken into consideration when transferring the embryo at the blastocyst stage. METHODS: A single center, retrospective cohort study. The study cohort included 3072 patients undergoing 3607 retrieval cycles and 23,124 embryos at the cleavage stage. We assessed the blastulation rate and evaluated which variables impact the ongoing pregnancy rate. RESULTS: High blastulation rate correlates with higher embryos' grading (I > II > III > IV > V) and higher number of blastomeres (8 > 7 > 6 > 5 > 4). 949 patients had fresh single blastocyst transfers. The ongoing pregnancy rate was 28.9% per transfer. Patients with ongoing pregnancies were significantly younger (34.3 vs. 36 years, p < 0.001), had higher number of oocyte yield (9.8 vs. 9, p = 0.02), and an increased rate of good-quality embryos transferred (70.7% vs. 47.7%, p = 0.001). When evaluating embryos progression, we found that whenever embryo developed to a good-quality blastocyst, its appearance at the cleavage stage did not affect ongoing pregnancy rate. CONCLUSION: Higher the number of blastomeres and better embryo grading were found to correlate with a higher blastulation rate. Nevertheless, if the embryo has already developed to a top-quality blastocyst, its morphology at the cleavage stage did not impact ongoing pregnancy rate.

Can Oocyte Diameter Predict Embryo Quality?

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.

The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the role of intracytoplasmic sperm injection (ICSI) in the treatment of non-male factor infertile patients aged ≥ 39. METHODS: This is a single-center, prospective, randomized controlled clinical trial, between March 2018 and December 2019. Sixty-nine patients were recruited, and sixty patients participated in the study. Their ovaries were randomized prior to the beginning of the ovarian stimulation: the oocytes from one side (n = 257) were allocated to the ICSI (ICSI arm), while those of the contralateral side (n = 258) were allocated to conventional insemination (IVF arm). The fertilization rate per oocyte retrieved, number of zygotes (2PN), and cleavage-stage embryos were assessed and compared between the two study groups. RESULTS: The average number of zygotes (3.1 vs. 2.7 p = 0.45), the fertilization rate (72.4% vs. 65.1% p = 0.38), the average number of cleavage-stage (2.8 vs. 2.4 p = 0.29), and the average top-quality embryos (TQE) cleavage-stage embryos (1.7 vs. 1.6 p = 0.94) were comparable between the two groups. The TQE rate per randomized oocyte (41.2% vs. 41% p = 0.8) was also similar in both groups. CONCLUSIONS: ICSI does not improve the reproductive outcomes of advanced-age patients undergoing conventional insemination for non-male factor infertility. TRIAL REGISTRATION: NCT03370068.

Stop GnRH-Agonist Combined With Multiple-Dose GnRH-Antagonist Protocol for Patients With "Genuine" Poor Response Undergoing Controlled Ovarian Hyperstimulation for IVF.

Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients. Design: Cohort historical, proof of concept study. Setting: Tertiary, University affiliated Medical Center. Patient(s): Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only "genuine" poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU. Main Outcome Measure(s): Number of oocytes retrieved, number of top-quality embryos, COH variables. Result(s): The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation. Conclusion(s): The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating "genuine" poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept.

AIM: The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase. PATIENTS AND METHODS: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle. RESULTS: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%). CONCLUSIONS: The combined Stop GnRH-ag/GnRH-ant OS protocol is a valuable tool in the armamentarium for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients' subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Endometrial compaction before frozen euploid embryo transfer improves ongoing pregnancy rates.

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.

Can we predict oocyte maturation prior to denudation for intracytoplasmic sperm injection?

Intracytoplasmic sperm injection (ICSI) was introduced in 1992 as a method to treat couples with severe male infertility. However, in the last two decades, the use of ICSI has increased substantially even among patients without male factor infertility. In ICSI the oocytes are scrutinized for maturity upon insemination and the immature oocytes are discarded. The aim of the present study was to assess the ability of an experienced embryologist to identify the maturity of the oocytes prior to their denudation.In the present prospective observational study, four experienced embryologists examined the oocytes prior to their denudation and decided whether the oocytes were mature or immature. Later, the oocytes were denudated and the embryologist again examined the oocytes to confirm their prior assumptions.483 oocytes were examined by four embryologists. Three hundred and fifty one of the oocytes were mature (72.7%) and 132 were immature (27.3%). The embryologists were able to correctly identify oocytes maturation status in 85.3% of cases. The embryologists were able to correctly identify 90% of the mature oocytes and 72.7% of the immature oocytes. When they assumed that the oocytes were mature they were correct in 89.% of the cases, while only 74.6% of their prediction that the oocytes were immature were true. To conclude, the embryologists are able to identify the oocytes maturation status before denudation at the majority of the cases. Whenever the oocytes are suspected to be immature, further consideration should be made whether to proceed to ICSI or not.

Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers.

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.

Does double trigger (GnRH-agonist + hCG) improve outcome in poor responders undergoing IVF-ET cycle? A pilot study.

Many strategies are offered for the treatment of poor responders. However, no compelling advantage for one stimulation protocol over another has been hitherto established. In this study, we aimed to evaluate the role of different modes and timings of final follicular maturation trigger, on in vitro fertilization (IVF) cycle outcome of poor responder patients. In the present randomized controlled study, poor responder patients, according to the Bologna criteria, undergoing controlled ovarian hyperstimulation (COH) using the gonadotropin-releasing hormone (GnRH) antagonist protocol were randomly assigned to three different final follicular maturation trigger modes and timings: hCG 36 h before oocyte pick-up (OPU) (hCG trigger); GnRH agonist (GnRHag) 36 h before (OPU) and hCG on day of OPU (GnRHag trigger); and GnRHag and hCG, 40 and 34 h prior to OPU, respectively (double trigger). Pregnancy rate, number of oocytes, and top quality embryos (TQEs). Thirty-three poor responder patients were recruited and randomized to the different study groups. While there were no in-between groups' differences in patients' demographics and stimulation variables, patients in the double trigger group had a significantly higher number of TQE (1.1 ± 0.9 vs. 0.3 ± 0.8 and 0.5 + 0.7; p<.02) as compared to the hCG trigger and the GnRH-ag trigger groups, respectively, with an acceptable pregnancy rate. Double trigger offers an additional benefit to poor responder patients. Larger studies are required to support this new concept prior to its implementation to IVF practice.

Developmental potential of slow-developing embryos: day-5 morulae compared with day-5 cavitating morulae.

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.

Influence of seasonal variation on in vitro fertilization success.

OBJECTIVE: To evaluate the influence of seasonal variation on in vitro fertilization (IVF) outcome in a large cohort population. METHODS & MATERIALS: A total of 5,765 IVF cycles conducted in Sheba medical center between 2013 and 2016 were retrospectively analyzed. The treatment cycles included 4214 ovarian stimulation and ovum pick up (OPU) cycles of which 3020 resulted in fresh embryo transfer and 1551 vitrified- warmed cycles of which1400 resulted in warmed embryo transfer. Cycles were assigned to seasons according to the date of OPU for fresh embryo transfer cycles or according to the date of embryo warming for vitrified warmed embryo transfer cycles. RESULTS: There were no statistically significant differences between the calendar months or seasons concerning the number of oocytes retrieved or fertilization rate in the fresh cycles. Throughout the 4 years of the study, the monthly clinical pregnancy rate fluctuated between 18.2% and 27.9% per fresh embryo transfer (mean 23.3%) and between 17.7% and 29.4% per vitrified warmed embryo transfer (mean 23%). These fluctuations did not follow any specific seasonal pattern. CONCLUSIONS: Our study did not demonstrate any significant influence of the calendar months or seasons on the clinical pregnancy rates of fresh or vitrified warmed embryo transfers. It might be speculated that the complete pharmaceutical control of the ovarian and endometrial function, as well as the homogeneous treatments, procedures and laboratory equipment used during the study period have lowered the influence of seasonal effect on IVF treatment outcome.

A novel approach to infertility treatment of advance-age patient with prominent intramural fibroid.

We report for the first time on a case of infertile advance-age patient with large intramural fibroid, who conceived following a course of Ulipristal. The patient underwent two fresh fertility preserving IVF cycles, with cryopreservation of 9 day-3 embryos, followed by a 12 weeks course of Ulipristal (5 mg per day) and a subsequent frozen-thawed embryo transfer with her own previously cryopreserved embryos. We, therefore, believe that Ulipristal is a valuable addition to treatment armamentarium of advance-age infertile patient with prominent intramural fibroid.

Is the oocyte quality affected by endometriosis? A review of the literature.

Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period causing infertility and pelvic pain. The disease, especially at the ovarian site has been shown to have a detrimental impact on ovarian physiology. Indeed, sonographic and histologic data tend to support the idea that ovarian follicles of endometriosis patients are decreased in number and more atretic. Moreover, the local intrafollicular environment of patients affected is characterized by alterations of the granulosa cell compartment including reduced P450 aromatase expression and increased intracellular reactive oxygen species generation. However, no comprehensive evaluation of the literature addressing the effect of endometriosis on oocyte quality from both a clinical and a biological perspective has so far been conducted. Based on this systematic review of the literature, oocytes retrieved from women affected by endometriosis are more likely to fail in vitro maturation and to show altered morphology and lower cytoplasmic mitochondrial content compared to women with other causes of infertility. Results from meta-analyses addressing IVF outcomes in women affected would indicate that a reduction in the number of mature oocytes retrieved is associated with endometriosis while a reduction in fertilization rates is more likely to be associated with minimal/mild rather than with moderate/severe disease. However, evidence in this field is still far to be conclusive, especially with regards to the effects of different stages of the disease and to the impact of patients' previous medical/surgical treatment(s).

Natural cycle frozen-thawed embryo transfer-can we improve cycle outcome?

PURPOSE: Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. In the present study, we aim to evaluate the outcome of natural cycle FET with modified luteal support. METHODS: All consecutive patients undergoing natural or artificial hormone replacement (AHR) day-2/3 FET cycles between May 2012 and June 2015 in our IVF unit were evaluated. While AHR FET cycles were consistent, those undergoing natural cycle FET received progesterone luteal support, and from June 2014, patients received two additional injections, one of recombinant hCG and the other of GnRH-agonist, on day of transfer and 4 days later, respectively (modified luteal support). RESULTS: Patients' clinical characteristics and laboratory/embryological variables were comparable between those undergoing natural vs. AHR cycles, during the earlier as compared to the later period. Moreover, while implantation, clinical, and ongoing pregnancy rates were significantly higher during the later period in patients undergoing the natural cycle FET with the modified luteal support (31, 51, and 46 %, respectively), as compared to natural (17, 26, and 20 %, respectively), or AHR FET in the late study period (15, 22, and 17 %, respectively), the natural cycle FET without the additional two injections yielded the same results, as the AHR cycles. CONCLUSIONS: We therefore suggest that in ovulatory patients undergoing FET, natural cycle FET with the modified luteal support should be the preparation protocol of choice. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

[Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].

OBJECTIVE: We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome. PATIENTS AND METHODS: All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose. RESULTS: Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate. CONCLUSIONS: In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

Combined effect of fetal sex and advanced maternal age on pregnancy outcomes.

BACKGROUND: Fetal sex and maternal age are each known to affect outcomes of pregnancies. The objective of the present study was to investigate the influence of the combination of maternal age and fetal sex on pregnancy outcomes in term and post-term singleton pregnancies. MATERIAL AND METHODS: This was a retrospective study on term singleton pregnancies delivered between 2004 and 2008 at the Chaim Sheba Medical Center. Data collected included maternal age, fetal sex, and maternal and neonatal complications. The combined effect of fetal sex and maternal age on complications of pregnancy was assessed by multivariable logistic regression models. RESULTS: The study population comprised 37,327 pregnancies. The risk of operative deliveries increased with maternal age ≥ 40 and in pregnancies with male fetuses. The risk of maternal diabetes and of longer hospitalization increased as maternal age increased, and in women ≥ 40 carrying male fetuses. The risk of hypertensive disorders increased in pregnancies with males as maternal age advanced. The risk of shoulder dystocia and neonatal respiratory complications increased in male neonates born to women<40. The risk of neonatal hypoglycemia increased in males for all maternal ages. CONCLUSIONS: Risk assessment for fetal sex and advanced maternal age were given for different pregnancy complications. Knowledge of fetal sex adds value to the risk assessment of pregnancies as maternal age increases.