Low Oocyte Yield Research Articles

A Higher Estradiol Rise After Dual Trigger in Progestin-Primed Ovarian Stimulation Is Associated With a Lower Oocyte and Mature Oocyte Yield in Normal Responders.

Background: Prior studies have shown that patients with a >10% estradiol (E2) rise after trigger had more oocytes retrieved than plateauing or decreasing E2 responders. However, multiple follicles develop at different stages of maturation during controlled ovarian stimulation (COS) and may exhibit different responses to trigger. The association between the magnitude of E2 increase and oocyte retrieval outcomes is still unclear.Methods: This was a retrospective cohort study of 2,898 women undergoing their first COS cycles with normal response from January 2014 to December 2017 at a tertiary-care academic medical center. Patients were categorized into five groups according to the percentage increase in E2 levels before and after dual trigger: <10.0%, 10.0–19.9%, 20.0–29.9%, 30.0–39.9%, and ≥40.0%. Univariable and multivariable linear regression analysis were performed to explore the association between E2 increase and oocyte/mature oocyte yield, while logistic regression was used to assess its effect on low oocyte/mature oocyte yield (<10th percentile).Results: The post-trigger E2 increase was negatively associated with both oocyte yield (P-trend < 0.001, adjusted P-trend = 0.033) and mature oocyte yield (P-trend < 0.001, adjusted P-trend = 0.002). Compared with a <10.0% E2 increase after trigger, patients with a ≥40.0% rise had fewer mature oocyte yield [adjusted mean absolute difference [MD] = −5.2, 95% confidence interval [CI]: −8.2–−1.8] and higher risk of low mature oocyte yield (adjusted odds ratio [OR] = 1.64, 95% CI: 1.04–2.60), whereas no statistical significance was found in oocyte yield (adjusted MD = −2.7, 95% CI: −6.1–0.8) and low oocyte yield (adjusted OR = 1.48, 95% CI: 0.96–2.28). In addition, the rates of implantation, positive pregnancy test, clinical pregnancy, ongoing pregnancy, pregnancy loss, and live birth were comparable among the 1,942 frozen embryo transfer cycles with embryos originating from different groups of E2 increase (all P > 0.05).Conclusions: A higher E2 rise after dual trigger is independently associated with a lower oocyte and mature oocyte yield in normal responders. Further studies are needed to explore the efficacy of individualized time interval from trigger to oocyte retrieval based on the magnitude of E2 increase after trigger.

Lower antimüllerian hormone is associated with lower oocyte yield but not live-birth rate among women with obesity

Antimüllerian hormone is produced by small antral follicles and reflects ovarian reserve. Obesity is associated with lower serum antimüllerian hormone, but it is unclear whether lower levels of antimüllerian hormone in women with obesity reflect lower ovarian reserve. To determine whether lower antimüllerian hormone in women with obesity undergoing invitro fertilization is associated with oocyte yield and live-birth rate. Retrospective cohort from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database of 13,316 women with obesity and 16,579 women with normal body mass index undergoing their first autologous invitro fertilization with fresh transfers between 2012 and 2014. Normal body mass index was defined as body mass index 18.5-24.9 kg/m2, and obesity was defined as body mass index ≥30 kg/m2. Subjects with obesity were stratified as those with class 1 obesity (body mass index, 30.0-34.9 kg/m2), class 2 obesity (body mass index, 35.0-39.9 kg/m2), and class 3 obesity (body mass index, ≥40 kg/m2) based on the World Health Organization body mass index guidelines. Antimüllerian hormone levels were stratified as normal (>1.1 ng/mL), low (0.16-1-1 ng/mL), and undetectable (≤0.16 ng/mL). Multivariable modeling was used to assess oocyte yield using linear regression with a logarithmic transformation and odds of live birth using logistic regression. Women with obesity were older (36.0 ± 4.8 vs 35.5 ± 4.8, P < .001), had lower antimüllerian hormone (1.8 ± 2.0 ng/mL vs 2.1 ± 2.0 ng/mL, P < .001), and had fewer oocytes retrieved (11.9 ± 7.3 vs 12.8 ± 7.7, P < .001) than women with normal body mass index. Lower oocyte yield was observed among women with obesity and normal antimüllerian hormone levels compared to women with normal body mass index and normal antimüllerian hormone levels (13.6 ± 7.3 vs 15.8 ± 8.1, P < .001). No difference in oocyte yield was observed among women with obesity and low antimüllerian hormone levels (P= .58) and undetectabl antimüllerian hormone (P= .11) compared to women with normal BMI and similar antimüllerian hormone levels. Among women with a body mass index ≥30 kg/m2, antimüllerian hormone levels were associated with the number of oocytes retrieved (β= 0.069; standard error, 0.005; P < .001) but not live-birth rate (odds ratio, 0.98; 95% confidence interval, 0.93-1.04, P= .57). Lower antimüllerian hormone in infertile women with obesity appears to reflect lower ovarian reserve, as antimüllerian hormone is associated with lower oocyte yield. Despite lower oocyte yield, lower antimüllerian hormone was not associated with lower live-birth rate among women with obesity.

Use of intracytoplasmic sperm injection (ICSI) in normospermic men may result in lower clinical pregnancy and live birth rates.

While intracytoplasmic sperm injection (ICSI) was developed for overcoming male infertility, it is increasingly being used for non-male factor indications, without consensus regarding the safety and efficacy of this approach. To determine whether ICSI offers any benefit compared to standard in vitro fertilisation (IVF), in the setting of normal semen parameters. Retrospective analysis of reproductive outcomes in 3363 stimulated cycles (IVF = 1661; ICSI = 1702), in patients treated between 2009-2015, was performed. Selected couples had no male factor infertility. Couples with abnormal semen parameters (based on WHO 2010 guidelines), presence of anti-sperm antibodies and low oocyte yield of ≤4 oocytes, were excluded. The outcomes analysed included: (1) fertilisation rate (FR); (2) clinical pregnancy rate (CPR); and (3) live birth rate (LBR), by method of fertilisation used (IVF vs ICSI) and controlling for significant confounders. FR, CPR and LBR were significantly higher in the IVF group compared with ICSI (67.1% vs 62.3%, 23.06% vs 16.8%, 17.22% vs 13.2%, respectively). Pregnancy rate with ICSI was approximately 30% lower than with IVF, even when controlling for significant factors such as day of embryo transfer and number of embryos transferred. This translates to one less pregnancy in every 15 cycles where ICSI was used without clear indication. Our data suggest that ICSI may be detrimental to clinical outcomes and contributes to the wider understanding of use of ICSI in normospermic men.

Highly Purified Human Menopausal Gonadotropin (Menopur®): A Profile of Its Use in Infertility

Menopur® is a highly purified, urine-derived, human menopausal gonadotropin containing both follicle stimulating hormone (FSH) and luteinizing hormone (LH) activity. It is an effective option for controlled ovarian stimulation (COS) in assisted reproductive technology protocols and for ovulation induction (OI) in anovulatory infertility, and is associated with a different endocrine profile from that of recombinant (r) FSH in these settings (in terms of serum levels of FSH, androgens and/or estradiol). When used for COS in women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), Menopur® was as good as rFSH in terms of pregnancy rates (despite being associated with a lower oocyte yield) and was found to improve some aspects of embryo quality in the IVF (but not ICSI) setting; using Menopur® in combination with highly purified urinary FSH resulted in similar reproductive outcomes as Menopur® alone. Data for Menopur® in OI are limited, but suggest ovulation rates may be as good as those with rFSH + rLH (in type 1 anovulation) and rFSH (in type 2 anovulation). Moreover, compared with rFSH, Menopur® appeared to be associated with a less pronounced follicular response and a lower risk of ovarian overstimulation.

Diminished ovarian reserve and poor response to stimulation in patients

Do infertile women aged <38 years with quantitative evidence of diminished ovarian reserve and/or poor response to stimulation also exhibit poor oocyte quality as measured by blastulation rates, aneuploidy rates, and live birth rates? Young women with evidence of accelerated follicular depletion, either by precycle ovarian reserve testing or postcycle evidence of low oocyte yield, exhibit equivalent blastulation rates, aneuploidy rates and live birth rates per euploid embryo transfer as age-matched controls with normal precycle and postcycle parameters. Previous studies are conflicted as to whether women with evidence of diminished ovarian reserve and/or poor ovarian response are also at increased risk of exhibiting evidence of poor oocyte quality. Most prior studies have failed to adequately control for the confounding effect of female age on typical markers of oocyte quality in poor responders. The rate of follicular depletion occurs at around 38 years on average; thus, evidence of quantitative depletion before this would indicate a premature diminution of ovarian reserve and allow evaluation of whether markers of oocyte quality are tied to quantitative markers. This was a retrospective cohort study at a single center between 2012 and 2016. This time frame was specifically chosen as all embryos were cultured to the blastocyst stage at this center during the study period (no cleavage stage transfers were performed). Two comparisons were made: precycle assessment of ovarian reserve (based on anti-mullerian hormone (AMH) level) and postcycle oocyte yield results. For each comparison, patients in <10th percentile were compared to patients in the interquartile range (IQR) with respect to blastulation rate, aneuploidy rate and live birth rate. A mixed effects model was created to control for female age (in the <38 year old range) and correlation among oocytes from a given cohort. For the precycle blastulation analysis, only patients with AMH data available were included (345 patients with AMH in the <10th percentile versus 1758 patients with AMH in the 25th to 75th percentile (IQR)). To compare aneuploidy rates, the subset of these patients who pursued preimplantation genetic testing for aneuploidy (PGT-A) was then analyzed (124 patients in the <10th percentile versus 782 patients in the IQR). For the postcycle blastulation analysis, all patients who proceeded to retrieval (whether or not they also had AMH data available) were included (535 patients with oocyte yield in the <10th percentile versus 2675 patients in the IQR). To compare aneuploidy rates, the subset of these patients who pursued PGT-A was then analyzed (156 patients in the <10th percentile versus 1100 patients in the IQR). The adjusted odds of a given fertilized oocyte developing to a blastocyst, being aneuploid or leading to a live birth after euploid transfer were no different if the oocyte was retrieved from a cycle with ovarian reserve parameters or oocyte yield in the <10th percentile compared to an oocyte retrieved in a cycle with those parameters in the 25-75th percentile. An AMH level in the <10th percentile did more commonly result in cycle cancellation prior to retrieval and after retrieval prior to transfer due to global arrest of embryos. The timing of retrieval in patients with fewer oocytes may be more optimal given the greater ability to discern the overall maturity of the cohort, thus enhancing performance per retrieved oocyte. Analyses included only first cycles. Subsequent adjustment of protocol due to prior performance may mean that some patients in the <10th percentile for oocyte yield are actually better prognosis patients than their first cycle indicates. Data on whether or not patients were on oral contraceptives at time that AMH level drawn was not available. Other unknown biases are also likely to be present given retrospective nature of the study. While young women with evidence of quantitative depletion of ovarian reserve have lower live birth rates per stimulation cycle, this not attributable to poor oocyte quality because the blastulation rate per fertilized oocyte and live birth rate per embryo transfer are equivalent to that in women with normal quantitative markers of ovarian reserve. Thus, the pathophysiology mediating a premature quantitative decline in ovarian reserve appears different than that which mediates markers of oocyte quality, such as aneuploidy. Young poor responders may use this information to help guide embryo accumulation strategies when considering their family building plans. None. N/A.

Fertility preservation: ovarian response to freeze oocytes is not affected by different malignant diseases-an analysis of 992 stimulations.

To study if ovarian response is affected by the type of disease if fertility preservation is required. A registry of the trinational fertility preservation network FertiPROTEKT including 992 patients aged 18-40years undergoing ovarian stimulation and follicle aspiration for fertility preservation from 1/2007 until 3/2016 was analysed. The number of collected oocytes, days of stimulation, total gonadotropin dosage and gonadotropin dosage per day were evaluated. Total oocyte number was negatively correlated with increasing age (r = 0.237, p < 0.0001). Oocyte numbers were in women < 26years 15.4 ± 8.8, 26-30years 13.1 ± 8.5, 31-35years 12.2 ± 7.7 and 36-40years 9.9 ± 8.0. Age-adjusted oocyte numbers were not different in women with Hodgkin's lymphoma (12.6 ± 8.8), non-Hodgkin's lymphoma (12.4 ± 8.2), leukaemia (11.7 ± 8.2), sarcoma (11.8 ± 8.2), cerebral cancer (16.5 ± 8.1), gastrointestinal cancer (13.2 ± 8.1) gynaecological cancer (10.8 ± 8.2) and other types of malignancies (15.8 ± 8.1) apart from ovarian cancer with lower oocyte yield (7.3 ± 8.3, p < 0.001) compared to women with breast cancer (13.3 ± 8.8). The total gonadotropin dose used for stimulation was only elevated in Hodgkin's and non-Hodgkin's lymphoma compared to women with breast cancer (p < 0.05). Oocyte yield was lower in women with versus without ovarian cancer (p < 0.0001). As ovarian response is not affected by the type of cancer, ovarian stimulation can be performed with the same oocyte yield in different malignant diseases. However, oocyte yield is reduced if ovarian surgery is required and in older women.

Progestin-primed milder stimulation with clomiphene citrate yields fewer oocytes and suboptimal pregnancy outcomes compared with the standard progestin-primed ovarian stimulation in infertile women with polycystic ovarian syndrome

BackgroundOral progestin has recently been used to prevent premature LH surges in ovarian stimulation, and this progestin-primed ovarian stimulation (PPOS) is effective and safe in patients with different ovarian reserves. The current data are lacking regarding how to individualize the gonadotropin dose and regimen for women with polycystic ovarian syndrome (PCOS). A retrospective cohort trial was performed to evaluate the efficacy of progestin-primed milder stimulation with clomiphene citrate (CC) compared to the standard progestin-primed ovarian stimulation (PPOS) protocol for infertile women with PCOS.MethodsA total of 220 PCOS women were collected and classified into the study group (HMG 150 IU/d + CC 50 mg/d + MPA 10 mg/d) and control group (HMG 225 IU/d + MPA 10 mg/d). Ovulation was triggered by GnRH agonist 0.1 mg and hCG 1000 IU when dominant follicles matured. Viable embryos were cryopreserved for later transfer. The primary endpoint was the ongoing pregnancy rate. Secondary outcomes included the cycle characteristics and the live birth rate.Result(s)The study group consumed less HMG (1470.0 ± 360.1 IU vs 1943.8 ± 372.0 IU, P < 0.001) and harvested fewer oocytes than the control group (12.2 ± 7.4 vs 18.2 ± 9.7, P < 0.001). The study group showed a higher mid-follicular LH concentration (4.49 ± 2.49 mIU/ml vs 2.52 ± 2.09 mIU/ml, P < 0.05) but no endogenous LH surge. No between-group difference was found in the incidence of ovarian hyperstimulation syndrome (OHSS) (0.91% vs 0.91%, P > 0.05). The cumulative ongoing pregnancy rate and live birth rate per patient were lower but did not reach significance compared with the control group (71.8% vs 81.8 and 64.5% vs 75.5%, respectively, both P > 0.05).Conclusion(s)The milder PPOS with CC in PCOS women led to lower oocyte yields and suboptimal pregnancy outcomes compared to the standard PPOS treatment. The two regimens both achieved a low incidence of OHSS. The results from the CC combination regimen provide a new insight for developing a more patient-friendly protocol for PCOS women.

Dual trigger of final oocyte maturation in poor ovarian responders undergoing IVF/ICSI cycles

Previous studies show that a dual trigger ovulation regimen significantly improves number and maturity of retrieved oocytes for normal ovarian responders or patients with history of low oocyte yield. The current retrospective cohort study investigated whether dual trigger of final oocyte maturation may benefit IVF outcomes for poor ovarian responders fulfilling the Bologna criteria. Undertaken between May 2014 and August 2016, the study involved 1350 patients undergoing 1389 IVF/intracytoplasmic sperm injection treatment cycles. Patients triggered with 5000 IU human chorionic gonadotrophin (HCG) alone (328 cycles) were compared with those undergoing dual triggering with 5000 IU HCG plus 0.1 mg gonadotrophin-releasing hormone agonist (GnRHa) (386 cycles) and patients triggered with 10,000 IU HCG (363 cycles) were compared with those undergoing dual triggering with 10,000 IU HCG plus 0.1 mg GnRHa (312 cycles). The dual trigger groups showed significantly higher number of oocytes collected and number of mature oocytes compared with their respective HCG trigger group (P < 0.001). Oocyte retrieval rate and percentage of mature oocytes retrieved were also both significantly higher in the dual trigger groups (P < 0.001). Fertilization rate, number of viable embryos, implantation rate, clinical pregnancy rate and miscarriage rate were not significantly different between groups.

Low oocyte yield during IVF treatment and the risk of a trisomic pregnancy

A low number of antral follicles may result in the selection of suboptimal oocytes that are prone to meiotic errors. The aim of this case-control study was to evaluate women receiving IVF treatment with low oocyte yield (defined as three or fewer oocytes retrieved after ovarian stimulation) who are at an increased risk of a trisomic pregnancy. Data were obtained from Danish and Dutch medical registries between 1983 and 2011. Analyses were carried out in 105 cases and 442 controls matched by age and year of IVF treatment. Cases were women with a trisomic pregnancy (trisomies 13, 18 or 21) resulting from fresh IVF treatment and confirmed by karyotyping. Cases were included regardless of pregnancy outcome. Controls were women with a live born child without a trisomy, resulting from fresh IVF treatment. Low oocyte yield was observed in 6.6% (29/440) of the women, of which 8.4% (7/83) were cases and 6.2% (22/357) controls. Low oocyte yield in IVF treatment was not associated with a higher risk of trisomic pregnancy (OR 1.43, 95% CI 0.64 to 3.19). Stratification for female age, adjustment for history of ovarian surgery, and gonadotrophin-releasing hormone protocol used did not change the results.

Is day 3 follicle stimulating hormone (fsh) useful in patients with normal antimullerian hormone (AMH) and antral follicle count (AFC)?

Obtaining an early follicular phase serum FSH can be an inconvenience to patients, lead to increased costs and delay infertility treatments. The goal of this study was to determine the utility of the cycle day 3 FSH in patients with otherwise normal ovarian reserve tests. Retrospective cohort study. A review of patient's records who underwent IVF from 2012 to 2015 was performed. Subjects included in the study had AMH levels ≥1 ng/ml and AFC ≥10. Cycle day 3 serum FSH levels were categorized into three separate groups: high ≥10 IU/L, normal >5 IU/L and< 10 IU/L, and low ≤5 IU/L. Subjects with an elevated day 3 estradiol (≥80 ng/mL) obtained at the time of FSH and high responders (AMH ≥10 ng/ml and/or AFC ≥30) were excluded. Baseline demographics and IVF cycle parameters and outcomes were compared among the three groups using ANOVA and chi-square test where applicable. A total of 225 subjects were identified. The majority of the subjects (91%) utilized a GnRH antagonist cycle, and type of cycle utilized was not different based on FSH group (p=0.84). Those in the high group received a higher mean total dose of gonadotropins (3977 IU) compared to the normal (3335 IU) and low groups (3746 IU) (p=0.01). Comparison among the three groups is presented in table 1.Table 1Comparison of three FSH groupsHigh (n=36)Normal (n=170)Low (n=19)p valueAge33.3 ± 4.532.9 ± 4.631.2 ± 5.50.26BMI24 ± 426 ± 628 ± 70.06AMH2.6 ± 1.52.9 ± 1.63.2 ± 2.10.38AFC18 ± 519 ± 620 ± 50.19% started on 450 IU13 (36%)33 (19%)7 (37%)0.001*Peak estradiol (pg/ml)2270255323870.36No. of follicles recruited17 ± 1022 ± 925 ± 100.01*No. of oocytes retrieved15 ± 818 ± 921 ± 80.02*No. of 2PN embryos8 ± 410 ± 612 ± 50.04*Clinical pregnancy rate13/25 (52%)71/113 (63%)3/6 (50%)0.53Live birth rate10/25 (40%)53/113 (47%)2/6 (33%)0.69 Open table in a new tab An isolated elevated cycle day 3 FSH was associated with decreased follicular development and lower oocyte yield despite normal AMH and AFC. Although clinical pregnancy rate and live birth rate were not different statistically when looking at a single cycle, this may impact cumulative pregnancy rates and long term outcomes for these patients. Based on the findings from this study, we will continue to recommend a complete ovarian reserve evaluation to determine the of optimal initial gonadotropin dose and properly counsel patients on IVF outcomes.

Lower AMH is associated with lower oocyte yield and live birth rate among obese women; analysis of 36,334 IVF cycles

Lower AMH is associated with lower oocyte yield and live birth rate among obese women; analysis of 36,334 IVF cycles

Stimulation and aneuploidy: Why are milder stimulation protocols better?

There is an ever-increasing trend in assisted reproductive techniques to reduce the intensity of ovarian stimulation for in vitro fertilization (IVF) and to restrict the number of embryos that are transferred into the uterine cavity. Recent findings suggest that the magnitude of ovarian stimulation affects the proportion of euploid embryos. Ovarian stimulation regimens for IVF seem to have a deleterious effect on oocyte quality and embryo aneuploidy in a dose-dependent manner. We are moving to a global era of single embryo transfers and now it becomes more important than ever before to ensure that this single embryo has the highest implantation potential. Strategies are being adopted to improve the accuracy for selecting euploid, viable embryos for transfer. One such strategy involves further refinement of morphological criteria associated with improved viability by considering, for example, pronuclei disposition, nucleolar organization, and identification of the fast-cleaving embryos, with only mononucleate blastomeres and trying to correlate morphokinetics with cytogenetics. Another strategy employs preimplantation genetic diagnosis whereby a biopsied blastomere is tested for ploidy using next-generation sequencing. Even in older patients, lower oocyte yields may represent a more appropriate response to ovarian stimulation, allowing the most competent follicles and oocytes to develop and thereby reducing the occurrence of embryo aneuploidy. IVF Lite plus ACCUVIT by repeated mild stimulation cycles with subsequent vitrification of blastocysts, combined with preimplantation genetic screening, is a promising new approach for poor responders as well as women of advanced maternal age.

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study.

Background:Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes.Objective:We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART).Methods:This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004–2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman.Results:In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were –0.19 (–0.29, –0.08) and –0.19 (–0.28, –0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites.Conclusions:Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART.Citation:Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831–839; http://dx.doi.org/10.1289/ehp.1509760

Outcomes of ovarian stimulation after treatment with chemotherapy.

Chemotherapeutic agents have a known gonadotoxic effect; however, it is difficult to predict the impact they may have on ovarian stimulation. The objective of this study was to evaluate response to ovarian stimulation in patients exposed to chemotherapy compared with patients who were chemotherapy-naïve. A retrospective cohort study of 130 patients with cancer or autoimmune disease was performed. Demographics, ovarian reserve, ovarian response and stimulation parameters, and oocyte data were compared between patients who were pre- and post-chemotherapy. Logistic regression modeling was performed to identify risk factors for cancellation and low oocyte yield, adjusting for confounders as appropriate. Antral follicle count (AFC) was significantly lower in post-chemo patients (9 vs. 17, p < 0.001). Post-chemotherapy patients were more likely to be cancelled during stimulation (23 vs. 4 %, p = 0.003). Among those that went to retrieval, there was no difference in total number of oocytes (10 vs. 10, p = 0.31) or mature oocytes retrieved (8 vs. 8, p = 0.38), despite higher starting (300 vs. 450 IU, p < 0.001) and total gonadotropin (3075 vs. 4612.5 IU, p = 0.008) doses in post-chemotherapy patients. Low AFC (≤6) was associated with cycle cancellation (OR 7.7, 95 % CI 1.8-33.2) and low oocyte yield (<6) (OR 5.4, 95 % CI 1.6-17.7). Patients post-chemotherapy have lower AFC compared with the chemotherapy-naïve and have higher cancellation rates. Among those who underwent oocyte retrieval, oocyte yield was similar in both groups. Low AFC was most strongly associated with cycle cancellation and oocyte yield. Post-chemotherapy patients had higher rates of cycle cancellation but did equally well as pre-chemotherapy patients if they reached retrieval.

Trends in Use of and Reproductive Outcomes Associated With Intracytoplasmic Sperm Injection

Since its introduction in 1992, intracytoplasmic sperm injection (ICSI) has been increasingly used in patients without severe male factor infertility despite the lack of clear evidence of a benefit over conventional in vitro fertilization (IVF). Compared with pregnancies resulting from conventional IVF, pregnancies resulting from the use of ICSI are associated with 1.5 to 4 times increased risk of chromosomal abnormalities, birth defects, intellectual disabilities, imprinting disorders, and autism. Intracytoplasmic sperm injection is considerably more expensive than conventional IVF. The aim of this retrospective observational study was to assess national trends and reproductive outcomes of fresh IVF cycles associated with the use of ICSI compared with conventional IVF with respect to clinical indications for ICSI use. Although only fresh embryos were transferred, it is unlikely that outcomes for frozen-thawed embryos would differ. Data were obtained from the US National Assisted Reproductive Technology Surveillance System for all fresh and ICSI cycles performed during 1996 to 2012. The primary study outcomes were (1) trends in use of ICSI during 1996 to 2012 with respect to male factor infertility, unexplained infertility, maternal age 38 years or older, low oocyte yield (<5 oocytes retrieved), and 2 or more prior assisted reproductive technology cycles and no prior live birth, and (2) reproductive outcomes during 2008 to 2012 for conventional IVF and ICSI cycles, stratified by the presence or absence of male factor infertility. A total of 1,395,634 fresh IVF cycles were identified between1996 and 2012; 908,767 (65.1%) used ICSI, and 486,867 cycles (34.9%) used conventional IVF. Male factor infertility was identified in 499,135 (35.8%) of fresh cycles. During 2006 to 2012, ICSI use among cycles with male factor infertility increased from 76.3% (10,876/14,259) to 93.3% (32,191/34,506) (P < 0.001), whereas its use for those without male factor infertility increased from 15.4% (4,197/27,191) to 66.9% (42,321/63,250) (P < 0.001). During 2008 to 2012, 494,907 fresh IVF cycles were identified, 74.6% of which used ICSI. Male factor infertility was reported in 35.7% (176,911/494,907) of fresh cycles. The risk for multiple births among these cycles was significantly lower in those undergoing ICSI compared with conventional IVF (30.9% vs 34.2%); the adjusted relative risk (RR) was 0.87, with a 95% confidence interval (CI) of 0.83 to 0.91. Compared with conventional IVF, ICSI use among cycles without male factor infertility (n = 317,996) was associated with lower rates of implantation (23.0% vs 25.2%; adjusted RR, 0.93; 95% CI, 0.91–0.95), live birth (36.5% vs 39.2%; adjusted RR, 0.95; 95% CI, 0.93–0.97), and multiple live births (30.1% vs 31.0%; adjusted RR, 0.93; 95% CI, 0.91–0.95). These findings show that ICSI use among fresh IVF cycles in the United States increased from 36.4% to 76.2% between 1996 and 2012. The largest relative increase occurred in cycles without male factor infertility. The data show no improvement in postfertilization reproductive outcomes with use of ICSI over conventional IVF in the absence of male factor infertility, irrespective of male factor infertility diagnosis.

The need to improve patient care through discriminate use of intracytoplasmic sperm injection (ICSI) and improved understanding of spermatozoa, oocyte and embryo biology

D. T. Carrell, A. Nyboe Andersen and D. J. Lamb Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA, The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, and The Center for Reproductive Medicine, Scott Department of Urology and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Low antral follicle count (AFC) is linked to cycle cancellation and low oocyte yield in patients treated with chemotherapy

Chemotherapeutic agents have a known gonadotoxic effect. However it can be difficult to predict the exact impact these drugs may have on response to ovarian stimulation. Few studies have evaluated the success of assisted reproductive treatment (ART) in patients who have been exposed to chemotherapy.

Stages of endometriosis: Does it affect in vitro fertilization outcome

ObjectiveWomen with endometriosis often need in vitro fertilization (IVF) to conceive. There are conflicting data on the results of IVF in patients with endometriosis. The present study was undertaken to investigate whether or not the stage of endometriosis affects the IVF outcome in order to give the best patient counseling Materials and methodsWe compared IVF outcome measures between 40 patients with surgically confirmed minimal and mild endometriosis (American Society for Reproductive Medicine Stage I/II) and 38 patients with moderate and severe endometriosis (Stage III/IV). Each group was also compared with a control group of 157 patients with tubal factor infertility. Outcome measures included number of follicles, number of oocytes, mean number of ampoules of gonadotropins, cumulative pregnancy, and live birth rates ResultsHigher cancelation rates, higher total gonadotropin requirements, and lower oocyte yield were found in women with endometriosis Stage III and IV compared with both the Stage I/II and control groups. The fertilization rate was higher in Stage III/IV endometriosis compared to Stage I/II. Clinical pregnancy and live birth rates were comparable between patients with endometriosis Stage I/II and control group, whereas they were significantly lower in patients with endometriosis Stage III/IV compared to other two groups. ConclusionThe American Society for Reproductive Medicine classification of endometriosis is useful in predicting IVF outcome. Advanced endometriosis means a worse prognosis for IVF treatment compared to milder stages or tubal factor infertility. The decreased fertilization rate in Stage I/II endometriosis might be a cause of subfertility in these women, as a result of a hostile environment caused by the disease.

Can intracytoplasmic sperm injection prevent total fertilization failure and enhance embryo quality in patients with non-male factor infertility?

ObjectiveTo determine whether intracytoplasmic sperm injection (ICSI) could prevent total fertilization failure (TFF) and enhance the embryo quality in patients with non-male factor infertility. Study designA total of 296 in vitro fertilization (IVF) cycles performed in patients with non-male factor infertility between April 2009 and March 2013 were included in this retrospective study. During the period, ICSI and conventional IVF were performed in 142 and 154 cycles, respectively. The usual indications for ICSI were in the cycles of patients with (1) known low fertilization rate, (2) repetitive implantation failure, (3) advanced maternal age, (4) presence of endometrioma, (5) low oocyte yield (number of oocytes ≤3), or (6) poor quality oocytes. The rate of TFF, normal fertilization, abnormal pronuclei (PN) formation, embryo quality, and pregnancy outcomes between the patients treated with ICSI and conventional IVF cycles were compared. ResultsThe patients treated with ICSI (ICSI group, n=142) presented fewer number of oocytes than patients treated with conventional IVF cycles (n=154). The TFF rate was not different (4.2% vs. 0.6%, P=0.059), but the ICSI group presented a significantly higher rate of normal fertilization (83.4% vs. 79.1%, P=0.04) and lower rate of abnormal PN formation (3.9% vs. 13.3%, P<0.01). The cleavage stage embryo quality was better in the ICSI group (grade A: 31.1% vs. 21.3%, P=0.001; grade A+B: 65.1% vs. 47.6%, P<0.001). ConclusionThe result of this study does not support the use of ICSI to prevent TFF in patients with non-male factor infertility. However, ICSI improved the fertilization rate and the embryo quality.

Risk Factors for Failure to Respond to GnRH Agonist Trigger in Fresh In Vitro Fertilization Cycles

Gonadotropin-releasing hormone (GnRH) agonists are often used to trigger ovulation during IVF in order to decrease the risk of ovarian hyperstimulation syndrome in high responders. Administration of a GnRH agonist trigger in antagonist cycles causes an endogenous LH surge that promotes follicular maturation prior to oocyte retrieval. Rare instances of failure to mount an appropriate LH surge in response to an agonist trigger have been reported, an event associated with decreased oocyte maturity, low oocyte yield, and compromised cycle outcomes.