Intracytoplasmic sperm injection 30 years on: too much of a good thing?

Intracytoplasmic sperm injection (ICSI) was introduced for male infertility but is now used in many other techniques in assisted reproduction. Indications for ICSI use need to be re-evaluated to ensure appropriate application in infertility management.

More blastocysts are produced from fewer oocytes in ICSI compared to IVF - results from a sibling oocytes study and definition of a new key performance indicator.

BACKGROUND: Which fertilization method, between ICSI and IVF in split insemination treatments, has the highest clinical efficiency in producing clinically usable blastocyst? METHODS: 211 infertile couples underwent split insemination treatments for a non-severe male factor. 1300 metaphase II (MII) oocytes were inseminated by conventional IVF and 1302 MII oocytes were micro-injected with the same partner's semen. Embryo development until blastocyst stage on day V and clinical outcomes were valuated trough conventional key performance indicators (KPI), and new KPIs such as blastocyst rate per used MII oocytes and the number of MII oocytes to produce one clinically usable blastocyst from ICSI and IVF procedures. RESULTS: The results were  globally analyzed and according to ovarian stimulation protocol, infertility indication, and female age. The conventional KPI were online with the expected values from consensus references. From global results, 2.3 MII oocyte was needed to produce one clinically usable blastocyst after ICSI compared to 2.9 MII oocytes in IVF. On the same way, more blastocysts for clinical use were produced from fewer MII oocytes in ICSI compared to IVF in all sub-groups. CONCLUSIONS: In split insemination treatments, the yield of clinically usable blastocysts was always superior in ICSI compared to IVF. The new KPI "number of needed oocytes to produce one clinically usable embryo" tests the clinical efficiency of the IVF laboratory.

Sperm selection during ICSI treatments reduces single- but not double-strand DNA break values compared to the semen sample.

PURPOSE: To detect a possible bias in sperm DNA fragmentation (SDF) testing when performed on semen samples or on those few spermatozoa selected for Intracytoplasmic Sperm Injection (ICSI) treatments. METHODS: A multimethodological analysis of Single- and Double-Strand DNA Breaks (SSB and DSB, respectively) was performed through the Neutral Comet, the Alkaline Comet, the Sperm Chromatin Dispersion (SCD) and the Terminal deoxynucleotidyl transferase dUTP Nick End Labelling (TUNEL) assays. SDF was evaluated in (i) semen samples from 23 infertile patients (not achieving pregnancy or suffering recurrent miscarriage); (ii) samples after a Swim-up and (iii) spermatozoa microselected for ICSI (ICSI-S). RESULTS: The analysis of 3217 ICSI-S revealed a significant reduction of SSB values compared to the Ejaculate and the Swim-up samples. On the contrary, DSB values were not reduced after any sperm selection method. The No-pregnancy group presented poorer semen parameters and higher SSB values. The Recurrent miscarriage group presented better semen parameters but also higher DSB values. CONCLUSION: The analysis of SDF on semen samples may not be fully representative of those few spermatozoa selected for ICSI. Since oxidative stress impairs sperm motility and causes SSB, selecting a motile sperm may intrinsically imply choosing a sperm not affected by this damage. DSB have an enzymatic origin which does not affect motility, making it difficult to select a sperm without this damage. Therefore, ICSI treatments could be effective in patients presenting high SSB values. Patients presenting high DSB values should expect bad ICSI results if this damage is not reduced through other specific methods.

Early rescue oocyte activation for activation-impaired oocytes with no second polar body extrusion after intracytoplasmic sperm injection.

PURPOSE: When rescue artificial oocyte activation (ROA) is performed on the day after intracytoplasmic sperm injection (ICSI) or later, embryonic development is poor and seldom results in live births. The efficacy of an early ROA after ICSI is unclear. Is early ROA effective in rescuing unfertilized oocytes that have not undergone second polar body extrusion several hours after ICSI? METHODS: We performed retrospective cohort study between October 2016 and September 2019, targeting 2891 oocytes in 843 cycles when ICSI was performed. We performed ROA with calcium ionophore on 395 of the 475 oocytes with no second polar extrusion 2.5-6 h after ICSI. RESULTS: The normal fertilization rate of ROA oocytes was significantly higher than non-ROA oocytes (65.8% vs 6.7%, P < 0.001). The blastocyst development rate in ROA oocytes was significantly lower than spontaneously activated oocytes (48.9% vs 67.2%, P < 0.001). The ROA oocyte implantation rate did not significantly differ from the spontaneously activated oocytes (36.0% vs 41.2%). We observed no differences in the implantation rates and blastocyst development rates over the 2.5-6 h from ICSI until ROA. CONCLUSION: Early ROA is effective, and the optimal timing appears to be 2.5-6 h after ICSI.

Evolution of cumulative live birth and dropout rates over six complete IVF/ICSI cycles: a large prospective cohort study.

RESEARCH QUESTION: How do cumulative live birth rates (CLBR), cumulative multiple live birth rates (CMLBR) and dropout rates over six IVF and intracytoplasmic sperm injection (ICSI) cycles change over time? DESIGN: Prospective longitudinal cohort (n = 16,073 patients; 48,946 cycles) starting a first fresh assisted reproductive technology cycle between 1 January 2014 and 31 December 2016, with follow-up until 31 December 2017. Outcomes between the periods 2014-2017 and 2009-2012 were compared. RESULTS: Conservative estimates of CLBR after six complete cycles were significantly higher in women younger than 35 years after every cycle: one to three, adjusted P-value [p adj] < 0.0001; four, p = 0.01; five, p adj = 0.03; six, p adj = 0.04) and after the first cycle in women aged 35-37 years (p adj = 0.04) in 2014-2017 versus 2009-2012. For an optimal estimate, the CLBR was significantly higher after the first three cycles in women younger than 35 years (all p adj < 0.0001) and after the first cycle in women aged 35-37 years (p adj = 0.04). The CMLBR rate decreased from 5.1% ± 0.19 (SE) to 4.1% ± 0.16 for the conservative estimate and from 8.6% ±0.37 (SE) to 6.7% ± 0.30 for the optimal estimate after six complete cycles for the whole cohort. Dropout rates of complete cycles were 26.5% 29.4%, 33.4%, 38.9% and 47.3% after the first to fifth cycle, respectively. Compared with 2009-2012, the dropout rate in the current period was significantly higher for the first (P < 0.0001) and second (P = 0.0124) cycle. CONCLUSION: Over six complete IVF/ICSI cycles, CLBR and dropout rates increased and multiple live birth rates decreased when 2014-2017 was compared with 2009-2012.

Growth hormone supplementation during ovarian stimulation improves oocyte and embryo outcomes in IVF/PGT-A cycles of women who are not poor responders.

PURPOSE: To determine the effect of human growth hormone (GH) supplementation during ovarian stimulation in women undergoing IVF/PGT-A cycles, who do not meet the Bologna criteria for poor ovarian response (POR). METHODS: This is a retrospective cohort study of 41 women with suboptimal outcomes in their first cycle of IVF/PGT-A including lower than expected number of MII oocytes, poor blastulation rate, and/or lower than expected number of euploid embryos for their age, who underwent a subsequent IVF/PGT-A cycle with the same fixed dose gonadotropin protocol and adjuvant GH treatment. Daily cotreatment with GH started with first gonadotrophin injection. The IVF cycle outcomes were compared between the control and GH cycle using the Wilcoxon-Signed Rank test. RESULTS: The total number of biopsied blastocysts (mean ± SD; 2.0 ± 1.6 vs 3.5 ± 3.2, p = 0.009) and euploid embryos (0.8 ± 1.0 vs 2.0 ± 2.8, p = 0.004) were significantly increased in the adjuvant GH cycle compared to the control cycle. The total number of MII oocytes also trended to be higher in the GH cycle (10.2 ± 6.3 vs 12.1 ± 8.3, p = 0.061). The overall blastulation and euploidy rate did not differ between the control and treatment cycle. CONCLUSION: Our study uniquely investigated the use of adjuvant GH in IVF/PGT-A cycles in women without POR and without a priori suspicion for poor outcome based on their clinical parameters. Our study presents preliminary evidence that GH supplementation in these women is beneficial and is associated with an increased number of blastocysts for biopsy and greater number of euploid embryos for transfer.

Round spermatid injection into human oocytes: a systematic review and meta-analysis.

Many azoospermic men do not possess mature spermatozoa at the time of surgical sperm extraction. This study is a systematic review and meta-analysis evaluating outcomes following round spermatid injection (ROSI), a technique which utilizes immature precursors of spermatozoa for fertilization. An electronic search was performed to identify relevant articles published through October 2018. Human cohort studies in English involving male patients who had round spermatids identified and used for fertilization with human oocytes were included. Fertilization rate, pregnancy rate, and resultant delivery rate were assessed following ROSI. Meta-analysis outcomes were analyzed using a random-effects model. Data were extracted from 22 studies involving 1099 couples and 4218 embryo transfers. The fertilization rate after ROSI was 38.7% (95% confidence interval [CI]: 31.5%-46.3%), while the pregnancy rate was 3.7% (95% CI: 3.2%-4.4%). The resultant delivery rate was low, with 4.3% of embryo transfers resulting in a delivery (95% CI: 2.3%-7.7%). The pregnancy rate per couple was 13.4% (95% CI: 6.8%-19.1%) and the resultant delivery rate per couple was 8.1% (95% CI: 6.1%-14.4%). ROSI has resulted in clinical pregnancies and live births, but success rates are considerably lower than those achieved with mature spermatozoa. While this technique may be a feasible alternative for men with azoospermia who decline other options, couples should be aware that the odds of a successful delivery are greatly diminished and the prognosis is relatively poor.

Faster fertilization and cleavage kinetics reflect competence to achieve a live birth after intracytoplasmic sperm injection, but this association fades with maternal age.

OBJECTIVE: To assess the relationship of early developmental kinetics with competence to provide a live birth and the impact of maternal age in this context. DESIGN: Retrospective cohort study including 4,915 embryos, of which 1,390 were transferred and provided a clinical outcome paired with morphokinetic data; 168 of them resulted in a live birth (LB), and 1,222 did not (NLB). Early morphokinetic parameters were compared between LB and NLB embryos from patients stratified into two age groups (<37 and ≥37 years), and between embryos at the same competence group from patients aged <37 and ≥37 years. The association of morphokinetic parameters with live birth was tested by univariate and multivariate analyses. SETTING: Fertility clinic. PATIENT(S): The study population included 1,066 patients undergoing autologous intracytoplasmic sperm injection cycles with fresh single (SET), double (DET) or triple (TET) embryo transfers on day 2 or 3. Of them, 669 patients produced NLB embryos and 134 produced LB embryos. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization and cleavage morphokinetic parameters and live birth. RESULT(S): In the total patient population, all morphokinetic parameters were achieved earlier in LB compared with NLB embryos. The same was observed in patients aged <37 years (P<.015), but not ≥37 years. Except for the t8 (time at which an 8-blastomere embryo was identified), all morphokinetic parameters were reached earlier in LB embryos from patients aged <37 years compared with LB embryos from patients aged ≥37 years. Univariate analysis revealed that earlier occurrence of all morphokinetic parameters was associated with live birth, although only earlier t2 (time at which two separate and distinct cells were identified) was associated with live birth independently from maternal age in the multivariate analysis. CONCLUSION(S): Despite its retrospective nature and performance in a single IVF center, this study presents novel data indicating that embryos competent to provide a live birth display overall faster early developmental kinetics compared with embryos that do not achieve a live birth after transfer, a difference that, however, narrows as maternal age advances. The findings suggest that fertilization and cleavage morphokinetic parameters may constitute valuable references for embryo selection strategies aiming to improve live birth rates, specifically before advanced maternal age while holding limited usefulness in advanced maternal age.

Shorter telomere length of white blood cells is associated with higher rates of aneuploidy among infertile women undergoing in vitro fertilization.

OBJECTIVE: To evaluate whether the telomere length of white blood cells (WBC) and cumulus cells (CC) in an infertile population is associated with ovarian and embryonic performance. DESIGN: Prospective cohort study. SETTING: Academic-affiliated private practice. PATIENTS: A total of 175 infertile women undergoing in vitro fertilization (IVF) at a single center between July 2017 and December 2018. INTERVENTIONS: On the day of oocyte retrieval, genomic DNA was isolated from WBC and CC samples. Telomere length assessment was performed for both tissue types using quantitative real-time polymerase chain reaction. Telomere lengths were normalized using an AluYa5 sequence as an endogenous control, and linear regressions were applied. MAIN OUTCOME MEASURES: This study assessed the relationship between relative telomere length of WBC and CC samples and measures of ovarian and embryonic performance. Specifically, patient age, antimüllerian hormone (AMH) level, peak estradiol (E2) level, number of oocytes retrieved, number of mature (MII) oocytes retrieved, blastulation rate, and aneuploidy rate were assessed. RESULTS: There was a statistically significant relationship between WBC relative telomere length and patient age as well as rates of embryonic aneuploidy, with shorter WBC relative telomere length associated with increasing patient age (P<.01) and higher rates of aneuploidy (P=.01). No statistically significant relationships were observed between WBC relative telomere length and the other outcome measures. No significant associations were noted between CC relative telomere length and any outcomes assessed in this study. CONCLUSION: The relationship between WBC relative telomere length and aneuploidy warrants further investigation, particularly because significant overlap exists between increasing maternal age and rates of embryonic aneuploidy.

Three hour abstinence as a treatment for high sperm DNA fragmentation: a prospective cohort study.

PURPOSE: This study sought to compare sperm DNA fragmentation (SDF) in semen specimens after 3 days and then after 3 h of abstinence in men presenting for initial infertility evaluation. METHODS: A prospective cohort study of 112 men undergoing their first semen analysis as part of an infertility work-up was conducted. All participants presented with 3 days of abstinence for a semen analysis and DNA-fragmentation test. Both tests were repeated on a second sample collected 3 h after the first ejaculation. DNA-fragmentation was evaluated with the halo test by one of two technicians blinded to duration of abstinence. Variables analyzed include ejaculate volume, sperm concentration and motility, smoking status, cannabis use, initial specimen DNA fragmentation, and use of sperm-directed anti-oxidant formulations. RESULTS: Among all subjects, DNA fragmentation improved in the 3-h abstinence specimen (34.6 ± 19.4% vs. 23.7 ± 16.0%, p = 0.0001). Among subjects with high DNA fragmentation (> 35%) on the initial specimen, 55% improved into the normal range. Semen volume and sperm concentration decreased (3.1 ± 3.3 ml vs. 1.9 ± 0.8 ml, p < 0.01 and 41 ± 39 vs. 32 ± 31 (millions/ml), p = 0.01), while progressive motility tended to increase. Fifty-eight subjects demonstrated ≥ 30% improvement in SDF in the second specimen as compared to the first. Factors found to correlate with > 30% improvement in DNA fragmentation in the 3-h abstinence specimen compared to 3 days were younger age and use of anti-oxidants. CONCLUSION: High SDF can often be managed with a second ejaculation 3 h after the first in infertile couples, including in males with abnormal semen analyses per the 2010 WHO guide. Apart from SDF levels, changes in sperm quality were not clinically significant in the second specimen and did not increase rates of ICSI. However, a second ejaculation after 3 h probably may reduce the necessity of costly and/or invasive ART strategies.

Thoughts on the popularity of ICSI.

PURPOSE: Intracytoplasmic sperm injection (ICSI) is the most widely utilized assisted reproductive technique (ART) worldwide. In this feature, we review the early assisted fertilization attempts that eventually led to the development of ICSI, and discuss its current utilization in cases of male and non-male factor infertility. METHODS: We researched the literature related to the development, indications, and current use of ICSI, such as sperm structural abnormalities, male genetic indications, surgically retrieved sperm, high sperm chromatin fragmentation, oocyte dysmorphism, and preimplantation genetic testing (PGT). We also describe the potential future applications of ICSI. RESULTS: This review summarizes the early micromanipulation techniques that led to the inception of ICSI. We also explore its current indications, including non-male factor infertility, where its use is more controversial. Finally, we consider the benefits of future advancements in reproductive biology that may incorporate ICSI, such as in vitro spermatogenesis, neogametogenesis, and heritable genome editing. CONCLUSION: The versatility, consistency, and reliability of ICSI have made it the most prevalently utilized ART procedure worldwide.

Current evidence supporting a goal of singletons: a review of maternal and perinatal outcomes associated with twin versus singleton pregnancies after in vitro fertilization and intracytoplasmic sperm injection.

With increasing use of in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI) almost 2% of all babies born in the United States each year are now conceived with these technologies, making outcomes of IVF-ICSI extremely important not only to patients and families but to public health. Twin pregnancy rates after IVF-ICSI in the United States have declined since their peak in 2013 but remain at approximately 1 in 10 to 1 in 20 pregnancies. A review of the current international literature on twin versus singleton pregnancy outcomes after IVF-ICSI treatment confirms statistically significantly higher risks to maternal and perinatal health and statistically significantly higher health care costs. The field of infertility care should continue to work to develop practices that lower twin pregnancy rates to an absolute minimum to maximize the safety of these medical treatments.

Obstetric and perinatal outcomes of intracytoplasmic sperm injection versus conventional in vitro fertilization in couples with nonsevere male infertility.

OBJECTIVE: To determine whether intracytoplasmic sperm injection (ICSI) is associated with improved outcomes compared with conventional in vitro fertilization (IVF) for patients with nonsevere male factor infertility. DESIGN: Retrospective cohort. SETTING: University-affiliated reproductive endocrinology unit. PATIENT(S): Couples who received their first-cycle embryo transfer without severe oligoasthenozoospermia (OA) between January 2012 and December 2016 were included in this study. INTERVENTION(S): Six subgroup analyses were performed according to the proposed indications for the use of ICSI as follows: non-male factor infertility, advanced maternal age (≥38 years), unexplained infertility, low oocyte yield (≤6), mild OA, and moderate OA. MAIN OUTCOME MEASURE(S): Live birth rates and selected perinatal outcomes. RESULT(S): ICSI resulted in live birth rates similar to those achieved with IVF (41.68% vs. 44.31%). There were no significant differences in the incidences of gestational diabetes mellitus, hypertension disorder of pregnancy, placental previa, postpartum hemorrhage, cesarean delivery, fetal macrosomia, small for gestational age, large for gestational age, neonatal intensive care unit (NICU) admission, and congenital anomalies between the two groups. Subgroup analyses showed that ICSI resulted in a lower rate of NICU admission in couples with moderate OA. CONCLUSION(S): Our results suggested that routine use of ICSI for all causes of infertility did not result in better pregnancy and perinatal outcomes compared with conventional IVF in the first cycle. ICSI might be associated with a lower risk of NICU admission when used in couples with moderate OA. Large prospective studies are required to validate our current findings.

Artificial intelligence in the IVF laboratory: overview through the application of different types of algorithms for the classification of reproductive data.

Over the past years, the assisted reproductive technologies (ARTs) have been accompanied by constant innovations. For instance, intracytoplasmic sperm injection (ICSI), time-lapse monitoring of the embryonic morphokinetics, and PGS are innovative techniques that increased the success of the ART. In the same trend, the use of artificial intelligence (AI) techniques is being intensively researched whether in the embryo or spermatozoa selection. Despite several studies already published, the use of AI within assisted reproduction clinics is not yet a reality. This is largely due to the different AI techniques that are being proposed to be used in the daily routine of the clinics, which causes some uncertainty in their use. To shed light on this complex scenario, this review briefly describes some of the most frequently used AI algorithms, their functionalities, and their potential use. Several databases were analyzed in search of articles where applied artificial intelligence algorithms were used on reproductive data. Our focus was on the classification of embryonic cells and semen samples. Of a total of 124 articles analyzed, 32 were selected for this review. From the proposed algorithms, most have achieved a satisfactory precision, demonstrating the potential of a wide range of AI techniques. However, the evaluation of these studies suggests the need for more standardized research to validate the proposed models and their algorithms. Routine use of AI in assisted reproduction clinics is just a matter of time. However, the choice of AI technique to be used is supported by a better understanding of the principles subjacent to each technique, that is, its robustness, pros, and cons. We provide some current (although incipient) and potential uses of AI on the clinic routine, discussing how accurate and friendly it could be. Finally, we propose some standards for AI research on the selection of the embryo to be transferred and other future hints. For us, the imminence of its use is evident, providing a revolutionary milestone that will impact the ART.

ALWAYS ICSI? A SWOT analysis.

PURPOSE: Intracytroplasmatic sperm injection (ICSI) is a common procedure used to improve reproductive results, even among couples without male factor infertility. However, the evidence available is still uncertain on the possible advantages and deficiencies that this procedure may have in patients with no formal indication for ICSI. METHODS: A SWOT (strengths, weaknesses, opportunities, threats) analysis examines the possible advantages and deficiencies of performing ICSI in these patients with no formal indication. RESULTS: The evidence suggests that ICSI is not justified for non-male factor infertile couples requiring in vitro conception. One of the major strengths associated to the procedure is the virtual elimination of cases further complicated by total fertilization failure and a combination between IVF and ICSI on sibling oocytes has been advised in the literature. Greater technical difficulties, higher costs and performing an unnecessary invasive technique in some cases represent some of the weaknesses of the procedure, and questions regarding safety issues should not be ruled out. CONCLUSION: Despite the widespread use of ICSI in patients without a formal diagnosis of male factor infertility, evidence demonstrating its effectiveness in this population is still lacking. Additional large and well-designed randomized controlled trials are needed to clarify definitive indications for ICSI in non-male factor infertility.

ART strategies in Klinefelter syndrome.

PURPOSE: Patients with Klinefelter syndrome (KS) who receive assisted reproductive technology (ART) treatment often experience poor pregnancy rates due to decreased fertilization, cleavage, and implantation rates and even an increased miscarriage rate. Mounting evidence from recent studies has shown that various technological advances and approaches could facilitate the success of ART treatment for KS patients. In this review, we summarize the methods for guiding KS patients during ART and for developing optimal strategies for preserving fertility, improving pregnancy rate and live birth rate, and avoiding the birth of KS infants. METHODS: We searched PubMed and Google Scholar publications related to KS patients on topics of controlled ovarian stimulation protocols, sperm extraction, fertility preservation, gamete artificial activation, round spermatid injection (ROSI), and non-invasive prenatal screening (PGD) methods. RESULTS: This review outlines the different ovulation-inducing treatments for female partners according to the individual sperm status in the KS patient. We further summarize the methods of retrieving sperm, storing, and freezing rare sperm. We reviewed different methods of gamete artificial activation and discussed the feasibility of ROSI for sterile KS patients who absolutely lack sperm. The activation of eggs in the process of intracytoplasmic sperm injection and non-invasive PGD are urgently needed to prevent the birth of KS infants. CONCLUSION: The integrated strategies will pave the way for the establishment of ART treatment approaches and improve the clinical outcome for KS patients.

Endometrial thickness is associated with incidence of small-for-gestational-age infants in fresh in vitro fertilization-intracytoplasmic sperm injection and embryo transfer cycles.

OBJECTIVE: To investigate whether endometrial thickness (EMT) is associated with adverse obstetric and neonatal outcomes in fresh in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. DESIGN: Retrospective cohort study. SETTING: University-based reproductive medical center. PATIENT(S): Women under the age of 42 years who underwent IVF/ICSI treatment and received fresh ET in our unit from January 2017 to December 2018, resulting in a live singleton birth. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF/ICSI; fresh ET. MAIN OUTCOME MEASURE(S): Birth weight, gestational age, small for gestational age (SGA), large for gestational age (LGA), placenta previa, placental abruption, hypertensive disorders, and gestational diabetes mellitus. RESULT(S): The risk of being born SGA was statistically significantly increased in the EMT ≤7.5 mm group compared with those from the EMT >12 mm group (adjusted odds ratio [aOR] 2.391; 95% confidence interval [CI], 1.155-4.950). Moreover, maternal body mass index, secondary infertility, preterm delivery, and hypertensive disorders were all independent predictors for SGA. The mean birth weights of singletons in women with EMT ≤7.5 mm were lower than in the groups with EMT >7.5-12 mm and EMT >12 mm (3.25 ± 0.56 kg vs. 3.38 ± 0.51 kg and 3.39 ± 0.53 kg, respectively). CONCLUSION(S): After fresh IVF/ICSI-ET, the risk of SGA was increased twofold in women with EMT ≤7.5 mm compared with women with EMT >12 mm. We suggest that women with a thin EMT after obtaining a pregnancy by IVF should receive improved prenatal care to reduce the risk of delivering a SGA infant.

Factors Associated with Ovarian Hyperstimulation Syndrome (OHSS) Severity in Women With Polycystic Ovary Syndrome Undergoing IVF/ICSI.

Introduction: Age, polycystic ovary syndrome (PCOS), low body mass index (BMI), high antral follicle count (AFC), increased anti-Muller hormone (AMH) levels, and elevated serum estradiol (E2) concentrations are risk factors for ovarian hyperstimulation syndrome (OHSS). However, data on the relationship between risk factors and OHSS severity in patients with PCOS are rare. Objective: This retrospective study examined the risk factors for OHSS and their effect on OHSS severity in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Method: The records of 2,699 women were reviewed and included in this study. These women were diagnosed with PCOS during their first IVF/ICSI cycle between January 2010 and December 2017. We analyzed the association between each of the interrogated risk factors (including female age, BMI, AFC, basal serum E2, and the number of oocytes retrieved) and OHSS. The effects of each risk factor on OHSS severity were further explored. Logistic regression was performed as part of the above analysis. Results: Of the 2,699 women with PCOS who underwent assisted reproductive technology (ART), 75.2% had a normal response to controlled ovarian hyperstimulation (COH), while 24.8% developed OHSS. All OHSS patients were younger and had lower BMIs and basal serum follicle-stimulating hormone (FSH) and E2 levels but higher AFCs than those in the normal group. AFC demonstrated a strong correlation with OHSS, with a cutoff value of 24 in patients with PCOS. A total of 19.5% of the patients had mild OHSS, while 80.5% had moderate OHSS. Compared with those in the moderate OHSS group, those in the mild OHSS group were older and had higher basal serum FSH levels and lower serum E2 and T levels. However, BMI and AFC were not different between the mild and moderate OHSS groups. Basal serum E2 showed a strong correlation with OHSS severity, with a cutoff value of 37.94 pg/ml. Conclusions: AFC is a strong marker of OHSS, and basal serum E2 is the best predictor of OHSS severity in women with PCOS undergoing IVF treatment.