Twin pregnancies and perinatal outcomes: a comparison between fresh and frozen embryo transfer: a two-centre study.

RESEARCH QUESTION: To assess the perinatal and obstetric outcomes of twin pregnancies resulting from IVF frozen embryo transfer (FET) in comparison with fresh embryo transfer. DESIGN: A retrospective cohort study of 773 twin pregnancies conceived via IVF treatment. Data were collected from the records of two outpatient fertility IVF clinics of cycles conducted between 2006 and 2016. RESULTS: A total of 773 pregnancies were evaluated: 614 (79.4%) following FET and 159 (20.6%) following fresh embryo transfer. The FET group had a significantly higher mean birthweight (P = 0.002), and lower rates of small for gestational age (P = 0.003), low (P = 0.003) and very low birthweight (P = 0.006) infants. Also, a significantly lower rate of spontaneous second trimester miscarriage compared with the fresh embryo transfer group was observed (P = 0.001). No significant difference was found between groups regarding gestational age at delivery, term birth (after 37 weeks of gestation), twin discordancy rate, fetal major malformation rate, and hospitalization duration. CONCLUSION: In twin pregnancies, FET might have better perinatal outcomes compared with fresh embryo transfer in regards to birthweight and spontaneous second trimester miscarriages. Further research is needed to evaluate these results.

Repeated GnRH agonist doses for luteal support: a proof of concept.

RESEARCH QUESTION: What are the safety and feasibility of repeated subcutaneous doses of gonadotrophin-releasing hormone (GnRH) agonist for luteal support in IVF cycles triggered by a GnRH agonist? DESIGN: In this prospective trial, patients exhibiting oestradiol concentrations of over 2500 pg/ml after use of a GnRH agonist for triggering ovulation were initially randomized to GnRH agonist luteal support (0.1 mg subcutaneously every other day, starting on day 3 after embryo transfer) or to a control group supported by 80 µg of recombinant human chorionic gonadotrophin (HCG) on day 3 after embryo transfer. All patients underwent a day 5 blastocyst transfer. Randomization to the HCG luteal support was stopped owing to two cases of ovarian hyperstimulation syndrome (OHSS) and the study was continued solely with GnRH agonist luteal support. RESULTS: The study included 39 women in the repeated GnRH agonist luteal support group and seven in the HCG micro dose group. There were no cases of OHSS among patients supported by a GnRH agonist, and no other adverse events were recorded. There were no cases of bleeding before the pregnancy test, and hence no cases of an insufficient luteal phase. A clinical pregnancy rate of 43.6% was achieved with GnRH agonist luteal support. Hormone dynamics during the stimulation cycle reflected rising LH and progesterone concentrations after the introduction of GnRH agonist support. CONCLUSIONS: Repeated doses of GnRH agonist every other day as a method of luteal support provided safe and effective luteal support for women who underwent GnRH agonist triggering in a GnRH antagonist IVF cycle.

Does stress affect IVF outcomes? A prospective study of physiological and psychological stress in women undergoing IVF.

RESEARCH QUESTION: What are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF? DESIGN: A prospective cohort study of 72 patients undergoing IVF in 2017 and 2018. Physiological stress was assessed by salivary cortisol measurements: (i) pretreatment, when the patient received the IVF protocol; (ii) before oocyte retrieval (follicular cortisol was also measured); and (iii) before embryo transfer. Emotional stress was evaluated at each assessment with the State-Trait Anxiety Inventory and a 1-10 Visual Analogue Scale (VAS, referred to as the 'Stress Scale'. Correlations between cortisol concentrations, psychological stress and IVF outcome were assessed. RESULTS: Salivary cortisol concentrations increased by 28% from pretreatment phase (0.46 ± 0.28 µg/dl) to maximum concentration on oocyte retrieval day (0.59 ± 0.29 µg/dl, P = 0.029) and then decreased by 29% on embryo transfer day (0.42 ± 0.23 µg/dl, P = 0.0162). On embryo transfer day, cortisol among women in their first cycle was higher than women who underwent more than one treatment (P = 0.024). Stress Scale score increased by 39% from pretreatment to a maximum score on oocyte retrieval day and then decreased by 12% on embryo transfer day. Salivary cortisol and Stress Scale were not related to subsequent embryo transfer, fertilization rate, embryo quality or clinical pregnancy rate. Follicular cortisol concentration was positively correlated with fertilization rate (r = 0.4, P = 0.004). CONCLUSION: It can be cautiously concluded that physiological and psychological stress do not negatively affect IVF outcomes. Moreover, high follicular cortisol concentrations might have positive effects on pregnancy rates.

Adverse pregnancy outcomes and multiple nuchal cord loops.

PURPOSE: To evaluate the effects of nuchal cord and the number of loops during labor and delivery on delivery outcomes among women with singleton pregnancy who delivered vaginally. METHODS: This retrospective cohort study included 42,798 women with singleton, vertex, and vaginal deliveries at 24-43 weeks of gestation. We analyzed delivery outcomes based on the number of nuchal cord loops. RESULTS: A total of 42,798 deliveries met the inclusion criteria, of which, 3809 (8.9%) had nuchal cord with 1 loop at delivery, 1035 (2.42%) had 2 loops, and 258 (0.6%) had 3 loops. Nuchal cord with 3 loops compared to no nuchal cord has been associated with higher incidence of intrauterine fetal death (1.9%), Apgar scores less than 7 at 1 and 5 min (7.4%, 2.3%), and higher rate of operative vaginal deliveries (17.5%). Nuchal cord with 2 or 3 loops was associated with higher incidence of intrauterine growth restriction (10.2%, 11.6%).  In a multiple logistic regression model, nuchal cord with 3 loops was an independent risk factor for operative vaginal delivery and Apgar score less than 7 in 1 min. CONCLUSIONS: In the case of vaginal delivery in the presence of nuchal cord, as the number of nuchal cord loops increased, so did the number of adverse delivery outcomes. While 3 loops were associated with higher incidence of intrauterine fetal death, intrauterine growth restriction, increased operative vaginal deliveries, and low Apgar scores, 1 loop was not associated with adverse perinatal outcomes.

Macrolide antibiotics roxithromycin vs. azithromycin for preterm premature rupture of membranes: a retrospective comparison.

PURPOSE: Prophylactic antibiotics to prolong latency and reduce the risk of neonatal and maternal infections are used for preterm premature rupture of membranes. This study compared outcomes between two macrolides: roxithromycin given twice a day for a week and azithromycin, given as a single dose, which is more convenient. METHODS: Two local protocols were retrospectively compared: roxithromycin and ampicillin from July 2005 to May 2016, and azithromycin and ampicillin from May 2016 to May 2018. Inclusion criteria were singleton pregnancy, at 24-34 weeks of gestation upon admission with preterm premature rupture of membranes. Primary outcome was length of the latency period, defined as time from first antibiotic dose to 34 + 0 weeks, or spontaneous or indicated delivery prior to 34 + 0 weeks. Secondary outcomes were rates of chorioamnionitis, delivery mode, birth weight and Apgar scores. RESULTS: A total of 207 women met inclusion criteria, of whom, 173 received penicillin and roxithromycin and 34 received penicillin and azithromycin. Baseline characteristics were similar between groups. The latent period was longer in the azithromycin group than in the roxithromycin group (14.09 ± 14.2 days and 7.87 ± 10.2 days, respectively, P = 0.003). Rates of chorioamnionitis, cesarean deliveries, Apgar scores and birth weights were similar between the groups. CONCLUSIONS: Azithromycin compared to roxithromycin results in a longer latency period in the setting of preterm premature rupture of membranes at 24-34 weeks of gestation. Given its more convenient regimen and our results, it seems justified to use azithromycin as the first-line treatment for patients with preterm premature rupture of membranes.

Does music during labor affect mode of delivery in first labor after epidural anesthesia? A prospective study.

KEY MESSAGE: Listening to music during labor increases the likelihood that primiparas will have a spontaneous vaginal delivery. PURPOSE: To examine the effects of exposure to music during labor on the mode of delivery and parturients' stress levels. METHODS: This prospective, interventional study included 124 low-risk women who were recruited during latent phase of their first labor after epidural anesthesia. Patients were grouped according to their preference to receive music intervention or not. The music intervention included two subgroups: soft classical music and rhythmic music. We evaluated cortisol levels in saliva as a surrogate for stress level and State-Trait Personality Inventory at enrollment and 1-3 h later in all women who were still in labor. Delivery and perinatal outcomes were collected from electronic medical records. Correlations between the music intervention and maternal and perinatal outcomes were evaluated. RESULTS: Spontaneous vaginal delivery was significantly more frequent among women listening to music compared to the non-music group (P = 0.035). A trend towards lower rates of cesarean delivery was noted in the music group (P = 0.08), with no difference in instrumental vaginal delivery rates. Stress levels, as measured by questionnaires and by cortisol levels, blood pressure and pulse rate, remained similar throughout the study. No differences were noted between the different genres of music when examining obstetric and perinatal outcomes and stress levels. CONCLUSION: Listening to music during labor, improves the likelihood of primiparas to have a vaginal delivery regardless of stress level. As this treatment is simple, easy, and harmless to administer, we suggest it may be offered to all patients during labor.

A novel solution for freezing small numbers of spermatozoa using a sperm vitrification device.

STUDY QUESTION: Does a novel sperm vitrification device (SpermVD) provide an efficient method for freezing a small number of human spermatozoa from men suffering from non-obstructive azoospermia? SUMMARY ANSWER: The novel SpermVD is an efficient and simple carrier method for freezing a small number of spermatozoa in low-volume droplets, reducing post-thaw search time from hours to minutes, allowing a 96% recovery rate and leading to successful use of sperm for fertilization. WHAT IS KNOWN ALREADY: Previous methods for cryopreservation of small numbers of human spermatozoa (e.g. mini-straws, ICSI pipette, alginate beads, cryoloop) have been proposed as a solution for cases of severe male infertility. Many drawbacks have prevented their widespread use, including cumbersome preparation and sperm retrieval procedures, and the fact that the thawed spermatozoa are not immediately available for micromanipulation and required additional treatment which posed excess risk of harm. STUDY DESIGN, SIZE, DURATION: We conducted a feasibility experiment of the novel SpermVD and a prospective cohort study of ICSI cycles in men suffering from non-obstructive azoospermia in two outpatient fertility IVF clinics, from 2015 through 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent extended ejaculate search prior to the day of oocyte retrieval, and any single motile spermatozoa found was transferred to 0.8 µl droplets of 1:1 washing medium/cryoprotectant on the SpermVD, then plunged into liquid nitrogen for cryopreservation. In patients with non-obstructive azoospermia who underwent surgical TESE, both the motile and immotile spermatozoa found underwent cryopreservation using the SpermVD. On the day of oocyte retrieval, the SpermVD was thawed, directly transfered to the ICSI plate and retrieved spermatozoa were used for the ICSI procedure. MAIN RESULTS AND THE ROLE OF CHANCE: The prospective cohort included 44 cases. We used the SpermVD to vitrify 631 spermatozoa, of which 540 (86%) were motile. The average number of frozen spermatozoa per patient was 14.3 ± 9.3. After thawing, we retrieved 607 spermatozoa, producing a recovery rate of 96%. The average number of thawed spermatozoa was 13.8 ± 9.2. The recovery of 180 thawed motile sperm accounted for 33% of all frozen motile spermatozoa. The fertilization rate was 59%. Of 44 oocyte retrieval procedures, 24 (55%) clinical pregnancies were achieved. The delivery rate (not including three ongoing pregnancies) was 32% and the miscarriage rate was 29%. LIMITATIONS, REASONS FOR CAUTION: Although we presented the SpermVD on 44 cases, a larger cohort would provide more information. Moreover, we cryopreserved only motile sperm from the ejaculates and not immotile sperm, thus limiting the knowledge regarding the efficacy of the VD for immotile sperm from this source. WIDER IMPLICATIONS OF THE FINDINGS: The novel SpermVD is a simple efficient carrier, optimizing the protocol for freezing a small number of spermatozoa. It may allow for the routine use of frozen spermatozoa after TESE for men suffering from non-obstructive azoospermia and thus avoid repeated TESE surgeries. Furthermore, in cases of non-obstructive azoospermia, routine cryopreservation of the retrieved spermatozoa prior to the IVF cycle may avoid the risk of cycle cancelation and thus decrease the number of unnecessary oocyte retrieval procedures. STUDY FUNDING/COMPETING INTEREST(S): There was no external funding. There are no competing interests. TRIAL REGISTRATION NUMBER: IRB no 00119-16-ASMC.

The significance of human spermatozoa vacuoles can be elucidated by a novel procedure of array comparative genomic hybridization.

STUDY QUESTION: Is there an association between spermatozoon genomic stability and vacuolar morphology and location? SUMMARY ANSWER: The genomic stability of spermatozoa is associated with specific characteristics of vacuolar morphology (depth) and location (cellular compartment, i.e. nucleus and equatorial region). WHAT IS KNOWN ALREADY: Genetic anomalies in sperm are correlated with semen abnormalities, yet the advantage of morphologically based selection of spermatozoa for IVF according to current criteria is controversial. Selection criteria based on the number of vacuoles and their size have been proposed and are widely applied. Nevertheless, it has not improved the ICSI success rates, suggesting the currently used vacuole criteria are incomplete. STUDY DESIGN, SIZE, DURATION: Normal sperm according to Motile Sperm Organelle Morphology Examination criteria (MSOME) and common vacuole grading were evaluated. An additional evaluation of sperm vacuole morphology according to novel vacuole criteria (i.e. location and depth) was conducted. An assessment to align these specific vacuolar morphology features with genomic stability was conducted among spermatozoa from infertile patients and healthy fertile donors aged 24-38 between June 2015 and July 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Single spermatozoa (n = 53) from 16 infertile patients and 14 fertile donors were morphologically and genetically evaluated. Each spermatozoon was examined morphologically, by ultra-magnification ×6300, and genetically by a novel comparative genomic hybridization protocol, without the use of reference DNA, to assess chromosomal instability as evident by copy number variations (CNV). MAIN RESULTS AND THE ROLE OF CHANCE: We established an association between genomic stability and vacuolar morphology as a base for a new classification according to novel vacuolar criteria, specifically depth and location. Genomic instability was found to be related to these two main features of vacuoles and, surprisingly not to the number and size of vacuoles as in the previously proposed classifications. High CNV spermatozoa were characterized by vacuoles located in the nucleus and/or equatorial segment or by deep vacuoles, while, low CNV spermatozoa were characterized by a complete lack of vacuoles or non-deep vacuoles not located in the nucleus/equatorial segment. A putative threshold of ~265 CNV was deduced to distinguish between genetically stable and unstable spermatozoa, and 94% of the tested spermatozoa segregated accordingly. LIMITATIONS REASONS FOR CAUTION: A relatively small sample of spermatozoa were examined-53 in total. However, the association between vacuoles location and morphology and genomic stability was significant. This is the first study evaluating spermatozoon genomic stability with respect to vacuole morphology according to novel vacuole criteria (i.e. location and depth) and further investigation is warranted to verify the value of these criteria in larger sample size clinical studies. WIDER IMPLICATIONS OF THE FINDINGS: Our results, which are based on spermatozoon vacuoles morphological classification and genomic parameters, indicate an association between vacuoles morphology and location and genomic stability. The data presented herein suggest the existence of subpopulations of spermatozoa potentially appropriate for IVF-ICSI, as they appear normal according to the current MSOME and vacuoles classification, however they are almost certainly genetically damaged. As current criteria have yet to achieve an unequivocal evaluation of the implantation potential of a given spermatozoon, we propose novel criteria, based on specific vacuolar morphological traits; depth and location, as these were found aligned with genomic findings. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Time lapse microscopy is useful for elective single-embryo transfer.

The aim of our study was to evaluate time lapse microscopy (TLM) as a selection tool for single-embryo transfer (SET) on day 5, blastocyst stage. An observational cohort study was conducted. Patients who had SET were compared to patients who had double embryo transfer (DET). A total of 108 patients were included in analysis, 83 had SET, and 25 underwent DET. Embryos were incubated and evaluated using TLM. The pregnancy rates were similar between the groups (42.2% in SET and 48.0% in DET). However, the multiple pregnancy rate was significantly higher in the DET group compared to the SET group (41.7% versus 2.9%, respectively; p < 0.001). This study concludes that SET with TLM do not decrease pregnancy rates compared to DET. However, transfers of two embryos increase the rate of multiple pregnancies.

Fertility treatment and dichorionic discordant twins - are they related?

OBJECTIVE: This prospective cohort study evaluated the relationship between fertility treatments and the prevalence and outcomes of dichorionic discordant twins. This issue has gained importance due to twin gestations resulting from fertility treatments. STUDY DESIGN: Mothers of dichorionic twin pregnancies achieved in a single fertility clinic by assisted reproduction techniques, who had completed the first trimester of the pregnancy, were prospectively enrolled. Pregnancies with major fetal anomalies were excluded. Data regarding concordant and discordant twins based on the fertility treatments given to achieve the pregnancies were analyzed to determine the prevalence of discordance and pregnancy outcomes. RESULTS: A total of 571 dichorionic twin pregnancies were available for evaluation. Fertility treatments modalities, sperm quality and implantation of cultured and thawed embryos did not influence the rate and severity of discordant twins. Increased hospitalization rates were found among discordant (n=108) compared to concordant (n=463) twins (47.2% vs. 31.3%, P<0.0001) and higher rates of betamethasone treatment (65.7% vs. 28.9%, P<0.0001). Secondary analysis of discordant pregnancies with a growth restricted twin, revealed the same results. We found no association between various fertility treatments and twin discordance. CONCLUSIONS: Our data suggest that fertility treatments do not play a major role in the pervasiveness and outcome of discordant twin pregnancies.

Is the ratio of maternal serum to amniotic fluid AFP superior to serum levels as a predictor of pregnancy complications?

PURPOSE: The use of maternal serum alpha fetoprotein (MSAFP) levels as a predictor of pregnancy complications (PC) is well established. We hypothesized that the ratio between the MSAFP/AFAFP levels (RATIO) will more accurately predict PC than MSAFP levels alone. METHODS: Women who had a MSAFP test followed by amniocentesis were divided into two groups: those who had PC comprised the study group and those who had an uneventful pregnancy served as the control group. Data regarding pregnancy and delivery course were collected. The RATIO between the study and the control groups was compared. RESULTS: 166 women were included in the study, of which 24 had PC. A significant correlation was found between the RATIO and intrauterine growth restriction (IUGR) and week of delivery. Six pregnancies had elevated MSAFP levels; two with RATIO below 2 had uneventful pregnancies. Among the other four pregnancies with RATIO above two, one had IUGR and the other, placental abruption. CONCLUSION: Our data suggest that the RATIO might serve as a predictor of IUGR and week of delivery. Although the number of patients in the current study was relatively small, the novelty of the proposed simple marker implies that a larger scale study is warranted. Such studies may confirm this finding and a possible advantage of using this RATIO instead of or in addition to MSAFP values for better prediction of pregnancies at risk for PC.

What are the best predictors for successful GnRH antagonist protocol in in vitro fertilization (IVF) treatment?

OBJECTIVE: To determine factors that affect the success rate of GnRH antagonist protocol in in vitro fertilization (IVF) treatment. DESIGN: Retrospective cohort study. PATIENTS: Patients who underwent IVF cycle with their first GnRH antagonist protocol. INTERVENTION: Antagonist protocol during IVF treatment. The main outcome measurements were; Number of retrieved oocytes, embryo quality and pregnancy rate. RESULTS: Gravidity was negatively correlated with number of eggs (p = 0.017), while total follicle number ≥15 (p = 0.044) and E(2) on day of human chorionic gonadotropin (HCG) (p = 0.000) had a positive correlation with number of eggs. Maximum follicle size at HCG administration showed a trend toward an inverse correlation (p = 0.053). Addition of LH to drug stimulation was negatively correlated with number of eggs in comparison to rFSH only (p = 0.013 and 0.0000, respectively). Age and number of frozen eggs were negatively correlated with successful pregnancy (p = 0.025 and 0.004, respectively), while embryo quality, gravidity and number of embryos were positive (p = 0.011 and 0.014, respectively). CONCLUSION: Controlled parameters like timing of antagonist start, duration of antagonist and the optimal leading follicle diameter for HCG triggering had no effect on treatment outcomes.

Clinical pregnancy rates among anovulatory and oligoovulatory women after letrozole versus hormone replacement therapy in frozen-thawed embryo transfer cycles.

This cohort study investigated whether letrozole versus hormone replacement therapy (HRT) results in higher live birth rate among anovulatory and oligoovulatory women in frozen-thawed embryo transfer (FET) cycles. It was conducted from 1st February 2018 to 31st January 2019 and included 261 anovulatory and oligoovulatory women. Since letrozole has become an effective alternative to HRT cycles, 121 patients received letrozole in 121 cycles from 1st February 2018 to 31st January 2019 and were compared to 140 HRT FET cycles among 140 women from 1st February 2017 to 31st January 2018. The primary outcome was live birth rate. Secondary outcomes were clinical pregnancy, multiple pregnancy and miscarriage rates. Clinical pregnancy and live birth rates of transferred cleavage embryos were higher in the letrozole compared to the HRT group (36/65 (55.3%) vs. 20/110 (18.1%), p < 0.001) and (25/65 (38.4%) vs. 17/110 (15.4%), p < 0.001) respectively, whilst these rates were similar for transferred blastocyst embryos. Miscarriage and multiple pregnancy rates were similar between groups. The letrozole group was older than the HRT group (31.8 ± 5.1 vs. 29.9 ± 5.1 years, p = 0.002) and more smoked cigarettes (p = 0.035). Groups were similar regarding BMI, male versus non-male indication for fertility treatment, peak oestradiol levels, and numbers of oocytes retrieved, blastocysts, frozen and transferred embryos. Letrozole compared to HRT might improve live birth and clinical pregnancy rates among anovulatory and oligoovulatory women undergoing FET cycles.

Monitoring stimulated cycles during in vitro fertilization treatment with ultrasound only--preliminary results.

OBJECTIVE: To evaluate if monitoring patients by ultrasound (US) only during in vitro fertilization (IVF) treatment is safe. DESIGN: Randomized prospective study. INTERVENTION: Patients undergoing their first IVF treatment were randomized into two groups. The ultrasound only group (study group) was monitored by US for follicle size and endometrial thickness without blood tests. In this group, only one blood test was taken before human chorionic gonadotropin (hCG) injection, to ensure a safe level of estradiol (E(2)) regarding ovarian hyperstimulation syndrome (OHSS) risk. The control group was monitored by ultrasound plus serum estradiol and progesterone concentration at each visit. MAIN OUTCOME MEASURE: Clinical pregnancy rate. RESULTS: No differences were found between the groups in the parameters of IVF treatment, induction days, number of ampoules, E(2) level of hCG, as well as embryo quality. The clinical pregnancy rate was not statistically different between the groups, 57.5% vs. 40.0%, respectively (p = 0.25). No OHSS cases were found among the study or control groups. CONCLUSION: Ultrasound as a single monitoring tool for IVF cycles is reliable, safe, patient friendly, and reduces treatment expenses. In an era of cost effectiveness awareness, this regimen should be considered for routine management in IVF programs.

Physiological and psychological stress responses to labor and delivery during COVID-19 pandemic: a cohort study.

OBJECTIVE: To evaluate objective (saliva cortisol) and subjective (questionnaire) stress levels during the Coronavirus disease (COVID-19) pandemic compared to before the pandemic and their effects on obstetric and neonatal outcomes. METHODS: This cohort study included 36 women with low-risk, singleton, term deliveries at a tertiary academic center during the COVID-19 pandemic and 49 who delivered before. Physiological stress was evaluated with salivary cortisol measurements, and emotional stress with stress scale questionnaires (0-10) during active and full dilation stages of labor, and 2-min postpartum. Cord blood cortisol and pH were obtained. Delivery mode, complications, and neonatal outcomes were evaluated. RESULTS: Psychological stress was higher for the COVID-19 group compared to controls during full dilation (6.2 ± 3.4 vs. 4.2 ± 3, p = .009). The COVID-19 group had significantly lower cord cortisol levels (7.3 vs. 13.6 mcg/dl, p = .001). No differences were found regarding salivary cortisol level assessments at active, full dilation and 2-min post-delivery (p = .584, p = .254, p = .829, respectively). No differences were found regarding pH < 7.1 (p = .487), 1- and 5-min Apgar scores < 7 (p = .179) and neonatal weight (p = .958). CONCLUSIONS: Women who delivered during COVID-19 pandemic had higher stress levels at full dilation and lower cord cortisol levels, as may be expected after exposure to a chronic stressor.

The possibility of integrating motile sperm organelle morphology examination (MSOME) with intracytoplasmic morphologically-selected sperm injection (IMSI) when treating couples with unexplained infertility.

PURPOSE: To examine the efficacy of motile sperm organelle morphology examination (MSOME) and intracytoplasmic morphologically-selected sperm injection (IMSI) for unexplained infertility. METHODS: This historical study, included 271 couples with primary, unexplained infertility/male subfertility, treated at an outpatient, IVF clinic, 2015-2018. These couples underwent MSOME after ≥3 failed intrauterine insemination (IUI) cycles and ≥1 failed IVF-ICSI cycle. They proceeded to intracytoplasmic morphologically-selected sperm injection (IMSI) within 6 months of MSOME. IMSI is conducted on the day of oocyte pick-up with a fresh semen sample. Pregnancy and delivery rates were analyzed. RESULTS: The cohort was divided based on percentage of normal cells at MSOME: Group A included 55 with no normal cells, Group B, 184 with 0.5%≤ normal cells ≤1.5% and Group C, 32 with ≥2% normal cells. Normal spermatozoa were found in 49 (89%) of Group A after extensive search. Group A had higher pregnancy rate (62.7%) compared to B (47.2%, P = 0.05) and C (28.1%, P = 0.002). Group B had higher pregnancy rate than C (p = 0.045). Delivery rate was higher in Group A (52.1%) compared to B (34.1%, p = 0.023) and C (21.9%, p = 0.007). Pregnancy and delivery rates were higher in A compared to B+C (p = 0.018, p = 0.01, respectively). CONCLUSIONS: MSOME may be useful for evaluating unexplained infertility. IMSI can be recommended for men with <2% normal spermatozoa at MSOME.

Optimizing the protocol for vitrification of individual spermatozoa by adjusting equilibration time.

Efficient cryopreservation of small numbers of human spermatozoa is essential in cases of severe male infertility, especially those requiring surgical sperm retrieval. Although vitrifying individual spermatozoa on sperm vitrification devices (SpermVD®) provided optimal cell retrieval upon warming, motility rates tended to be lower than with bulk-freezing. Post-warming motility is directly affected by cryoprotectant exposure; however, optimal cryoprotectant equilibration time is unknown. We evaluated several timeframes exposing individual spermatozoa to cryoprotectant before freezing and different cryoprotectants. A total of 2,925 spermatozoa from 20 patients ranging from normozoospermic to moderate oligoteratoasthenozoospermic were vitrified in small groups, on 60 SpermVD®, in 1 µl droplets of 1:1 v/v cryoprotectant/washing medium mixture. Each group was vitrified after 2-60 minutes equilibration time. Motility of each group was evaluated after warming. Leftover pellets were frozen in cryotubes in a mixture of 1:1 v/v cryoprotectant/washing medium after 10 minutes equilibration at room temperature and 10 minutes on liquid nitrogen vapors. Post-thaw motility correlated negatively with cryoprotectant exposure time. The highest post-warming motility rate (32.1%) was observed with 8-minutes equilibration. After 10 minutes, motility rate of vitrified sperm was lower than that of bulk-freezing (31.7% vs. 37.0%, p < 0.0001). Different cryoprotectants did not affect the results. Therefore, for vitrifying small numbers of spermatozoa, we suggest maximum equilibration time of 8-minutes to achieve maximum motility after warming.

Can we predict the need for antihypertensive treatment during the early postpartum period for women with preeclampsia or gestational hypertension?

OBJECTIVES: To determine factors that predict the need for antihypertensive treatment during early postpartum period among women with preeclampsia or gestational hypertension. STUDY DESIGN: Retrospective cohort of 358 women. MAIN OUTCOME MEASURES: Demographic, clinical and laboratory data of 63 women diagnosed with preeclampsia or gestational hypertension during a singleton pregnancy and who needed antihypertensive agents during early postpartum period were compared to 295 who did not. RESULTS: No difference was found between groups regarding age, parity, body mass index, or weight gain (p = 0.95, 0.19, 0.56, and 0.078, respectively). Early onset preeclampsia or gestational hypertension was diagnosed among 28.6% of the women who subsequently needed antihypertensive treatment, as compared to 4.1% who did not (p < 0.001). Antepartum, mean maximum blood pressure in the treated vs. untreated group was 165/109 mmHg vs. 150/100 mmHg, respectively (p = 0.001). Groups did not differ regarding symptoms of preeclampsia (38.7% vs. 31.5%, p = 0.273) or laboratory abnormalities. The group that received antihypertensive treatment during early postpartum period, had more preterm deliveries (p < 0.001) and Cesarean deliveries (p < 0.001), and more received magnesium sulfate during labor (p < 0.001). During the early postpartum period, mean maximum blood pressure was higher among the treated group (167/106 vs. 143/92, p = 0.001), as were symptoms of preeclampsia (p = 0.001). The groups were similar regarding laboratory abnormalities that define preeclampsia. CONCLUSIONS: Early onset preeclampsia or gestational hypertension, severe antepartum hypertension, magnesium sulfate during labor, preterm, and Cesarean delivery might be good predictors of the need for antihypertensive treatment during early postpartum period.

Fertility outcomes after extended searches for ejaculated spermatozoa in men with virtual azoospermia.

OBJECTIVE: To assess the fertility outcomes of extended searches for ejaculated spermatozoa in men with virtual azoospermia. DESIGN: A retrospective cohort of 242 couples whose male partner suffered from nonobstructive azoospermia and who were treated with the use of intracytoplasmic sperm injection (ICSI). SETTING: Not applicable. PATIENT(S): One hundred forty patients were referred to an extended search in the ejaculate and 102 patients were referred to microsurgical testicular sperm extraction (microTESE). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of sperm retrieval, fertilization, and pregnancy, take-home baby rate, and missed abortion rate were analyzed and compared. RESULT(S): In the ejaculated spermatozoa group, motile spermatozoa were retrieved in 91 cases (65%) and on oocyte pick-up day in 71 cases (78%), compared with 70 cases (68%) in the microTESE group, with a similar incidence of sperm retrieval between groups. No significant difference was found between groups regarding mean number of embryo transfer and fertilization and pregnancy rates. There was no significant difference between groups regarding take-home baby rate. A significantly higher first-trimester missed abortion rate was found in the ejaculated sperm group (n = 14; 52%) compared with the microTESE group (n = 3; 8.6%). CONCLUSION(S): Conducting an extended spermatozoa search in the ejaculate of men with virtual azoospermia can provide pregnancy rates similar to those obtained with the use of microTESE, with a higher rate of spontaneous abortions in the ejaculate group.