Effect of Male Cigarette Smoking on In Vitro Fertilization (IVF) Outcomes and Embryo Morphokinetic Parameters.

This retrospective cohort study examines the association between male smoking status and embryo development in vitro. The study included non-smoking women aged under 40 years who underwent in vitro fertilization (IVF) at Yanaihara Women's Clinic from May 2019 to May 2022, and they were divided into two groups according to the husband's smoking status. The effect of male smoking status on IVF outcomes was compared retrospectively based on embryonic development using a time-lapse incubator. A total of 184 patients were included; 272 oocytes of 45 female non-smokers were cultured with the sperm of male smokers, and 816 oocytes of 139 female non-smokers were cultured with the sperm of male non-smokers. No significant differences were observed between male smokers and non-smokers groups with regard to fertilization and the top-quality embryo on day 3 and day 5 (p > 0.05). The male smoker group's embryos reached the early cleavage-stage parameters (time of pronuclei appearance to the five-cell stage) significantly earlier than the male non-smoker group's embryos (p < 0.05). However, no significant differences were observed between the two groups in other parameters of top-quality blastocysts (p > 0.05). It was concluded that male smoking has some differences on the timing of early embryonic events on time-lapse examination.

Efficacy of Hyaluronan-Enriched Transfer Medium for Low-Grade Frozen Embryo Transfer.

RESEARCH QUESTION: This study aimed to retrospectively evaluate the efficacy of a hyaluronan-enriched transfer medium (HETM) for transfer failures and transfer of frozen embryos that have been graded as C at the time of transfer according to the Gardner classification of trophectoderm (TE). DESIGN: This study included 365 cycles of unsuccessful frozen-thawed embryo transfers in hormone replacement cycles graded C according to the Gardner classification of TE at the time of transfer. Clinical pregnancy rates were compared using the χ2 test, with the patients divided into two groups: one whose transfers did include HETM (HETM group) and one whose transfers did not include HETM (control group). As a subgroup analysis, patients with a TE grade of C at the time of transplantation were divided into two groups: those aged 39 years or younger and those aged 40 years or older at the time of transplantation. The clinical pregnancy rates of the groups with and without HETM were then compared. RESULTS: No difference in the clinical pregnancy rates between the HETM and control groups was observed. CONCLUSIONS: Hyaluronic acid is believed to favor implantation by promoting adhesion between the embryo and the endometrium, and there are reports of improved implantation and pregnancy rates as a result of HETM. However, the present results suggest limited effectiveness for HETM. Further case series should be conducted, and the suitability of its use as a treatment should be investigated.

First birth following assisted sperm fusion insemination using sperm bound to zona pellucida.

PURPOSE: To report a live birth after transfer of a vitrified-warmed blastocyst produced by assisted sperm fusion insemination (ASFI). METHODS: Oocyte retrieval and in vitro fertilization (IVF) were performed on a 37-year-old woman. Six hours after IVF, an oocyte exhibited a single polar body and so was defined as an unfertilized oocyte. A motile sperm was collected from the zona pellucida of the unfertilized oocyte by an injection needle. The motile sperm was pressed onto the membrane of the unfertilized oocyte. RESULTS: Two oocytes were matured and subjected to IVF. One of the 2 oocytes exhibited only one polar body and was defined as an unfertilized oocyte at 6 h after IVF; this oocyte then was subjected to ASFI. Two pronuclei were observed on the next day and cultured to the blastocyst stage. This embryo achieved blastocyst status and was vitrified on day 5. The resulting vitrified-warmed blastocyst was transferred, resulting in pregnancy and subsequent delivery of a healthy boy. CONCLUSION: This report describes the first case of a successful birth following transfer of a vitrified-warmed blastocyst produced by ASFI.

Fertilization with human sperm bound to zona pellucida by pressing onto the oocyte membrane.

This study aimed to determine whether fertilization can be obtained by assisted fusion of oocyte and sperm without breaking the oocyte membrane. A total of 79 infertile couples, each with at least one unfertilized oocyte after in vitro fertilization (IVF), were recruited. Sperm collected from the zona pellucida (ZP) were pressed onto the membrane of unfertilized oocytes at either 6 h or 24 h after IVF, a procedure that we designated as assisted sperm fusion insemination (ASFI). The results of ASFI were compared with those obtained in a previous trial on oocytes in which rescue intracytoplasmic sperm injection (ICSI) was performed at 6 h after IVF. Acrosome reaction (AR) rate of sperm bound to ZP, fertilization rate, degeneration rate, and blastocyst formation rate were evaluated. The AR rate of sperm collected from the ZP was significantly higher than that of the motile sperm recovered from around the oocytes but not bound to the ZP after IVF (98.0% vs. 28.6%). ASFI which was performed at 6 h after IVF yielded a mean fertilization rate of 73.4% (58/79), a degeneration rate of 0% (0/79) and a blastocyst formation rate of 60.8% (31/51). Rescue ICSI which was performed at 6 h after IVF yielded a mean fertilization rate of 70.0% (70/100), a degeneration rate of 4% (4/100) and a blastocyst formation rate of 42.4% (25/59). Binding of sperm to the ZP typically results in AR. ASFI with acrosome-reacted sperm collected from the ZP yielded the fertilization rates similar to those obtained with rescue ICSI.

Morphologically poor blastocysts could affect the implantation rate of a morphologically good blastocyst during a double-blastocyst transfer for patients who have experienced repeated implantation failures.

PURPOSE: Increasing the number of transferred blastocysts sometimes is selected for patients with repeated implantation failure (RIF). To confirm this strategy, the pregnancy rates (PRs) were compared among the groups who had transferred either a single morphologically good blastocyst (MGB group), double blastocysts with both a MGB and a morphologically poor blastocyst (MGB + MPB group), or a double-BT with 2 MGBs (two-MGB group). METHODS: This study was performed between April, 2009 and September, 2014, including 634 cycles for 354 patients with RIF. All the patients received cryopreserved blastocysts in either hormone replacement or natural ovulatory cycles. The included MGBs were at more than the Gardner grade 3BB stage. The PR and implantation rates (IRs) among the three groups were statistically evaluated by the chi-square test. Statistical significance was set at P < .01. RESULTS: Although the PRs were similar in these three groups, the IR in the MGB + MPB group was significantly lower than that of the MGB group. The rate in the two-MGB group also was significantly lower than that of the MGB group. CONCLUSION: A double-BT with a MGB and a MPB does not increase the pregnancy rate, compared with a single-BT with a MGB among patients with RIF.

Difference in the size of the placenta and umbilical cord between women with natural pregnancy and those with IVF pregnancy.

PURPOSE: The purpose of this study was to compare the sizes of the placenta and umbilical cord in women with natural pregnancy versus those undergoing in vitro fertilization (IVF). METHODS: Overall, 1610 cases of uncomplicated single pregnancies with vaginal delivery at ≥ 37 weeks of gestation were included in this study. The patients were divided into two groups: natural pregnancy group (n = 1453) and IVF pregnancy not including intracytoplasmic sperm injection (ICSI) treatment (n = 157). The groups were compared in terms of gestational week, maternal age, parity, maternal weight gain, prepregnancy maternal BMI, infant weight at birth, infant head circumference, placental weight, cross section of the placenta, cross section of the umbilical cord, insertion site of the umbilical cord, and umbilical cord length. Stepwise selection and multivariate logistic regression were used for statistical analysis to correct the result as an independent factor. RESULTS: There was no difference in the size of the placenta and umbilical cord between women with natural pregnancy and with IVF, but the incidence of velamentous insertion of the cord was significantly increased in women with IVF pregnancy (adjusted odd ratio [AOR] 1.72, 95% confidence interval [CI] 1.08-2.72, p = 0.026). CONCLUSIONS: Although there is no difference in placental weight and cord size, velamentous insertion of the umbilical cord increases in IVF pregnancy and needs careful observation during the delivery process.

Dichorionic triplets following frozen-thawed poor-stage embryo transfer: a report of two cases and a review.

BACKGROUND: We describe two cases of dichorionic triplet pregnancy after a frozen-thawed poor-stage embryo transfer. A 39-year-old and a 41-year-old woman underwent ART treatment. The first patient underwent intracytoplasmic sperm injection (ICSI) at 34 years of age, and two frozen-thawed poor-stage embryos were transferred at 39 years of age with assisted hatching, resulting in a trichorionic triamniotic triplet pregnancy. The second patient underwent ICSI, and two poor-grade blastocysts were transferred followed by assisted hatching, resulting in a dichorionic triamniotic triplet pregnancy. In the first case, the heartbeat of one monozygotic twin fetus had stopped on day 48 post-transfer (9 weeks 2 days), resulting in a dichorionic diamniotic twin pregnancy. A healthy boy and girl were delivered by elective caesarean section at 36 weeks, 5-days gestation. In the second case, the patient underwent selective reduction of the monochorionic twins, resulting in a single pregnancy that was vaginally delivered without any problems at 38 weeks 0-days gestation. SHORT CONCLUSIONS: Numerous factors may be associated with the development of a monochorionic pregnancy; however, controversies still remain. The present morphological grading for embryos is insufficient for inhibiting the development of a monochorionic pregnancy.

Tablet terminals: a useful tool to explain in vitro fertilization treatment.

BACKGROUND: Explanations that involve medical care treatment take time. This also applies to explanations of in vitro fertilization (IVF) in the field of infertility treatment. This is because the cause of infertility differs from couple to couple, and because the explanations must begin with the mechanism of pregnancy. Recently, explanations facilitated by tablet terminals have been used in the field of medicine. In the present study, the efficacy and problems of explanations facilitated by tablet terminals were evaluated and compared with the explanations of IVF facilitated by paper-based pamphlets. METHODS: A total of 249 couples were asked to read a paper-based pamphlet explaining IVF treatment, while 252 couples were asked to view an explanation on a tablet terminal. The patients then answered a seven-item questionnaire. The answers to the questionnaire were based on a three-point scale, and statistical analysis was performed with the Mann-Whitney U test. RESULTS: Patients responded that the explanation facilitated by the tablet terminal was significantly easier to understand for all seven questionnaire items (p <0.05). The answer 'I did not understand' was selected for the items related to 'The treatment fees' (4.8% of answers) and 'Things to take note of, such as consultation times' (6.7% of answers). CONCLUSION: While patients generally did not understand the mechanism of pregnancy, explanations of IVF treatment facilitated by a tablet terminal were found to be more effective than paper-based explanations, although there is room for improvement.

An abdominal ectopic pregnancy following a frozen-thawed ART cycle: a case report and review of the literature.

BACKGROUND: Ectopic pregnancy (EP) occurs in 1% of pregnancies and is reported to be more common in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies. An abdominal ectopic pregnancy (AEP) is a rare form of EP, and there are few reports of an AEP after IVF/ICSI. In this case report, a rare case of AEP after frozen-thawed cycle of ICSI is presented. CASE PRESENTATION: After a frozen-thawed cycle of ICSI, the beta-human chorionic gonadotropin (HCG) level at 4 weeks 0 days of gestation was 3.4 IU/L. Subsequent dysfunctional uterine bleeding was mistaken for menstruation; however, an AEP of 9 weeks with a fetal heart beat was observed by ultrasound. After the AEP was observed by ultrasound, it was extracted laparoscopically. CONCLUSION: A rare case of an AEP, which developed after frozen-thawed cycle of ICSI, presented with a very low serum HCG level. Even if the HCG titer is low, follow-up HCG levels and frequent medical examinations are necessary.

A comparison of the clinical outcomes of embryos derived from intracytoplasmic sperm injection after early fertilization check and conventional insemination using sibling oocytes.

PURPOSE: In order to identify the real contribution of early fertilization check (EFC) for reproductive outcome, we compared the developmental potential of embryos derived from intracytoplasmic sperm injection (ICSI) after EFS with those from conventional insemination in sibling oocytes. METHODS: Between April 2009 and April 2012, a total of 3249 oocytes in 386 patients were recruited following conventional insemination. Oocytes showing a second polar body (2ndPB) after an EFC were considered to be fertilized oocytes (IVF group), but, oocytes not showing a 2ndPB after EFC were placed into the ICSI group. The incidence of morphologically good embryos (MGE) on day 3, the blastocyst formation (BL), and the development of full blastocysts (full-BL) on day 5 were compared between the two groups. The clinical pregnancy rate was compared between the cycles with only conventional insemination or ICSI after EFC of the embryos being transferred. RESULTS: The fertilization rates in both the IVF and the ICSI groups were 48.1 and 73.9 %, respectively. The percentage of MGE in the ICSI group (40.8 %) was significantly lower than that in the IVF group (56.1 %, p < 0.01). The percentages of BL and full-BL in the ICSI group were significantly lower than those in the IVF group. The pregnancy rates were similar in both the groups. CONCLUSIONS: Checking fertilization earlier than the usual period contributed to an avoidance of lower fertilization. Moreover, the embryos derived from ICSI after EFC possessed a normal developmental potential.

Phase I/II multiinstitutional study of uterine artery embolization with gelatin sponge for symptomatic uterine leiomyomata: Japan Interventional Radiology in Oncology Study Group study.

PURPOSE: This multicenter prospective study was conducted to evaluate the safety and the efficacy of uterine artery embolization (UAE) with gelatin sponge for symptomatic leiomyomas. MATERIALS AND METHODS: Patients with symptomatic uterine leiomyomas were enrolled and treated with UAE. In phase I, nine patients were evaluated for safety. In phase II, 24 patients were accrued, and an intent-to-treat analysis was performed on all 33 patients. The primary endpoint was safety. Secondary endpoints included technical success, hospital stay, change in symptoms, leiomyoma volume on magnetic resonance (MR) imaging, and incidence of treatment failure. RESULTS: UAE procedures were performed for all 33 patients. Two patients were lost to follow-up at 3 and 12 months. The median follow-up period was 33.4 months. Minor adverse events (AEs) occurred in 10 patients (33%); major AEs of permanent amenorrhea and leiomyoma expulsion occurred in two (6%). The most common AE was transient amenorrhea. Technical success was achieved in all patients. The median hospital stay was 5 days. At 12 months after UAE, menorrhagia had improved in 90% of patients, pelvic pain in 78%, and bulk-related symptoms in 97%. The mean reduction in leiomyoma volume on MR imaging at 12 months was 61%. Treatment failure occurred in one patient, who underwent hysterectomy for recurrent menorrhagia at 21 months. CONCLUSIONS: UAE with gelatin sponge is safe, with efficacy comparable to other embolic agents based on published data. Gelatin sponge should be an option for UAE, but a prospective comparison versus other standard UAE embolic agents may be warranted.

Optimization of a novel nylon mesh container for human embryo ultrarapid vitrification.

OBJECTIVE: To evaluate the efficacy of a nylon mesh container in vitrification of human embryos and to determine the optimal osmotic pressure of the initial thawing solution. DESIGN: Retrospective analysis. SETTING: National Center for Child Health and Development, Tokyo, Japan. PATIENT(S): Infertile patients undergoing either in vitro fertilization or intracytoplasmic sperm injection in our hospital. INTERVENTION(S): Embryos, at the cleavage stage, were cryopreserved using the vitrification method in either a plastic straw or a nylon mesh container. The embryos were thawed using an initial osmotic pressure of either 0.5 M or 1.0 M sucrose with subsequent step-wise dilution. After thawing, the embryos were transferred to the uterus. MAIN OUTCOME MEASURE(S): Survival rate of blastomeres, embryo survival rate, implantation, and pregnancy rates, cancellation rate because of embryo damage. RESULT(S): Use of nylon mesh and the 1.0 M sucrose thawing solution significantly improved blastomere survival rate (98.0 +/- 1.0%, mean +/- SEM), pregnancy rate (41.0%) and implantation rate (32.3%). CONCLUSION(S): Vitrification using a nylon mesh container and subsequent thawing in a 1.0 M sucrose solution is an easy and inexpensive method that improves the reliability of embryo cryopreservation of embryos without adverse effects on clinical outcomes.

Laparoscopically-assisted transabdominal oocyte retrieval in an infertility patient with ovarian malposition.

Infertility patients with malpositioned ovaries have considerable difficulty conceiving naturally because of extended fallopian tubes and ovarian malposition; such patients turn for help to assisted reproductive technology (ART) treatment. For most of these patients, ovarian malposition prevents transvaginal oocyte retrieval, so the transabdominal approach for oocyte retrieval is required. One of our infertility patients presented with ovarian malposition, and laparoscopy-assisted transabdominal oocyte retrieval was performed. We performed a Gonadotropin-releasing hormone agonist (GnRH-a) long protocol with human menopausal gonadotropin (hMG) ovarian stimulation, and used a standard transvaginal probe through the anterior abdominal wall for ovarian imaging and monitoring of the growing follicles. The patient underwent laparoscopically-assisted transabdominal oocyte retrieval-9 oocytes were recovered, and 5 were fertilized, and 2 embryos were transferred to the patient's uterus. The patient became pregnant and a gestational sac was detectable by transvaginal ultrasonography, but she spontaneously miscarried. The patient then received several laparoscopically-assisted transabdominal oocyte retrievals and finally became pregnant following a thawed embryo transfer during a hormone replacement cycle, and now her pregnancy is going well.

Laparoscopic proximal tubal division can preserve ovarian reserve for infertility patients with hydrosalpinges.

AIM: To investigate whether laparoscopic proximal tubal division for the treatment of hydrosalpinges could preserve ovarian function. METHODS: From June 2002 to October 2006, before assisted reproductive treatment (ART), a total of 17 infertile patients with bilateral hydrosalpinges were studied--11 patients underwent laparoscopic proximal tubal division (PTD group), and six underwent laparoscopic salpingectomy (salpingectomy group). In both groups, the basal follicle-stimulating hormone (FSH) values before and after surgery, the operation time and outcome of ART treatment were retrospectively evaluated. RESULTS: The mean FSH value before laparoscopic PTD was similar to that after surgery. The FSH value before laparoscopic salpingectomy significantly increased after surgery (6.8 +/- 1.1 vs 14.1 +/- 9.3). The operation time in the PTD group was significantly shorter than in the salpingectomy group. The outcomes of ART were similar in both groups. The pregnancy rate per patient in the PTD and salpingectomy groups were 45.5% and 50%, respectively. CONCLUSIONS: Laparoscopic proximal tubal division preserved ovarian function and was an optimal operation method for infertility patients with hydrosalpinges. The basal FSH values after laparoscopic proximal tubal division were comparable to those before surgery.

The ratio of late-follicular to mid-follicular phase LH concentrations efficiently predicts ART outcomes in women undergoing ART treatment with GnRH-agonist long protocol and stimulation with recombinant FSH.

PURPOSE: To establish an index to predict ART outcomes and to identify infertile patients who need LH supplementation during ovarian stimulation. METHODS: Serum LH concentrations were measured during the mid- and late-follicular phase in 86 normogonadotropic infertile patients who underwent ART treatment using GnRH-agonist long protocol with recombinant-FSH. The relationships between serum LH concentrations at both time points and ART outcomes were retrospectively analyzed, and the relationships between the ratio of late-follicular to mid-follicular LH concentrations and ART outcomes were also evaluated. RESULTS: There were no significant correlations between the mid- or late-follicular LH concentrations and ART outcomes. The ratio of late-follicular to mid-follicular LH concentrations <1.0 was considered the relatively LH decreased group (RD group) and ratio >or= 1.0 was considered the relatively LH increased group (RI group). The number of usable embryos in RD group was similar to that in RI group, but the pregnancy and implantation rates in the RD group (9.7% and 5.8%) were significantly lower than those in the RI group (31.1% and 17.2%; p < 0.05). CONCLUSIONS: Relatively decreased LH concentrations during ovarian stimulation using GnRH-agonist long protocol with rec-FSH had a negative effect on ART outcomes. Therefore, the ratio of mid- to late-follicular phase LH concentrations is suggested to be an efficient index to identify patients who might benefit from LH supplementation.

[Aging and anti-aging of oocytes].

The functions of organs decrease as the age increases. The fecundity of women also decreases due to mainly the decreasing quality of oocytes. The recent change of life style makes the age of infertility patients elder and infertility treatments more difficult. The therapeutic strategy for the elder infertility patients is still chaotic. The precise evaluation for the ageing in the female genital organs should be developed and the treatment for the failure of fecundity due to aging must be overcome.

The frequency of ovulation from the affected ovary decreases following laparoscopic cystectomy in infertile women with unilateral endometrioma during a natural cycle.

PURPOSE: To evaluate the cystectomy-induced damage on the follicular growth and ovulation of an affected ovary during natural cycles. METHODS: Twenty-eight infertile patients with unilateral ovarian endometriomas who underwent laparoscopic cystectomy were retrospectively evaluated. The ovulation rate of an affected ovary during natural cycles was compared before and after cystectomy in each patient, and it was also determined if ovulation from the affected ovaries resulted in pregnancy. RESULTS: After surgery, the ovulation rate was significantly lower than that before cystectomy (16.9 +/- 4.5% vs. 34.4 +/- 6.6%, P = 0.013). After surgery, 14 pregnancies were achieved without IVF treatment, and only 2 of them (14.3%) were achieved from an operated-side ovary. However, the pregnancy rate per ovulatory cycle of the operated-side ovary was not different from that of the intact ovary (8.8% vs. 5.8%, P = 0.750). CONCLUSIONS: Laparoscopic cystectomy is an invasive treatment in that it reduces the frequency of ovulation; however the pregnancy rate per ovulation did not deteriorate.

Elevated basal FSH levels, if it is under 15 IU/L, will not reflect poor ART outcomes.

PURPOSE: For this study, the impact of basal FSH levels on ART outcomes was assessed. METHODS: From June 2003 to May 2006, 191 ART cycles were performed in our hospital. All cases were treated with GnRH-a long protocol. The patients were classified according to their basal FSH level as follows: group A: FSH <10 IU/l, group B: 10

Insulin resistance in oligomenorrheic infertile women with non-polycystic ovary syndrome.

OBJECTIVE: To determine whether infertile oligomenorrheic women are insulin resistant, using an oral glucose tolerance test (OGTT). DESIGN: Retrospective study. SETTING: National Center for Child Health and Development. PATIENT(S): One hundred twenty-seven infertile women with oligomenorrhea (oligomenorrheal group) and 177 infertile eumenorrheic women (normal menstrual group) were recruited. INTERVENTION(S): All women underwent an OGTT (75 g glucose). MAIN OUTCOME MEASURE(S): A homeostasis model assessment of insulin resistance (HOMA-IR), area under the curve (AUC) of insulin after the glucose load, and plasma insulin level at 120 minutes after glucose loading (IRI 120) were used as an index of insulin resistance. RESULT(S): The prevalence of insulin resistance (HOMA-IR >or=1.73) among oligomenorrheic women was 23.8%, which was significantly higher than that of eumenorrheic women, at 14.1%. The glucose AUCs (mean +/- SE) in the oligomenorrheal group (13,609 +/- 259 mg/min/dL) were similar to those for the normal menstrual groups (13,054 +/- 196 mg/min/dL), but the insulin AUCs of the oligomenorrheal group (5333 +/- 376 mU x min/L) were significantly higher than those of the normal menstrual groups (4517 +/- 266 mU x min/L). CONCLUSION(S): The prevalence of insulin resistance assessed using an OGTT was significantly higher among infertile oligomenorrheic women with non-polycystic ovary syndrome than it was among women with normal menstrual cycles.

Glutathione S-transferase theta 1 expressed in granulosa cells as a biomarker for oocyte quality in age-related infertility.

OBJECTIVE: The goal of this study was to identify a reliable biomarker for age-related infertility. DESIGN: Laboratory study. SETTING: ART laboratory. PATIENT(S): Patients undergoing intracytoplasmic sperm injection or IVF cycles. INTERVENTION(S): Expression of Glutathione S-transferase (GST) mRNA and protein in mural and cumulus granulosa cells obtained from infertile patients were examined by reverse transcriptase-polymerase chain reaction and immunofluorescence. MAIN OUTCOME MEASURE(S): Correlation between the expression of GST theta 1 (GSTT1) in granulosa cells and oocyte quality was a main outcome measure. RESULT(S): Expression of GSTT1 in granulosa cells from male factor patients was positively correlated with age and negatively with cumulus-oocyte complex maturity. When samples with high and low GSTT1 in granulosa cells were extracted from the other infertility factors, cumulus-oocyte complex maturity in the high GSTT1 group was significantly lower than that in the low GSTT1 group (high: 27.2% vs. low: 51.3%). The developmental capacity of oocytes in the high GSTT1 group was likely to be lower (high: 26.4% vs. low: 43.9%). Up-regulation of GSTT1 during aging may be promoted by FSH and H(2)O(2), determined by an in vitro model. CONCLUSION(S): GSTT1 is a good indicator for age-related infertility.