OBJECTIVE: Is the mode of conception (natural, subfertility and non-IVF, and IVF) associated with the risk of Type 1 diabetes mellitus among offspring?
CONCLUSIONS: The risk of Type 1 diabetes in offspring does not differ among natural, subfertility and non-IVF, and IVF conceptions.
BACKGROUND: Evidence has shown that children born through IVF have an increased risk of impaired metabolic function.
METHODS: A population-based, nested case-control study was carried out, including 769 children with and 3110 children without Type 1 diabetes mellitus within the prospective cohort of 2 228 073 eligible parent-child triads between 1 January 2004 and 31 December 2017.
METHODS: Using registry data from Taiwan, the mode of conception was divided into three categories: natural conception, subfertility, and non-IVF (indicating infertility diagnosis but no IVF-facilitated conception), and IVF conception. The diagnosis of Type 1 diabetes mellitus was determined according to the International Classification of Diseases, 9th or 10th Revision, Clinical Modification. Each case was matched to four controls randomly selected after matching for child age and sex, residential township, and calendar date of Type 1 diabetes mellitus occurrence.
RESULTS: Based on 14.3 million person-years of follow-up (median, 10 years), the incidence rates of Type 1 diabetes were 5.33, 5.61, and 4.74 per 100 000 person-years for natural, subfertility and non-IVF, and IVF conceptions, respectively. Compared with natural conception, no significant differences in the risk of Type 1 diabetes were observed for subfertility and non-IVF conception (adjusted odds ratio, 1.04 [95% CI, 0.85-1.27]) and IVF conception (adjusted odds ratio, 1.00 [95% CI, 0.50-2.03]). In addition, there were no significant differences in the risk of Type 1 diabetes according to infertility source (male/female/both) and embryo type (fresh/frozen).
CONCLUSIONS: Although the population-level data from Taiwanese registries was used, a limited number of exposed cases was included. We showed risk of Type 1 diabetes was not associated with infertility source or embryo type; however, caution with interpretation is required owing to the limited number of exposed events after the stratification. The exclusion criterion regarding parents\' history of diabetes mellitus was only applicable after 1997, and this might have caused residual confounding.
CONCLUSIONS: It has been reported that children born to parents who conceived through IVF had worse metabolic profiles than those who conceived naturally. Considering the findings of the present and previous studies, poor metabolic profiles may not be sufficient to develop Type 1 diabetes mellitus during childhood.
BACKGROUND: This study was supported by grants from Shin Kong Wu Ho-Su Memorial Hospital (No. 109GB006-1). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. The authors have no competing interests to disclose.
BACKGROUND: N/A.

BACKGROUND: Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers currently lack consensus regarding the methods for preventing and managing embryo culture infection. In our recent case, a successful pregnancy was achieved with intracytoplasmic sperm injection after failed conventional in vitro fertilization owing to bacterial contamination.
METHODS: We present a case report of two consecutive in vitro fertilization-intracytoplasmic sperm injection cycles with photo and video documentation of the bacterial growth. A 36-year-old Hungarian woman and her 37-year-old Hungarian partner came to our department. They had two normal births followed by 2 years of infertility. The major causes of infertility were a closed fallopian tube and asthenozoospermia. Bacterial infection of the embryo culture medium was observed during in vitro fertilization and all oocytes degenerated. The source was found to be the semen. To prevent contamination, intracytoplasmic sperm injection was used for fertilization in the subsequent cycle. Intracytoplasmic bacterial proliferation was observed in one of the three fertilized eggs, but two good-quality embryos were successfully obtained. The transfer of one embryo resulted in a successful pregnancy and a healthy newborn was delivered.
CONCLUSIONS: Intracytoplasmic sperm injection may be offered to couples who fail conventional in vitro fertilization treatment owing to bacteriospermia, as it seems to prevent infection of the embryo culture. Even if bacterial contamination appears, our case encourages us to continue treatment. Nevertheless, the development of new management guidelines for the prevention and management of bacterial contamination is essential.

OBJECTIVE: Failure to collect oocytes at the time of oocyte pick-up is an unfavorable outcome of in vitro fertilization (IVF) cycles. In these cases, prompt intrauterine insemination (IUI) could be an option (rescue IUI), but this possibility has been poorly studied.
METHODS: Rescue IUI is routinely offered in our unit in women failing to retrieve oocytes, provided that they have at least one patent tube, normal male semen analysis, and the total number of developed follicles is ≤ 3. We therefore reviewed all oocyte retrievals performed from 2006 to 2022 in our unit to identify these cases. As a comparator, we referred to preplanned IUI performed during the same study period. The 95% confidence interval (95% CI) of proportions was calculated using a binomial distribution model.
RESULTS: Rescue IUI was performed in 96 out of 3531 oocyte retrievals (2.7%; 95% CI 2.2-3.3%). Six live births were obtained, corresponding to 6.2% (95% CI 2.3-13.1). All pregnancies were singletons.
CONCLUSIONS: Rescue IUI in women failing to retrieve oocytes is a possible option that may be considered in selected cases. The efficacy is low, but the procedure is simple, and without significant risks. Generalizability to a conventional IVF protocol setting is however limited.

We report a successful case for the clinical efficacy of the endometrial receptivity array (ERA) test for a 32-year-old female patient with refractory infertility. After our careful treatment, the patient gave birth to a male baby (3390 g) in November 2021. To our knowledge, though the clinical efficacy of the ERA test is controversial until March 2024, we think that the age of the patients, the number of IVF cycles, and the racial differences may have an impact on the clinical efficacy of the ERA test.

OBJECTIVE: To evaluate whether a second biopsy, following a first diagnostic failure on blastocysts tested for preimplantation genetic testing for monogenic diseases (PGT-M), allows to obtain genetic diagnosis and to what extent this procedure can influence clinical pregnancy and live birth rates compared to the PGT-M process with a successful genetic diagnosis from the first biopsy.
METHODS: Embryos from women who underwent PGT-M in an infertility centre and who had been transferred after two biopsies for genetic analysis (n = 27) were matched in a 1:1 ratio accordingly to women\'s age (± 1 year) and fertility status (fertile vs infertile), as well as with the study period, with embryos who were transferred after receiving a conclusive PGT result straight after the first biopsy (n = 27). The main evaluated outcome was clinical pregnancy rate following embryo transfers in which healthy embryos were transferred after only one biopsy and those in which an embryo was transferred after being re-biopsied. Live birth rate was the secondary outcome.
RESULTS: Clinical pregnancy rate was 52% (95% CI: 34-69) following the transfer of a single-biopsy blastocyst and 30% (95% CI: 16-48) following the transfer of a re-biopsied blastocyst. The likelihood to have a healthy baby was 33% (95% CI: 19-52) following the transfer of a blastocyst biopsied once and 22% (95% CI: 11-41) following the transfer of a re-biopsied blastocyst.
CONCLUSIONS: The re-biopsy intervention seems to considerably reduce the pregnancy potential of a blastocyst. However, a greater sample size is necessary to clarify this issue definitively.

UNASSIGNED: In in vitro fertilization (IVF), laser offers several advantages. In this study, we employed laser to eliminate the zona pellucida of a contaminated embryo. This approach helps to rescue embryo with bacterial contamination, and improve embryo-endometrium interaction.
UNASSIGNED: To present a case report on the removal of a contaminated zona pellucida from an embryo of patient with a history of recurrent implantation failure (RIF), which was followed by a successful live birth. We present the case of a 34-year-old patient with a history of 3 years of infertility who underwent in vitro fertilization. During the culture process, the embryos became contaminated, leading to three failed implantations. Despite the aneuploidy of the embryo and the implementation of a washing technique, the contamination persisted. In the final attempt, the contaminated zona pellucida was successfully removed using laser, followed by embryo transfer, resulting in a live birth. We provided detailed clinical information, including patient demographics, infertility history, ovarian response, evidence of bacterial contamination, embryo development, treatment protocols, and outcomes. Laser excision of the zona pellucida is a safe and effective method for addressing bacterial infection in embryos.

Idiopathic ventricular fibrillation (IVF) is a diagnosis of exclusion in sudden cardiac arrest (SCA) survivors. Although there are clear guidelines on the clinical work-up of SCA survivors, less than one in five patients receives a complete work-up. This increases the chances of erroneously labelling these patients as having IVF, while 10-20% of them have an inherited cardiac condition (ICC). Diagnoses of ICC increase over time due to (additional) deep phenotyping or as a result of spontaneous expression of ICC over time. As SCA survivors can also harbor (likely) pathogenic variants in cardiomyopathy-associated genes in the absence of a phenotype, or can have another ICC without a clear cardiac phenotype, the question arises as to whether genetic testing in this group should be routinely performed. Family history (mainly in the case of sudden death) can increase suspicion of an ICC in an SCA victim, but does not add great value when adults underwent a complete cardiological work-up. The diagnosis of ICC has treatment consequences not only for the patient but also for their family. Genetic diagnostic yield does not appear to increase with larger gene panels, but variants of unknown significance (VUS) do. Although VUS can be confusing, careful and critical segregation analysis in the family can be performed when discussed in a multidisciplinary team at a center of expertise with at least a cardiologist as well as a clinical and laboratory geneticist, thereby degrading or promoting VUS. When to introduce genetic testing in SCA survivors remains a matter of debate, but the combination of quick, deep phenotyping with additional genetic testing for the unidentifiable phenotypes, especially in the young, seems preferable.
UNASSIGNED: Idiopathisches Kammerflimmern („idiopathic ventricular fibrillation“ [IVF]) ist eine Ausschlussdiagnose bei Überlebenden eines plötzlichen Herzstillstands („sudden cardiac arrest“ [SCA]). Obwohl es eindeutige Leitlinien für die klinische Abklärung von SCA-Überlebenden gibt, erhält weniger als einer von fünf betroffenen Patienten eine vollständige Diagnostik. Dadurch erhöht sich das Risiko einer falschen Diagnose von IVF bei diesen Patienten, von denen 10–20% eine erbliche Herzerkrankung („inherited cardiac condition“ [ICC]) haben. ICC-Diagnosen nehmen mit der Zeit zu, bedingt durch (zusätzliche) umfassende Phänotypisierung oder als Ergebnis einer spontanen ICC-Manifestation im Verlauf. Da SCA-Überlebende auch Träger (wahrscheinlich) pathogener Varianten kardiomyopathieassoziierter Gene bei Fehlen eines Phänotyps sein können oder eine andere ICC ohne eindeutigen kardialen Phänotyp aufweisen können, stellt sich die Frage, ob in dieser Patientengruppe eine genetische Diagnostik routinemäßig durchgeführt werden sollte. Die Familienanamnese (hauptsächlich bei plötzlichem Todesfall) kann den Verdacht auf eine ICC bei Patienten mit SCA erhärten, hat aber keinen hohen zusätzlichen Wert, wenn Erwachsene einer vollständigen kardiologischen Abklärung unterzogen worden sind. Die Diagnose einer ICC hat nicht nur für den Patienten, sondern auch für dessen Familie therapeutische Konsequenzen. Die gendiagnostische Ausbeute scheint sich mit größeren Genpanels nicht zu erhöhen, anders verhält es sich in Bezug auf Varianten mit ungeklärter Relevanz („variants of unknown significance“ [VUS]). Auch wenn VUS für Verwirrung sorgen können, kann eine sorgfältige und kritische Segregationsanalyse in der Familie durchgeführt werden, wenn sie in einem multidisziplinären Team an einem spezialisierten Zentrum mit zumindest einem Kardiologen, einem klinischen Genetiker und einem im Laborbereich tätigen Genetiker („laboratory geneticist“) diskutiert wird, woraufhin die VUS hinsichtlich ihrer Bedeutung verworfen oder gestärkt wird. Wann die genetische Diagnostik bei SCA-Überlebenden einbezogen werden soll, ist eine Frage, über die weiter debattiert wird. Die Kombination einer schnellen, umfassenden Phänotypisierung mit zusätzlichen Gentests für die unidentifizierbaren Phänotypen scheint aber zu bevorzugen zu sein, insbesondere bei jungen Patienten.

Multiple pregnancies are associated with significant maternal, fetal, and neonatal risks, including prematurity, low birth weight, pre-eclampsia, anemia, postpartum hemorrhage, intrauterine growth restriction, neonatal morbidity, and increased neonatal and infant mortality rates. Assisted reproductive technology (ART) treatments should prioritize efforts to reduce such events, resisting patient demand for the transfer of multiple embryos at each transfer to increase success rates. Extended culture, embryo selection, and single blastocyst transfer can mitigate the risk of high-order multiple pregnancies. Intriguingly, elective single-embryo transfer (eSET) greatly reduces, but does not completely eliminate, the likelihood of multiple gestations. The occurrence of monozygotic twinning (MZT) gives rise to identical twins. It is more prevalent in women undergoing in vitro fertilization (IVF) compared with natural conception. In fact, the reported risks of monozygotic twinning in IVF and natural conception are 1.7 and 0.4%, respectively. The factors suspected to increase the risk of MZT in IVF are multiple embryo transfer, micromanipulation, and extended in vitro culture. Determining chorionicity and amnionicity is crucial in the assessment of multiple pregnancies during the first-trimester ultrasound examination. Dichorionic twins result from embryo splitting within 3 days after fertilization, while monochorionic twins occur when the splitting takes place between 4 and 8 days after fertilization. These timings are suggested by observations carried out in natural pregnancies. In ART, there is evidence of dichorionic twins derived from single embryo transfer (SET). Here, we report a case of dichorionic diamniotic triplets after a single blastocyst transfer occurred in our center. To our knowledge, this is the first case documented so far.

Superfetation is a very rare occurrence. In the context of assisted reproduction, it has been reported only as an intrauterine pregnancy after ovarian stimulation and/or embryo transfer in the presence of an undiagnosed ectopic pregnancy. Here we report a case of a 27-year-old anovulatory patient, gravida 1 para 1, who underwent two frozen-thawed single-blastocyst transfers in separate cycles. The patient reported that 12 days after the first transfer, she had menstrual bleeding and stopped her estradiol and progesterone supplementation without undergoing a blood human chorionic gonadotropin (βhCG) test. At her request, a second cycle was immediately initiated, with endometrial thickness measuring 4 mm. Eleven days after the second transfer, the βhCG value was inappropriately high. A right tubal pregnancy corresponding to 8 gestational weeks was diagnosed. Laparoscopy revealed a prominent right tubal pregnancy in addition to a significantly smaller left tubal pregnancy. The discordant tubal pregnancies were confirmed histologically. To our knowledge, superfetation involving a second ectopic pregnancy coexistent with a first, contralateral ectopic pregnancy consequent to consecutive in vitro fertilization procedures has not previously been described in the medical literature. This case emphasizes the importance of routine βhCG testing after every IVF cycle, even if apparently unsuccessful.

A 29-year-old female who received assisted reproductive therapy (IVF) in our infertility clinic, at gestational age of 7w + 2d following embryo transfer, presented with a favorable rise of β-hCG level with no detectable gestational sac in the uterine cavity in the vaginal ultrasonogram. First dose of MTX (78) with simultaneous β-hCG titration of 110,000 pg/mL was administered. The patient underwent a second TVS in which a mass in favor of molar ectopic pregnancy was reported. With the suspicion of a molar EP the patient underwent explorative laparotomy. A 3x4 cm mass which was found adjacent to the right ovary was resected. Final pathology report was compatible with partial molar pregnancy. In the follow up period after surgical resection the patient recovered completely without any recurrence.