Chao-Chin Hsu

Objectives: This study aimed to investigate the correlation of ovarian sensitivity index (OSI) and clinical parameters in IVF treatments.Methods: IVF data files between January 2011 and December 2020 in a single unit were included. The primary outcome measure was the correlation between the OSI and clinical pregnancy and live birth rates. A generalized linear model was employed to assess group differences while controlling for age. Correlations between the OSI and clinical parameters were analyzed using Pearson’s correlation test.Results: In total, 1,627 patient data were reviewed, comprising 1,160 patients who received GnRH antagonists and 467 who received GnRH agonists. There was no difference in the incidence of premature ovulation and LH surge in women receiving either GnRH antagonists or agonists. A higher number of mature oocytes and good embryos were obtained in the GnRH agonist cycles. No differences were observed in pregnancy and live birth rates between both groups. Regarding the correlation of the OSI with clinical parameters, serum anti-Müllerian hormone, cycle day 2 follicle-stimulating hormone, LH, and estradiol concentrations, numbers of larger follicles, fertilization rate, and the incidence of premature LH surge were positively correlated with the OSI. Whereas the body mass index, mature oocytes obtained, embryo transfer number, and dose of GnRH antagonists were negatively correlated with the OSI. In the GnRH antagonists group, an OSI of 225.75 significantly distinguished pregnancy from non-pregnancy (p < 0.001), with an AUC of 0.615, and an OSI of 208.62 significantly distinguished live births from non-live births (p < 0.001), with an AUC of 0.637. As for the GnRH agonist group, an OSI of 228 significantly distinguished live births from non-live births, (p =0.020) with an AUC of 0.569.Conclusion: We demonstrated the capability of employing OSI to distinguish the clinical pregnancy and live birth outcomes in IVF cycles.

Background: Fallopian tube serous adenofibromas are uncommon tumors of the female genital tract, only dozens of cases have ever been reported. Earlier study indicated that they might be derived from embryonic remnants of the Müllerian duct. Clinical presentation of these tumors is usually asymptomatic. Small cysts of 0.5–3 cm in diameter are mostly incidentally found at the fimbriae end, with coarse papillary excrescences lined by epithelial cells and connective tissue stroma without nuclear pleomorphism or mitosis. Case presentation: A 23-year-old woman with normal secondary sexual characters and 46, XX karyotype, presented to the gynecology clinic complaining of irregular menstrual cycles. Laboratory studies reported unique discrepancy of hormone levels; anti-Müllerian hormone (AMH): 6.05 ng/mL (The normal range of AMH is 1.70–5.63 ng/mL in women aged under 35 years old), follicle stimulating hormone (FSH): 31.9 mIU/mL (reference range: 3.85–8.78, follicular phase; 4.54–22.51, ovulatory phase; 1.79–5.12, luteal phase; 16.74-113.59, menopause), and luteinizing hormone (LH): 52.0 mIU/mL (reference range: 2.12–10.89, follicular phase; 19.18-103.03, ovulatory phase; 1.20-12.86, luteal phase; 10.87–58.64, menopause), mimicking gonadotropin-resistant ovary syndrome. The ultrasound reported a right adnexal cyst of 10.4 × 7.87 × 6.7 cm. Laparoscopic evaluation was performed; pathology revealed serous adenofibroma of the fallopian tube with ovarian stroma contents. Heterotopic extraovarian sex cord-stromal proliferations was most probable. The patient’s hormone levels returned to the reproductive status two weeks after surgery; FSH: 7.9 mIU/mL, LH: 3.59 mIU/mL,and AMH: 4.32 ng/mL. The patient’s menstrual cycles have resumed to normal for over two years after removal of the fallopian tube cyst. Conclusions: This case of fallopian tube serous adenofibromas presented a discrepancy of serum AMH and FSH mimicking gonadotropin-resistant ovary syndrome. The clinical picture derived from heterotopic extraovarian sex cord-stromal proliferation indicated a disordered hypothalamus-pituitary-ovary axis.

It is a challenge to obtain sufficient eggs during in vitro fertilization (IVF) in women with impending ovarian failure (IOF)/diminished ovarian reserve (DOR). Although studies have suggested that more than one wave of follicle growth exists, the efficacy of controlled ovulation stimulation (COS) in both follicular and luteal phases of the same ovarian cycle (DuoStim) is not established in women with IOF/DOR. We investigated the efficacy of DuoStim using the intraovarian injection of recombinant human follicle-stimulating hormone (rhFSH) during oocyte retrieval in women with DOR. For luteal-phase stimulation, intraovarian (Group A, N = 28) or superficial subcutaneous (Group B, N = 18) injection of 300 IU rhFSH immediately after oocyte retrieval was administered as the first dose, and intermittent superficial subcutaneous addition of gonadotropins was employed accordingly for further COS in both groups. In Group A, significantly lower Gn doses, a shorter duration of COS, a greater number of antral follicle counts, and an increased number of retrieved mature and total oocytes were noted. Compared with the clinical outcomes of luteal-phase COS, the average daily doses of rhFSH used in Group A were significantly lower. In summary, the novel approach using intraovarian rhFSH injection provides an efficient treatment regimen in women with IOF/DOR.

It is a challenge to obtain enough oocytes during in vitro fertilization (IVF) in women who have a poor ovarian response (POR) in achieving conception. We have adopted the characteristics of the first uterine pass effect, which we pioneered in employing the vaginal administration of gonadotropins in women receiving IVF treatments. In our previous study employing vaginal administration, faster absorption and slower elimination of gonadotropins were demonstrated, and, female subjects presented proper ovarian follicle growth and pregnancy rates. In this study, during 2016–2020, 300 to 675 IU of gonadotropins were administered vaginally every three days in 266 POR women for their controlled ovarian hyperstimulation (COH). The injections were performed with needles angled at 15–30° towards the middle-upper portions of the bilateral vaginal wall, with an injection depth of 1–2 mm. For the COH results, these women, on average, received 3.0 ± 0.9 vaginal injections and a total dose of 1318.4 ± 634.4 IU gonadotropins, resulting in 2.2 ± 1.9 mature oocytes and 1.0 ± 1.2 good embryos. Among these embryos, 0.9 ± 1.0 were transferred to reach a clinical pregnancy rate of 18.1% and a live birth rate of 16.7%. In conclusion, the intermittent vaginal administration of gonadotropins proved to be effective in POR women for their IVF treatments.

Background: Delayed childbearing has been noted in a high percentage of women with a previous Caesarean section (CS). Many women with CS scar defects (CSDs) present with clinical symptoms of irregular vaginal bleeding. The present study aimed to investigate bacterial colonies at CSDs in women suffering from secondary infertility. Methods: This observational study included 363 women with secondary infertility who visited the Assisted Reproduction Unit between 2008 and 2013. Among them, 172 women with a previous CS and 191 women with no previous CS were approached. The women with a previous CS had their CS operations in the past 1 to 14 years, with a mean of 3.5 years. The presence of CSDs was detected by vaginal ultrasonography. Bacteriology cultures of specimens taken from the uterine niches in those with CSDs were collected during Day 7 to Day 10 of the follicular phase. Specimens were obtained from the endocervical canal for bacterial culture in those without CSDs. The main outcome measure was the detection of the growth of bacterial colonies. Results: CSDs were found in 60.4% (96 of 159) of women with a previous CS. In women with a previous CS, bacterial colonies were identified in 89.6% (86 of 96) and 69.8% (44 of 63) of women with and without CSDs, respectively. In women with no previous CS, 49.7% (88 out of 177) of bacterial cultures of endocervical samples showed bacterial colony growth. Gram-positive cocci (P = 0.0017, odds ratio (OR) = 1.576, 95% confidence intervals (CI) -22.5 to − 5.4) and Gram-negative rods (P = 0.0016, OR = 1.74, CI − 20.8 to − 5.0) were the most commonly isolated bacteria and contributed to approximately 90% of all microorganisms found in those with a previous CS. In women with a previous CS, more Gram-negative rods were isolated (P = 0.01, OR = 1.765, CI − 27.2 to − 3.8), especially Pseudomonas species (P = 0.02, OR = 1.97, CI − 16.7 to − 1.0), in those with visible CSDs than in those without CSDs. Conclusions: Bacterial colonization at CSDs was found in a high percentage of women with secondary infertility.

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T_1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.

Context: Gonadotropins can be administered every 5 days under intradermal injection in in vitro fertilization (IVF) treatment.Objective: To explore the effectiveness of intradermal injection of recombinant human FSH (rhFSH) for women undergoing IVF.Methods: Women who received their first IVF treatment enrolled in this prospective intervention in 2018. All women received a bolus of 900 IU rhFSH intradermally at day 2 of the treatment cycle followed by additional dosage of rhFSH at day 7 and/or day 10. The main outcome measures included the total dose of rhFSH and number of injections required, sequential serum FSH level detected, and number of mature oocytes retrieved.Results: Seventy women completed the study. On average, 2.31 ± 0.73 injections and 1662 ± 397 IU of rhFSH were administered. While the baseline FSH level was 5.6 ± 2.2 IU/L, the serum concentrations of FSH after rhFSH administration were 35.3 ± 7.0 on the first day (24 hours) and 10.7 ± 3.7 IU/L on the fifth day (120 hours). A total of 10.5 ± 6.6 mature oocytes were retrieved, resulting in 7.3 ± 5.1 pronuclear embryos; 1.8 ± 0.6 embryos were transferred to the uterus. Our findings resulted in 72% fertilization, 91% cleavage, 31% implantation, and 36% live birth rates. Although fewer larger follicles were found, noninferiority results were noted in the mature oocytes retrieved, good embryos available, and clinical pregnancy rate compared with those received conventional daily subcutaneous rhFSH administration.Conclusion: Intradermal administration of rhFSH, with a smaller dose of rhFSH and fewer injections, may achieve the goal of a cost-effective and more patient-friendly regimen.

Objective: This study was designed to investigate if whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin, in proximity to most ovarian follicles, is effective in restoring ovarian functions in women during early menopause. Methods: Platelet-rich plasma, prepared from 40 mL of autologous peripheral blood using the buffy coat method, was injected into extended subcortical area of bilateral ovaries along with recombinant follicle-stimulating hormone (rFSH) (Gonal-F 300IU) under laparoscopic guidance. The posttreatment ovarian folliculogenesis and serum levels of FSH, luteinizing hormone (LH), and estradiol were followed up for 6 months at weekly to monthly intervals. IVF was carried out in women resuming ovulatory functions. Results: Twelve early menopausal women with mean age of 44.42 ± 2.84 were enrolled. After treatment, 11 women resumed their menstrual period in 37.1 ± 23.5 days. Their average serum FSH was 70.47 ± 20.92 and 26.22 ± 17.55 IU/L, luteinizing hormone was 34.81 ± 11.86 and 14.3 ± 12.8 IU/L, before and after treatment, respectively. The mid-cycle E2 was 251.1 ± 143.8 pg/mL. Ten oocyte retrievals were carried out among six participants, four of them received controlled ovarian stimulation and another two using natural ovulation cycles. Thirteen mature eggs were retrieved which were then ICSI fertilized to obtain 10 normally fertilized 2PN oocytes. Two participants had cleavage stage embryos transferred of which one achieved clinical pregnancy. Conclusions: Whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin was shown to restore ovarian functions, at least temporarily, and could increase the probability of pregnancy using autologous oocytes in women with early menopause.

BackgroundWomen undergoing IVF treatments have to receive daily injections of rFSH for multiple follicles growth based on the short half-life of rFSH administered subcutaneously. This study was designed to assess if longer intervals of injection, based on rFSH half-life of 102 hours under superficial subcutaneous administration, effective for women receiving IVF.MethodsOne hundred women, aged 25–45, requesting IVF treatments from January to December 2018 were recruited in this observatory study. All women received long protocol employing GnRH-agonist since day 18 of the previous cycle. An initial bolus of 900 IU rFSH was injected into superficial subcutaneous skin at day 2 of the treatment cycle followed by longer intervals with added doses at day 7 and/or day 10. The main outcomes included the dose of gonadotropin and numbers of injection, serum FSH level, and mature oocytes retrieved.ResultsA total of 70 women completed the treatments, in which 10, 30, and 30 women received one, two and three injections of rFSH, respectively. On average, 2.31 ± 0.73 numbers of Gn injection and 1662 ± 397 IU of rFSH were administered. In comparison with baseline FSH level of 5.6 ± 2.2 IU/L, the serum concentrations of FSH were 35.3 ± 7.0 to 10.7 ± 3.7 IU/L at 1 to 5 days after an initial 900 IU rFSH administration. There were 10.5 ± 6.6 mature oocytes retrieved which resulted in 7.3 ± 5.1 two pronuclei embryos, and 1.8 ± 0.6 embryos were transferred back to the uterus and the remaining embryos were cryopreserved. In total, 72%, 91%, and 31% were noted for fertilization, cleavage, and implantation rates, respectively. The cumulative live birth rate was 36%.ConclusionsBased on the serum FSH levels detected, rFSH only needs to be administered every five days instead of daily injection. This administration mode with less injections and much less expenses for gonadotropin might reach the goal of a more patient-friendly and cost-effective treatment for IVF. Regarding higher response and efficacy of the present study, this administration mode could be employed in women with poor ovarian reserve and in women of poor or suboptimal ovarian response.Trial registration: None

The conception rates among women with premature ovarian insufficiency (POI) remain extremely low. To achieve a successful pregnancy, most of these women have to receive donor oocytes through IVF treatment. Ovarian administration of platelet-rich plasma (PRP) has been recently applied to enhance the ovulatory function in women with poor ovarian response. However, no live birth has been reported for this application in patients with POI. In this study, we present a 37-year-old woman with POI who had secondary amenorrhea for 6 months. The clinical manifestations and evaluation of this women with a diminished ovarian function were an undetectable serum level of AMH (<0.02 ng/mL) and an elevated serum level of FSH (63.65 mIU/mL). A single dose of autologous PRP (extracted from 40 mL of peripheral blood) in combination with gonadotropin (150IU rFSH/75 IU rLH) was directly injected into the stroma of bilateral ovaries via vaginal sonographic guidance. Following the treatment, this patient received controlled ovarian stimulation and IVF during the successive months. Following embryo culture, three cleavage-stage embryos were transferred, leading to a successful pregnancy, which later resulted in the live birth of twins. This case report provides one example of alternative therapy that allows POI patients to use autologous oocytes in IVF treatment.