IVF Outcomes of Patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China

doi:10.21203/rs.3.rs-2463777/v1

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IVF Outcomes of Patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China

https://doi.org/10.21203/rs.3.rs-2463777/v1

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published 14 Apr, 2023

Read the published version in BMC Pregnancy and Childbirth →

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Background: Isolated Hypogonadotropic Hypogonadism (IHH) is a rare reproductive disorder due to the dysfunction of the gonadotropin-releasing hormone axis. Without an exogenous hormone supplement, patients with IHH typically fail to enter or develop through puberty and retain infertility. This study was conducted to 1) address the population characteristic of IHH and their clinical outcomes who underwent IVF treatment, 2) evaluate the predictor for the ovarian response for IHH.

Methods: This retrospective cohort study included 83 women with IHH who underwent fresh ART cycles and non-diagnosed controls (n=676). The receiver operating characteristic curves were generated to assess the predictor for the ovarian response. The IVF outcomes and strategy patterns administered in IHH were investigated in univariate and regression analyses to optimize the live birth rate.

Results: The fertilization rate and 2PN rate in both fertilized methods (IVF and ICSI) were significantly higher in IHH groups, as was the number of transferable embryos. The highest clinical pregnancy (CP) rate was seen in IHH with a high ovarian response group (63.6%), followed by patients with normal ovarian response in controls. Among patients diagnosed as CP, significantly more live births were observed in IHH groups, even subdivided by the ovarian response. For high ovarian response, AMH levels were the most accurate and reliable predictor (ROC = 0.871). Among IHH patients, the initial Gn dose was significantly lower in CP groups than in non-CP. AMH was the negative factor for initial Gn and total Gn, while AFC was a positive factor in the duration of Gn use.

Conclusions: The study findings suggest patients with IHH were good responders to IVF treatment and the lower initial Gn dosing needs to be considered for normal ovarian responders in IHH. AMH was the best-performed predictor for the ovarian response. The "low and slow" Gn dosing protocol for IHH was practicable with a satisfied IVF outcome in the clinic.

Isolated Hypogonadotropic Hypogonadism

Infertility

AMH

Clinical pregnancy

Ovarian response

Idiopathic hypogonadotropic hypogonadism (IHH, MIM147950) is a rare genetic disease, occurring in 1:29,000 males and 1:125,000 females (1). The hallmark of IHH is absent pubertal development, hypogonadotropism and infertility. Commonly, at the expected time of puberty, gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is amplified, resulting in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from the pituitary. In IHH, GnRH action and/or secretion is typically disturbed, failing to initiate puberty (2). Patients have low sex steroids and "inappropriately" low LH and FSH (hypogonadotropic). Untreated patients remain sexually infantile and are infertile. Assisted reproductive technology (ART) is needed as an optional and compelling opportunity for IHH patients with reproductive desires. However, only a few studies were reported on reproductive capacity and IVF treatment outcomes in IHH due to the rarity of the disease prevalence.

Pulsatile gonadotropin-releasing hormone (GnRH) treatment was an appropriate way to simulate the normal menstrual cycle to regain ovarian function for IHH patients (3). Nevertheless, the inconvenience of wearing the electronic pump and consequent psychological problems were concerned. Using injectable gonadotropins (Gn) in patients with IHH is more suitable and acceptable as a treatment protocol. With a limited understanding of ovarian response to Gn in IHH, the balance of optimizing the Gn dosing and reducing inadvertent hyperstimulation (ovarian hyperstimulation syndrome, OHSS) constantly challenges clinical practice.

Likewise, ovarian response, especially the predictor of ovarian response in IHH, has not been precisely and systematically studied in this setting. This paper is the first study that evaluated the well-performed predictors for ovarian response in the IHH population. The aims of this study were 1) to depict the population characteristics, including IVF outcomes and clinical pregnancy outcomes, and 2) to discover the best predictors for ovarian response markers, thus benefit the physicians’ choice for the proper IVF protocol and optimized dose of Gn administration.

The studies involving human participants were reviewed and approved by the Ethics Committee of Peking University Third Hospital. This study did not require informed consent for participation by the national legislation and institutional requirements.

Patients

This retrospective cohort study included 115 women with IHH who underwent oocyte retrieval between January 2010 and October 2021 at the Reproductive Center of Peking University Third Hospital. To be enrolled in the study, isolated hypogonadotropic hypogonadism (IHH) was defined as previously published (2, 4). In brief, IHH was defined as: i) absent/incomplete sexual maturation; ii) serum estradiol < 73.4 pmol/L in women in the setting of low or normal levels of serum gonadotropins; iii) no functional reason for hypogonadism. Among the 115 women with IHH, 83 IHH patients with detailed clinical information in IVF cycles were recruited in this study.

The inclusion criteria of all 676 patients in the control group were: i) with infertility due to male factors, tubal factor or idiopathic causes (excluded with endometriosis, adenomyosis and polycystic ovarian syndrome); ii) using ultra-long GnRH-a protocol; iii) matching characteristics with IHH group (including age, partner’s age, BMI, infertility duration, fertilization method). (Fig. 1).

Controlled Ovarian Stimulation (COS) Protocols

In IHH patients, more than two cycles of pretreatment with HRT were performed before the super ovulation to provide endometrial regeneration. Then they received daily urinary gonadotropin for injection (HMG, Livzon, China) with or without recombinant human FSH for injection (rFSH, Gonal-F, Merck Serono, Germany).

The ultra-long GnRH agonist (GnRH-a) protocol was performed in the control group. First, Triptorelin Acetate (Diphereline, Ipsen, France) with a dose of 1.8 mg or 3.75 mg was administered in the early- follicular phase or mid-luteal phase of the last menstrual period. After 28 or 35 days, patients were monitored by hormone tests and ultrasound. After meeting the criteria of pituitary suppression, rFSH was administered.

When at least two dominant follicles (diameter ≥ 18mm) developed, all patients were triggered by either 10000 IU human chorionic gonadotropin (HCG, Livzon, China) or 250 ug recombinant HCG for injection (rHCG, Ovidral, Merck Serono, Germany). Thirty-six hours later, the oocyte retrieval procedure was performed under transvaginal ultrasound. On the same day, IVF or ICSI was performed according to the evaluation of semen analysis. After 3 or 5 days of oocyte retrieval, embryo transfer (ET) was performed with two embryos or one blastocyst. Clinical pregnancy is defined as a gestational sac in which a fetal heartbeat is detected by ultrasound 28 to 30 days after embryo transfer.

Cycle Outcomes

Cycle characteristics, including overall gonadotropins (tG) administered, initial gonadotropins (iG) administered, estrogen levels on the day of ovulation triggering (maxE2), and endometrial thickness on hCG day, were recorded. Moreover, cycle outcomes, including the number of oocytes retrieved, two pronuclei (2PN) fertilized oocytes, number of transferred embryos, fertilization method, endometrial thickness, and cause of cancellation of cycles, were investigated. The obtained ovarian response was defined as < 5 oocytes retrieved, 5–15 oocytes retrieved, and༞15 oocytes retrieved for the low response, normal response, and high ovarian response, respectively.

Data analysis

Statistical analysis was performed using GraphPad Prism 9.4.0. Normally distributed data were presented as mean ± Sd, and Non-normally distributed data were presented as median ± quartile. To evaluate the markers for predicting ovarian response in IHH, receiver operating characteristic (ROC) curves were performed. The IVF outcomes comparison in IHH and controls were performed using Fisher Exact Test or Chi-square test. Linear regression was used to identify the independent factors related to AMH, and a P-value of 0.05 was considered significant.

All COS Cycles

Demographic and basal characteristics and ART outcomes of 83 women in the IHH group and 676 women in the control group are shown in Table 1. The patient's age, BMI, and partner's age were similar between both groups. All basal hormone and AMH levels were significantly lower in the IHH group, while no differences were observed in the AFC. Similar cycle characteristics, including initial Gn dosage (iGn), maximal E2 (MaxE2) levels and endometrial thickness, were observed in IHH and controls. Interestingly, the patients with IHH were observed to have a significantly higher MaxE2 level per oocyte retrieved, suggesting a higher ovarian quality in IHH, and also required a longer duration of stimulation and larger total Gn dosage (tGn) than the control group. The mean number of oocytes retrieved per cycle (11 versus 12; =0.539) and ovarian response were similar between groups, as were the fertilization method, mean number of fertilized embryos, and 2PN embryos. Notably, fertilization rate and 2PN rate in both fertilized methods (IVF and ICSI) were significantly higher in IHH groups compared with the control group, as was the mean number of transferable embryos. Sixty-six of 83 women with IHH and 456 of 676 women in the control group underwent embryo transfer (ET) and were further examined in the clinical pregnancy-related analysis (Table 1 and Fig. 1). A higher ET rate was seen in the fresh cycle in the IHH group compared with the controls (P = 0.03). Similar causes for cancellation of ET were seen between groups, and prevention for the ovarian hyper-stimulation syndrome (OHSS) for those patients predicted to be high risk was the primary causation. The clinical pregnancy (CP) rate and live birth (LB) rate did not differ between groups. However, among patients diagnosed as clinical pregnancy, significantly more live birth was observed in IHH groups (P = 0.02) with only one spontaneous loss of fetus at six weeks of gestation.

Ovarian Response in IHH

To explore the ovarian response, patients were classified into three groups by the number of oocytes retrieved (Table 2). There was no significant difference in BMI, basal FSH, duration of stimulation, and endometrial thickness among all three groups. The patient's ages in the low ovarian response group were older than the other groups (P༜0.001). AMH levels, AFC and MaxE2, were observed significantly increase from the low ovarian response group to the high ovarian response group. At the same time, tGn showed a significantly decreased trend (as the P value shown in Table 2). In the low ovarian response group, a higher dose of iGn was administered than in the other group.

ROC curves were used to evaluate the performance of various factors that affect ovarian reservation to predict ovarian response (Fig. 3). Of all the candidate markers, AMH achieved the highest AUC [0.871 (0.722, 1.00)] for the high ovarian response, representing the best power to predict the ovarian response in IHH with an AMH cut-off value of > 4.020. The AUCs of other markers, including AFC, FSH, iGn, and tGn, were 0.656, 0.526, 0.610,0.713, respectively (Supplementary Table 2). Notably, only the factors with AUC over 0.7, AMH, and tGn, were statistically significant (P = 0.002, 0.003). These two factors and iGn performed well in predicting low ovarian response, although the small sample size should be considered (Supplementary Table 1, Supplementary Fig. 1).

The regression model of each variable in all IHH patients, including patients' age, AMH, FSH, and tGn, demonstrated only AMH remaining as a significantly positive factor (P < 0.001, slope = 0.14, 95% CI 0.07–0.22, Table 3). In the further analysis of the linear regression model according to ovarian response, no factors were shown to affect the oocyte retrieved (Supplementary Table 2). In addition, higher live birth rates were seen in the IHH group, especially in those women with a high ovarian response (Supplementary Table 3).

Clinical Pregnancy in IHH

To further determine the main factors affecting clinical pregnancy outcomes in the IHH cohort, 66 of 83 women in the IHH group who underwent ET(IHH-ET) were included (Table 4). There is no difference in age, BMI, and ovarian response between the clinical pregnant and non-pregnant groups in IHH. The iGn was significantly lower in the clinical pregnant IHH group. The basal FSH, tGn, maxE2, and duration of stimulation were similar between groups. As expected, AMH level and MaxE2/etotal were higher in clinical pregnant patients compared with non-pregnant patients (2.6 ± 1.58, 2.15 ± 1.17 ng/ml, P = 0.34; 752.8 ± 448.4, 736.1 ± 357.6, P = 0.78), while with no statistical significance.

A binary logistic regression model was performed to identify the independent factors that affect clinical pregnancy in IHH (including patient age, AMH level, AFC, iGn, tGn, and MaxE2) (Supplementary Table 4). Interestingly, iGn was the only significant variable (P = 0.019) showing the effect on clinical pregnancy in patients with IHH. The same model was used for patients with a high ovarian response (receiving oocytes > 15 in this fresh cycle), with AMH, AFC and tGn being the significant variables, respectively (Supplementary Table 4).

According to the observation of the bubble plot of IHH-ET patients (Fig. 2), a linear regression model of each factor for the usage of Gn in the cycle (including iGn, tGn and duration of Gn used) was performed. As expected, the result showed that AMH was the significant factor for iGn and tGn, reducing the dosage of Gn by 22.3IU and 196.2IU for increasing the value of AMH by one, respectively. Conversely, patients' age acted as a significant positive factor in iGn and tGn, increasing 10.47IU and 149.4IU for an additional year (Table 5). Additionally, AFC was the only factor correlated with the duration of Gn use in the cycles in this analysis. This finding suggests the increased need for adaptation time of launching Gn for more potential “dynamic” oocytes.

In this cohort study, serum AMH was demonstrated to be a well-performed predictor for ovarian response in IHH patients. Compared with patients with a proper ovarian reserve function, a satisfied IVF outcome and lower OHSS occurrence were observed in IHH, providing the Gn dose reference for IVF treatment in the future. AMH levels were significantly lower in IHH patients, while the higher fertilization rate and the number of transferable embryos indicate that adequate gonadotropins could reboot the “dormant” status of antral follicles and nourish them to mature oocytes in IHH patients.

IHH, a rare genetic disorder, is characterized by a failure of GnRH secretion or action resulting in the inability to enter or progress through puberty and retaining sexual infantilism and infertility in the absence of exogenous hormone supplements (5, 6). Accurate interpretation of evidence-based clinical information and discovering efficient and safe Gn dosing are critical for current clinical care and counseling of patients with rare disorders in IVF treatment. However, owing to the rarity of IHH, only limited cohort studies were published before, and the management of women with IHH is still not standardized (7) with the difficulties in early identification and prompt transition of clinical care. Thus, the first aim of this study was to address the IVF outcomes in one of the largest cohorts with IHH and determine the valuable findings to further provide clinical curation of IHH.

As expected, IHH patients have observed higher Gn consumption and longer treatment duration with varied causes of infertility, including male factor, tubal factor, and unexplained factor, in line with previous reports (8–12). Despite the CP rate and LB rate being similar in IHH and matched control groups, the higher fertilization rate, ET rate and transferable embryos were validated in IHH patients in our study, which was against the previous study (9). This result suggests that the development and maturation of oocytes were temporally "switched off" instead of "cutting off" in IHH and could be aroused by the proper amount and sufficient treated period of pituitary hormone. In agreement with this point, the higher MaxE2/etotal and lower pregnancy loss rate (2.7%) in the IHH group were displayed in this study, which lowered from previous reports from different study groups with the declaration of pregnancy loss occurrence in 17.1–19.7% after IVF/ICSI (13–15). This finding highlights that women with IHH could potentially regain reproductive function and respond very well to exogenous gonadotropins with a high quality of oocytes/embryos. Thus, assessment of ovarian response in the IHH cohort to COS is of utmost importance for achieving satisfied IVF outcomes (i.e., ET rate and LB rate) and simultaneously avoiding COS-associated complications.

The next question that comes to mind is how to measure the ovarian response of patients with HH. Hypogonadism, ovarian infantilism and anovulation challenged the baseline test for hormonal levels and other ovarian response-related factors (i.e., AFC) in IHH. Although AMH is identified as a valuable marker of ovarian reserve in reproductive-aged women (16, 17), the debate on whether serum AMH could serve as a prognostic marker of fertility in IHH remains untacked. Despite a small sample size (n = 12), an earlier study proposed that AMH appears as a promising marker of ovarian response in patients with IHH undergoing IVF (18), which was consistent with this current study. However, the emerging evidence pointed out that AMH is fluctuated and is not gonadotropin-independent throughout folliculogenesis (19, 20). When priming with a period of Gn, the lower level of AMH in IHH women can be reversed by follicle-stimulating hormone (21), suggesting AMH levels may underestimate ovarian reserve due to the lack of FSH-dependent growing follicles. Thus, aware of the complexity of AMH dynamics, the current study with a fresh look, discovered a satisfactory ovarian response and highlighted that AMH was superior to other markers to predict either low or high response.

Nevertheless, AMH should be cautiously used in assessing the primordial follicle pool and prognosticating the outcome of IVF, especially in gonadotropin-deficient states. Low AMH in IHH should not be judged as a reflection of poor ovarian reserve, as gonadotropin administration can effectively restore fertility. The higher CP rate and LB rate in IHH with a high ovarian response may reflect the reversal in IHH, which means the patients with IHH later achieve activation of their hypothalamic-pituitary-gonadal axis with regain the ability in gametogenesis(22). These patients may retain partially active reproductive endocrine function or potential at the “dormant phase.” It is possible that the dynamic nature of the HPG axis renders them susceptible to exogenous gonadotropins supplement/stimulation (22, 23).

Interestingly, in univariate analyses of cycles in IHH-ET, a significant difference was observed in the iGn. Lower iGn was commonly used in the CP group in IHH, even though there was no difference in the distribution of patients with varied ovarian responses. In this study, the gonadotropin for starting the COS ranged from 150 IU to 300 IU (covering 84.8% of cases). A similar strategy pattern for iGn using a usual dosage (150 IU, 150 IU to 450 IU, and 315 IU) was presented in earlier studies(9–11). In comparison, another group attempted to start at 450 IU to 600 IU with a step-down regimen. The high dose of iGn did not come along with satisfying clinical outcomes, shortened Gn treatment, and decreased tGn. From this standpoint, the resurrection stage of the fertile status IHH comprises a series of adaptations as a "boiling frog in warm water" phenomenon.

Further analysis of the usage of Gn dosing in IHH-ET was performed to discover the core contributor to defining treatment management in clinical practice. AMH and patient age-based Gn dosing was commonly used in our infertility center, whereas AFC was more referred significantly to treatment duration. So far, under the present treated protocol, a satisfied IVF outcome was observed in the IHH cohort with a similar etotal, CP rate and LB rate compared with the non-IHH cohort. It was convinced that the pregnancy rate would climb by reaching the embryo transfer stage in an aged HH patient. It was no difference in the cancellation rate for the high risk of hyperstimulation in IHH and controls, yet only one patient with mild OHSS occurred in the IHH group. To retrieve adequate oocytes and avoid COS-related complications, individualized protocol raises attention to the clinic due to the effectiveness of treatment during IVF. Individualized dosing based on AMH or AFC reduced the occurrence of mild and moderate OHSS (24, 25). Therefore, more cohort study needs to be completed to estimate the power of individualized dosing protocol in IHH.

The strength of this study is the great benefit of the large size of the IHH cohort worldwide, allowing us to dissect the information from different aspects and to explore the population features in IVF procedure, including the ovarian response, CP outcomes and efficient Gn use. Notably, considering the unique biological nature of IHH, only the ultra-long GnRH-a protocol was discussed in the control group, inducing a hypogonadotropic state, which was absent in previous studies. Some limitations need to be addressed. First, owing to the concern of inherent biases of discrepancy of patients’ data in different cycles, the fact that only the first fresh cycle was investigated in this study is a potential weakness. The hormone supplement could reverse the hypo-status in IHH, and the impact would be heterogeneous in patients. Second, even though our results were convincing to provide a numerical Gn dose reference, the safety management of individualized dosing still needs more studies and data accumulation to give the ultimate answer.

Patients with IHH were good responders to IVF treatment, and lower initial Gn dosing properly may benefit their clinical pregnancy. AMH was the best-performed predictor for ovarian response. The "low and slow" Gn dosing protocol for IHH was practicable with a satisfied IVF outcome in the clinic. The optimal and individualized protocol designation, dosage and regimens for fertile induction need further study for women with IHH.

Acknowledgments: The authors have nothing to declare.

Author Contributions: I) Conception and design: J.Q, R.L and W.X.(II) Administrative support: J.Q, R.L. (III) Provision of study materials or patients: W.X. (IV) Collection and assembly of data: W.X. (V) Data analysis and interpretation: W.X. (VI) Manuscript writing: All authors. (VII) Final approval of manuscript: All authors

Funding: This work was supported by the National Key Research and Development Project of China (2022YFC2702502) and the National Natural Science Foundation of China (81925013, 82288102).

Availability of data and materials: The raw data supporting this study can be requested from the corresponding author.

Ethics approval and consent to participate: This study was approved by the Institutional Review Board of the Peking University Third Hospital. Written informed consent was obtained from patients or their representatives for participation in this study. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for publication: Not applicable.

Competing interests: The authors declare that they have no competing interests

Laitinen EM, Vaaralahti K, Tommiska J, Eklund E, Tervaniemi M, Valanne L, et al. Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland. Orphanet J Rare Dis. 2011;6:41.
Balasubramanian R, Crowley WF. Jr. Isolated GnRH deficiency: a disease model serving as a unique prism into the systems biology of the GnRH neuronal network. Mol Cell Endocrinol. 2011;346(1–2):4–12.
Crowley WF Jr, McArthur JW. Simulation of the normal menstrual cycle in Kallman's syndrome by pulsatile administration of luteinizing hormone-releasing hormone (LHRH). J Clin Endocrinol Metab. 1980;51(1):173–5.
Kallmann F. The genetic aspects of primary eunuchoidism. Am J Ment Defic. 1944;48:203–36.
Balasubramanian R, Crowley WF. Jr. Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, editors. GeneReviews((R)). Seattle (WA)1993.
Stamou MI, Cox KH, Crowley WF. Jr. Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the "-Omics" Era. Endocr Rev. 2015;36(6):603–21.
Boehm U, Bouloux PM, Dattani MT, de Roux N, Dode C, Dunkel L, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism–pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547–64.
Ulug U, Ben-Shlomo I, Tosun S, Erden HF, Akman MA, Bahceci M. The reproductive performance of women with hypogonadotropic hypogonadism in an in vitro fertilization and embryo transfer program. J Assist Reprod Genet. 2005;22(4):167–71.
Ghaffari F, Arabipoor A, Lankarani NB, Etminan Z, Tehraninejad ES. Assisted reproductive technique outcomes in hypogonadotropic hypogonadism women. Ann Saudi Med. 2013;33(3):235–40.
Yilmaz S, Ozgu-Erdinc AS, Yumusak O, Kahyaoglu S, Seckin B, Yilmaz N. The reproductive outcome of women with hypogonadotropic hypogonadism undergoing in vitro fertilization. Syst Biol Reprod Med. 2015;61(4):228–32.
Kumbak B, Kahraman S. Women with hypogonadotropic hypogonadism: cycle characteristics and results of assisted reproductive techniques. Acta Obstet Gynecol Scand. 2006;85(12):1453–7.
Lewit N, Kol S. The low responder female IVF patient with hypogonadotropic hypogonadism: do not give up! Fertil Steril. 2000;74(2):401–2.
Sunderam S, Kissin DM, Crawford SB, Folger SG, Jamieson DJ, Warner L, et al. Assisted Reproductive Technology Surveillance - United States, 2014. MMWR Surveill Summ. 2017;66(6):1–24.
Tummers P, De Sutter P, Dhont M. Risk of spontaneous abortion in singleton and twin pregnancies after IVF/ICSI. Hum Reprod. 2003;18(8):1720–3.
Yang AM, Xu X, Han Y, Wei JJ, Hao GM, Cui N, et al. Risk Factors for Different Types of Pregnancy Losses: Analysis of 15,210 Pregnancies After Embryo Transfer. Front Endocrinol (Lausanne). 2021;12:683236.
Iliodromiti S, Anderson RA, Nelson SM. Technical and performance characteristics of anti-Mullerian hormone and antral follicle count as biomarkers of ovarian response. Hum Reprod Update. 2015;21(6):698–710.
Cedars MI. Evaluation of Female Fertility-AMH and Ovarian Reserve Testing. J Clin Endocrinol Metab. 2022;107(6):1510–9.
Sonmezer M, Ozmen B, Atabekoglu CS, Papuccu EG, Ozkavukcu S, Berker B, et al. Serum anti-Mullerian hormone levels correlate with ovarian response in idiopathic hypogonadotropic hypogonadism. J Assist Reprod Genet. 2012;29(7):597–602.
Tran ND, Cedars MI, Rosen MP. The role of anti-mullerian hormone (AMH) in assessing ovarian reserve. J Clin Endocrinol Metab. 2011;96(12):3609–14.
Chan C, Liu K. Clinical pregnancy in a woman with idiopathic hypogonadotropic hypogonadism and low AMH: utility of ovarian reserve markers in IHH. J Assist Reprod Genet. 2014;31(10):1317–21.
Bry-Gauillard H, Larrat-Ledoux F, Levaillant JM, Massin N, Maione L, Beau I, et al. Anti-Mullerian Hormone and Ovarian Morphology in Women With Isolated Hypogonadotropic Hypogonadism/Kallmann Syndrome: Effects of Recombinant Human FSH. J Clin Endocrinol Metab. 2017;102(4):1102–11.
Sidhoum VF, Chan YM, Lippincott MF, Balasubramanian R, Quinton R, Plummer L, et al. Reversal and relapse of hypogonadotropic hypogonadism: resilience and fragility of the reproductive neuroendocrine system. J Clin Endocrinol Metab. 2014;99(3):861–70.
Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA, et al. Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med. 2007;357(9):863–73.
van Tilborg TC, Oudshoorn SC, Eijkemans MJC, Mochtar MH, van Golde RJT, Hoek A, et al. Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis. Hum Reprod. 2017;32(12):2485–95.
Lan VT, Linh NK, Tuong HM, Wong PC, Howles CM. Anti-Mullerian hormone versus antral follicle count for defining the starting dose of FSH. Reprod Biomed Online. 2013;27(4):390–9.

Tables 1 to 5 are available in the Supplementary Files section.

No competing interests reported.

Table1.xlsx
Table2.xlsx
Table3.xlsx
Table4.xlsx
Table5.xlsx
SupplFigure1.tif
Supplementary Figure 1. ROC curves of selected factors in COS cycles to predict low ovarian response
SupplementaryTables.xlsx
Tables and Supplementary Tables are attached in excel format.

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IVF Outcomes of Patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China

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Abstract

Figures

Introduction

Materials And Methods

Patients

Controlled Ovarian Stimulation (COS) Protocols

Cycle Outcomes

Data analysis

Results

All COS Cycles

Ovarian Response in IHH

Clinical Pregnancy in IHH

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

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