Journal of

Clinical Medicine

Article
Does Serum LH Level Influence IVF Outcomes in Women
with PCOS Undergoing GnRH-Antagonist Stimulation:
A Novel Indicator
Jing Wang 1,† , Jinli Ding 1 , Bing Qu 2 , Yi Zhang 1, * and Qi Zhou 1, *

1 Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for
Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
2 Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
* Correspondence: zhangyi2008@[Link] (Y.Z.); clarence97zhou@[Link] (Q.Z.);
Tel.: +86-185-7145-5962 (Y.Z.); +86-136-2866-2997 (Q.Z.)
† First author.

Abstract: Objective: To explore the influence of LH levels on the IVF/ICSI outcomes in women
with PCOSundergoing GnRH-antagonist stimulation protocol. Methods: A total of 142 IVF/ICSI
patients in which the females were diagnosed with PCOS and underwent GnRH-antagonist protocol
for ovarian stimulation were enrolled. Patients were divided into three groups based on basal LH
(bLH) level, LH level on trigger day (hLH), and the ratio of hLH/bLH. The LH levels detected on
different days in the stimulation cycle as well as their relationships with the IVF/ICSI outcomes
were investigated. The main outcomes we observed were the number of oocytes retrieved, the
cumulative chemical pregnancy rate, clinical pregnancy rate, and live birth rate. Other factors
included the number of normally fertilized oocytes (2PN), top-quality embryo rate, and total Gn dose.
Results: There was no significant difference in the included outcomes and baseline characteristics
among different groups based on bLH levels. When patients were grouped according to hLH
Citation: Wang, J.; Ding, J.; Qu, B.;
levels (≤2 mIU/mL, 2–5 mIU/mL and ≥5 mIU/mL), we found decreased levels of basal FSH and
Zhang, Y.; Zhou, Q. Does Serum LH
LH in the group of hLH ≤ 2 mIU/mL than the other two groups. Then the ratio of hLH/bLH was
Level Influence IVF Outcomes in
calculated for each patient. Patients with hLH/bLH ≥ 1 had a higher top-quality embryo rate than
Women with PCOS Undergoing
GnRH-Antagonist Stimulation:
those with hLH/bLH between 0.5 and 1.0. Nevertheless, the cumulative clinical pregnancy rate
A Novel Indicator. J. Clin. Med. 2022, was significantly higher in the hLH/bLH ≤ 0.5 group than in the other two groups. Conclusions:
11, 4670. [Link] The study proposed the hLH/bLH ratio as a potential in predicting the influence of LH level on the
jcm11164670 embryo development potential as well as pregnancy outcomes in women with PCOS undergoing
GnRH-antagonist stimulation cycles.
Academic Editor: Jacek Szamatowicz

Received: 11 June 2022 Keywords: polycystic ovary syndrome; flexible GnRH antagonist protocol; luteinizing hormone;
Accepted: 4 August 2022 in vitro fertilization; intracytoplasmic sperm injection
Published: 11 August 2022

Publisher’s Note: MDPI stays neutral

with regard to jurisdictional claims in
published maps and institutional affil- 1. Introduction
iations. Polycystic Ovary Syndrome (PCOS) is a common endocrine disease that affects about
5–10% of females of reproductive age [1]. It is characterized by persistent anovulation,
hyperandrogenemia, and polycystic ovarian morphology, often accompanied by insulin
resistance. Insulin oversecretion promotes androgen synthesis and release in theca cells
Copyright: © 2022 by the authors.
by directly improving the effectiveness of Luteinizing Hormone (LH) and indirectly
Licensee MDPI, Basel, Switzerland.
increasing the pulse amplitude of LH. Based on the two cell–two gonadotropin theory,
This article is an open access article
Follicle Stimulating Hormone(FSH) and LH play a role in promoting follicular growth
distributed under the terms and
and maturation. LH and FSH are glycoproteins synthesized and secreted by the anterior
conditions of the Creative Commons
Attribution (CC BY) license (https://
pituitary gland. In the clinic, the levels of LH and FSH are normally used as indirect
[Link]/licenses/by/
evaluation indexes of ovarian reserve, whereas the ratio of LH and FSH is regarded as a
4.0/). predictor of ovarian responsiveness. The LH is essential for the structure and function

J. Clin. Med. 2022, 11, 4670. [Link] [Link]

J. Clin. Med. 2022, 11, 4670 2 of 8

of developing follicles. By inhibiting ovum maturation inhibitors during the early stage
of normal menstruation, the LH peak may stimulate the ovum to resume meiosis and
achieve final maturation by inhibiting ovum maturation inhibitors. Women with PCOS
had significantly higher LH levels and significantly lower FSH levels than normal healthy
women, resulting in significantly higher LH/FSH ratios, and increasing androgen synthesis
that consequently leads to hyperrecruitment of oocytes [2]. Hyperandrogenemia is driven
by both insulin resistance and hyperinsulinemia; it is not a necessary diagnostic condition
of PCOS, but an important clinical feature of most patients [3].
Low pregnancy rates in patients with PCOS may be due to excessive LH secretion
or premature LH surge before follicular maturation [4]. It was reported that LH surges
occur in approximately 20 to 26 percent of women with PCOS undergoing Controlled
Ovarian Stimulation (COS) cycles [5,6]. The elevated LH level in the follicular stage
is associated with decreased oocyte quality, early recovery of meiosis, and premature
ovulation of oocytes, resulting in a low implantation rate or increased abortion rate [7,8].
PCOS is a disease that affects women in their lives. Since women with PCOS have difficulty
ovulating spontaneously, most patients need ovulation induction to achieve pregnancy.
However, women with PCOS in various clinical centers, women with PCOS are at higher
risk of a series of adverse pregnancy outcomes such as gestational diabetes, gestational
hypertension, preeclampsia, eclampsia, premature delivery, and abortion after pregnancy
than healthy people due to the uneven management level [9]. Adverse pregnancy outcomes
in PCOS patients may be associated with hyperandrogenemia, hyperinsulinemia, abnormal
follicular development environment, and abnormal uterine and placental factors [10].
Women with PCOS are often affected by changes in GnRH secretion pattern, abnormal
negative feedback of estrogen progesterone, high androgen, hyperinsulinemia, obesity, and
other factors. Serum LH levels in women with PCOS are often increased and accompanied
by normal or low FSH levels. This results in an increased LH/FSH ratio, impaired follicular
maturation, and even infertility [11–13]. Previous studies have found that early LH peaks
in antagonist ovulation induction protocol influence oocyte and embryo quality and clinical
pregnancy outcomes [14,15]. Nonetheless, some studies have found that an abnormal
increase in LH during the ovulation process does not affect clinical outcomes; this disparity
in results may be due to population bias [16]. The objective of the present study was to
investigate the relationship between serum LH levels detected at different time points in
COS cycles and IVF/ICSI outcomes in women with PCOS such as the number of oocytes
retrieved, top-quality embryos, cumulative clinical pregnancy rate, and live birth rate.

2. Methods
2.1. Study Population
This retrospective study was approved by the Institutional Review Board of Renmin
Hospital, Wuhan University. IVF/ICSI cycles were reviewed from February 2019 to
November 2020 in Renmin Hospital of Wuhan University. Only women with PCOS
aged between 21 and 35 who underwent GnRH-antagonist stimulation protocol were
included. The diagnosis of PCOS was achieved if the patient met two of the following
criteria according to the Rotterdam ESHRE/ASRM Sponsored PCOS Consensus Workshop
Group [17]: (1) oligo- or anovulation, (2) clinical and/or biochemical signs of hyperandrogenism,
and (3) polycystic ovarian morphology on ultrasonography. The exclusion criteria included:
(1) congenital or acquired uterine anomalies; (2) history of ovarian surgery; (3) abnormal
parental karyotypes or medical conditions that contraindicated assisted reproductive
technology and/or pregnancy; (4) two or more previous recurrent spontaneous abortions;
(5) other known endocrine disorders; (6) previous medication of combined oral contraceptive
pills or glucocorticosteroids within 2–3 months before ovarian stimulation; And (7) repeated
cycles, i.e., one patient with more than one time of COH.
Patients were divided according to three different strategies, namely basal serum LH
level (bLH), LH level on HCG trigger day (hLH), and the ratio of hLH/bLH (Table 1).
J. Clin. Med. 2022, 11, 4670 3 of 8

Table 1. Grouping strategies.

bLH (mIU/mL) hLH (mIU/mL) hLH/bLH Ratio

Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 Group 1 Group 2 Group 3
≤5 5–10 ≥10 ≤2 2–5 ≥5 ≤0.5 0.5–1.0 ≥1
bLH: based on basal LH, hLH: LH level on trigger day.

2.2. Ovarian Stimulation Protocol

All patients had their first ultrasound scan on the second or third day of their
menstrual cycle, and blood samples were taken on the same day and measured for serum
level of FSH, LH, estradiol (E2 ), progesterone (P) and Anti-Mullerian Hormone (AMH).
The flexible protocol was carried out using recombinant follicle-stimulating hormone
(rFSH, Gonal-f, Merck Serono, Darmstadt, Germany) alone or in combination with hMG
(Lizhu Pharmaceutical Factory, Zhuhai, China). The gonadotropin (Gn) dose was adjusted
according to ovarian responses assessed by serum estrogen levels and ultrasonography.
After 4–5 days of Controlled Ovarian Hyperstimulation (COH), ultrasound examination
and measurement of serum FSH, LH, E2 and P were performed. When the leading follicle
reached the size of 12–14 mm in diameter, GnRH antagonist (Cetrorelix, Merck, Kenilworth,
NJ, USA) was injected at 0.25–0.5 mg/day based on the level of serum LH. When the
leading follicle was 18 mm or greater, final oocyte maturation was triggered by either
Human Chorionic Gonadotropin (HCG) (Lizhu Pharmaceutical Factory, China) alone or
with a dual trigger comprising 2000 IU HCG and GnRH agonist (Decapeptyl 0.2 mg, Ferring
International Center SA, Kiel, Germany).

2.3. Laboratory Procedures

The transvaginal ultrasonography was used to guide ovum pickup 34–36 h after hCG
administration. Depending on the quality of sperm, oocytes were inseminated either by
IVF or ICSI. Embryos were assessed and graded according to the criteria established by
the Istanbul consensus workshop [18]. Routinely, two good-quality embryos were vitrified
on the third day with the remaining cultured until blastocyst stage for subsequent Frozen
Embryo Transfer (FET) cycles.

2.4. Frozen Embryo Transfer (FET) Protocol and Luteal Phase Support
We chose frozen embryo transfer cycles to calculate cumulative chemical pregnancy rate,
clinical pregnancy rate, and live birth rate. In FET cycles, an artificial or natural protocol was
used for endometrial preparation. Embryo transfer was performed under transabdominal
sonographic guidance. For luteal support, we used intramuscular progesterone 40 mg
(Xianju Pharmaceutical Factory, Taizhou, China) and oral Duphaston (Abbott Healthcare
Products B.V., Weesp, The Netherlands) 30 mg once daily. If a positive pregnancy test was
observed, progesterone was continuously administered until 8–10 weeks of gestation.

2.5. Follow-Up Protocol and Outcomes

A blood test was performed 12 days after FET. Serum β-HCG > 10 IU/L was considered
as chemical pregnancy. Clinical pregnancy was defined as the presence of a gestational sac
with a fetal heart under ultrasonography 30–35 days after embryo transfer. All pregnant
women were monitored until live birth. The main IVF/ICSI outcomes measured include
the number of oocytes retrieved, cumulative chemical pregnancy rate, clinical pregnancy
rate, and live birth rate. The time period during which cumulative chemical pregnancy
rate, clinical pregnancy rate, and cumulative live birth rate were calculated was until
31 July 2021. Other analyzed outcomes in the present study mainly included the number
of 2PN, the ratio of top-quality embryos, and the total dosage of gonadotropins (Gn).
J. Clin. Med. 2022, 11, 4670 4 of 8

2.6. Statistical Analysis

The research results were systematized and analyzed using Statistical Package for
Social Sciences (SPSS) 22.0 software. The comparison of the arithmetic means of the
two samples was performed using t-test for independent samples or Mann–Whitney test,
depending on data distribution. The comparison of the frequency of attributive features
was performed by χ2 -test. The p value < 0.05 was considered as statistically significant.

3. Results
Patients’ Characteristics, Ovarian Stimulation Profiles and Outcomes
A total of 142 patients were included. Two (1.41%) cases developed mild to moderate
OHSS symptoms after oocyte retrieval, whereas no severe OHSS case was recorded. The
baseline information and outcomes were studied and compared under different grouping
strategies (Table 1). Briefly, there were no statistically significant differences in terms of age
and AMH levels among different groups in all of the three strategies.
There were no significant differences in baseline demographic characteristics and IVF
outcomes when the basal serum LH level was taken into account (Table 2).
Table 2. Characteristics and outcomes of patients grouped by basal LH.

Basal LH (mIU/mL)
Characteristics and Outcomes Group 1 (≤5) Group 2 (5–10) Group 3 (≥10)
p Value
(n = 65) (n = 54) (n = 23)
Age 28.85 ± 3.26 29.20 ± 3.63 29.09 ± 2.84 NS
AMH (ng/mL) 7.78 ± 3.51 8.39 ± 4.03 7.81 ± 3.12 NS
BMI (Kg/m2 ) 25.19 ± 3.99 24.66 ± 3.61 23.58 ± 3.44 NS
Total Gn dose (IU) 1902.50 ± 725.96 1665.57 ± 614.60 1660.87 ± 607.53 NS
Basal FSH (mIU/mL) 6.56 ± 2.05 6.76 ± 1.58 8.38 ± 1.56 NS
Basal LH (mIU/mL) 3.32 ± 1.06 6.76 ± 1.42 12.90 ± 2.88 -
Number of oocytes retrieved 17.97 ± 8.50 16.80 ± 7.51 18.00 ± 9.12 NS
Number of 2PN (n) 10.51 ± 5.82 9.02 ± 5.00 10.96 ± 7.48 NS
Ratio of top-quality embryos (%) 65.27 ± 27.95 67.81 ± 28.80 59.92 ± 34.10 NS
Cumulative chemical pregnancy rate (%) (n) 76.92 (50/65) 83.33 (45/54) 73.91 (17/23) NS
Cumulative clinical pregnancy rate (%) (n) 61.54 (40/65) 68.52 (37/54) 56.52 (13/23) NS
Cumulative live birth rate (%) (n) 23.08 (15/65) 31.48 (17/54) 17.39 (4/23) NS
NS: not significant.

The levels of LH on HCG day were investigated. When compared to the other two
groups, Group 1 (hLH ≤ 2 mIU/mL) had lower basal FSH and LH. The cumulative
chemical pregnancy rate was higher compared with that in Group 2 (hLH = 2–5 mIU/mL)
when hLH was less than 2 mIU/mL (Table 3).
Then the ratio of hLH to bLH was calculated for each individual and patients were
classified based on the ratio. The lowest BMI was observed when the ratio was no more than
0.5 (Group 1). Patients in the group with a hLH/bLH ≥ 1.0 (Group 3) consumed the most
dosage of Gn compared with those in the other two groups. In terms of IVF/ICSI outcomes,
the top-quality embryo rate was significantly higher in Group 3 than that in Group 2, whereas
the highest cumulative clinical pregnancy rate was recognized in Group 1. There was no
significant difference in the cumulative live birth rate among the three groups (Table 4).
J. Clin. Med. 2022, 11, 4670 5 of 8

Table 3. Characteristics and outcomes of grouped by LH on HCG day.

LH on HCG Day (mIU/mL)

Characteristics and Outcomes Group 1 (≤2) Group 2 (2–5) Group 3 (≥5)
p Value
(n = 68) (n = 48) (n = 26)
Age 29.03 ± 3.32 29.18 ± 3.59 28.88 ± 2.98 NS
AMH (ng/mL) 7.92 ± 3.72 7.81 ± 3.65 8.46 ± 3.61 NS
BMI (Kg/m2 ) 24.47 ± 3.96 25.21 ± 3.79 24.71 ± 3.41 NS
Total Gn dose (IU) 1872.70 ± 633.64 1650.26 ± 633.40 1898.94 ± 882.80 NS
Basal FSH (mIU/mL) 6.44 ± 1.75 a,b 7.26 ± 1.92 a 7.50 ± 2.07 b S
Basal LH (mIU/mL) 4.46 ± 2.41 c,d 6.70 ± 3.86 c 7.38 ± 4.72 d S
Number of oocytes retrieved 18.26 ± 8.61 16.31 ± 7.13 17.08 ± 8.98 NS
Number of 2PN (n) 10.63 ± 5.54 9.14 ± 5.56 9.85 ± 7.01 NS
Ratio of top-quality embryos (%) (n) 67.08 ± 25.27 61.25 ± 33.53 68.47 ± 30.02 NS
Cumulative chemical pregnancy rate (%) (n) 85.29 (58/68) e 69.39 (34/49) e 76.92 (20/26) S
Cumulative clinical pregnancy rate (%) (n) 69.12 (47/68) 55.10 (27/49) 61.54 (16/26) NS
Cumulative live birth rate (%) (n) 22.06 (15/68) 20.41 (10/49) 42.31 (11/26) NS
a–d : p > 0.05 between the two subgroups. That is, there is no statistical difference between the two groups;
e: p < 0.05 between the two subgroups; NS: not significant; S: significant differences were recognized (p < 0.05).

Table 4. Characteristics of patients grouped by hLH/bLH.

LH on HCG Day/Basal LH (Ratio)

Characteristics and Outcomes Group 1 (≤0.5) Group 2 (0.5–1.0) Group 3 (≥1.0)
p Value
(n = 87) (n = 37) (n = 18)
Age 28.93 ± 3.21 29.19 ± 3.64 29.11 ± 3.38 NS
AMH (ng/mL) 8.02 ± 3.46 8.12 ± 4.05 7.79 ± 3.85 NS
BMI (Kg/m2 ) 24.23 ± 3.80 f 25.11 ± 3.78 26.36 ± 3.30 f S
Total Gn dose (IU) 1707.16 ± 594.10 g 1635.47 ± 559.82 h 2354.72 ± 954.80 g,h S
Basal FSH (mIU/mL) 6.94 ± 1.91 6.91 ± 1.51 6.94 ± 2.64 NS
Basal LH (mIU/mL) 6.57 ± 4.07 6.02 ± 2.85 4.61 ± 3.22 NS
Number of oocytes retrieved 18.39 ± 8.67 16.78 ± 6.46 14.44 ± 8.56 NS
Number of 2PN (n) 10.64 ± 5.77 9.16 ± 5.79 8.72 ± 6.19 NS
Ratio of top-quality embryos (%) 66.68 ± 27.34 56.74 ± 34.15 i 76.81 ± 23.06 i S
Cumulative chemical pregnancy rate (%) (n) 85.06 (74/87) j 64.86(24/37) j 77.78 (14/18) S
Cumulative clinical pregnancy rate (%) (n) 70.11 (61/87) k,l 48.65 (18/37) k 55.56 (10/18) l S
Cumulative live birth rate (%) (n) 21.84 (19/87) 24.32 (9/37) 44.44 (8/18) NS
f–l : p < 0.05 between the two subgroups; NS: not significant; S: significant differences.

4. Discussion
In recent years, GnRH-antagonist therapy has been proposed as the first-line protocol
for COH in women with PCOS because antagonist can clearly reduce the risk of Ovarian
Hyperstimulation Syndrome (OHSS) [19–21]. However, excessive increase and decrease of
LH are inevitable in the process of GnRH-antagonist protocol. The early LH peak during
ovulation induction usually refers to the endogenous LH peak before follicular maturation
or when the follicular diameter line does not reach the HCG injection standard. A key
step in COH is the competitive binding of GnRH-antagonist to GnRH receptors on the
pituitary gland and the inhibition of endogenous premature LH peak. Nevertheless, GnRH-
antagonist can reduce but does not completely prevent the occurrence of early LH peaks,
and women with PCOS with elevated basal LH levels generally have a higher incidence
of early LH elevation (LH ≥ 10 U/L) during GnRH-antagonist protocol. That raises the
question of how the serum LH affects the outcome of IVF/ICSI and whether there is a
potential indicator to evaluate the influence.
Women with PCOS are a potential high-reaction population, an antagonist protocol
being able to greatly reduce the risk of OHSS through GnRH agonist trigger, while the
clinical pregnancy outcome is not affected. Therefore, at present, antagonist protocols have
J. Clin. Med. 2022, 11, 4670 6 of 8

become the main ovulation induction protocol chosen by women with PCOS. The control
of serum LH levels in the GnRH-antagonist protocol is an important factor in ovulation
induction therapy, since women with PCOS are usually accompanied by higher basal
LH levels and an increased probability of early LH elevation. Early LH peak can cause
premature ovulation and luteinization of follicles, which can affect the number of retrieved
oocytes, oocyte and embryo quality, and endometrial receptivity.
In this study, subjects were divided according to three different strategies based on
LH levels detected on different days in the stimulation cycle. Generally speaking, there
were statistical differences in some outcomes among different groups under each strategy.
Since all the patients had frozen embryo transplantation, the effect of the hormone level
on the endometrial receptivity could be ignored. The level of basal LH did not affect the
number of oocytes retrieved, top-quality embryo rate, clinical pregnancy rate, and live
birth rate in IVF/ICSI according to the findings. When hLH was considered, we found
an increase in cumulative chemical pregnancy rate in the group of hLH no more than
2 mIU/mL. Moreover, when the bLH/hLH ratio was applied, there were more significant
differences in embryo quality and pregnancy rate. Factors related to the outcomes in a FET
cycle include embryo development potential, endometrium preparation protocol, demo-
graphic characteristics of patients, and underlying disease that could interfere with embryo
implantation and intrauterine development. When we discussed the influence of hLH/bLH
in the fresh cycle on the pregnancy outcome in the FET cycle, we assume it attributed to the
embryo development potential. Even though the hLH/bLH 1.0 group had the highest rate
of top-quality embryos, the pregnancy rate was highest in the <0.5 group, indicating that
embryo development was highest in the <0.5 group. Embryo grading cannot be exactly
the same as the embryo’s developmental potential; this may also be related to the patient’s
endometrial receptivity and occult underlying diseases. The index hLH/bLH reflects the
dynamic change of LH between HCG day and early follicular phase. We’ve noticed that
both the <0.5 group and 0.5–1.0 group have a basal LH level at around 6 mIU/mL while
that value was 4.6 mIU/mL in the ≥1.0 group, which means that the corresponding LH
level on HCG day should be <3 mIU/mL, 3–6 mIU/mL, and ≥4.6 mIU/mL, separately. In
that sense, the decrease in embryo development potential in the 0.5–1.0 and ≥1.0 groups
may be related to the high LH exposure during stimulation. However, when analyzing
the basal LH and HCG-day LH levels separately, we did not achieve such a statistically
significantly difference, even though there was a trend of increase in pregnancy rate in
hLH ≤ 2 group.
It was also found that when hLH/bLH was greater than 1.0, patients consumed the
most gonadotropin; thus, the cost was the highest. This may be because the BMI of this
group of patients was the highest, which can also indicate that patients with high BMI
among women with PCOS also have relatively high LH levels and high LH level is an
important cause of reproductive dysfunction in women with PCOS.
Early increase of serum LH level is usually associated with high incidence in elderly
patients with low ovarian storage or patients with high response, and it should be noted
that different effects of elevated serum LH level on pregnancy outcome in different groups.
Although women with PCOS are also highly reactive population, their internal secretion
and metabolic characteristics are different. Women with PCOS are usually have elevated
basal LH levels, high androgen levels, and high insulin resistance, resulting in increased
expression of insulin-like growth factor, which promotes the LH receptor expression.
However, the biological activity of LH receptor and its clinical significance need to be further
clarified. Currently, there is no unified standard for defining the early-onset LH peak, and
most studies believe that the early-onset LH peak is defined as LH ≥ 10 U/L before follicular
maturation, with or without progesterone elevation [15]. The simultaneous elevation of
serum LH and progesterone levels with premature follicular luteinization usually affect
oocyte and embryo quality and endometrial receptivity; however, the increased LH level
usually occurs when the follicular meridian is relatively small. Because there are fewer LH
receptors on follicular granulosa cells, it is impossible to respond to the increased LH level;
J. Clin. Med. 2022, 11, 4670 7 of 8

usually, increasing the dose of antagonist can reduce LH to the normal level. Women with
PCOS are predisposed to early LH elevation, particularly those with high BMI and basal
LH levels. Obesity has also been linked to an early LH peak in previous studies [22].
In summary, our study showed that the fluctuation in serum LH level in GnRH-
antagonist protocol could interfere with pregnancy outcomes in PCOS women receiving
IVF/ICSI treatment and the ratio of hLH/bLH could be a more sensitive indicator for
evaluating the LH level on the embryo development potential in women with PCOS
in a GnRH-antagonist protocol. However, due to the retrospective nature of this study,
particularly the small number of cases of frozen embryo transfer included, there may be
selection bias, and its clinical conclusions have certain limitations. Future studies will
increase the number of women with PCOS to further study the impact of LH level on
outcomes of IVF/ICSI, especially cumulative live birth rate. This will better clarify its
impact on the outcome of IVF/ICSI, though further studies are still needed to confirm this
conclusion.

Author Contributions: J.W., Y.Z. and Q.Z. contributed to the conception of the study; J.W. and B.Q.
performed data collection; J.W., J.D. and Y.Z. performed the data analyses and wrote the manuscript;
J.W., Y.Z. and Q.Z. helped perform the analysis with constructive discussions. All authors have read
and agreed to the published version of the manuscript.
Funding: This study was supported by Natural Science Foundation of Hubei Province (2018CFB422),
Natural Science Foundation of Hubei Province (2020CFB254), Natural Science Foundation of Hubei
Province (2021CFB123) and Fundamental Research Funds for the Central Universities (2042021kf0082).
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki, and the protocol was approved by the Ethics Committee of the Renmin Hospital of
Wuhan University (Ethical approval number: WDRY2019-K077).
Informed Consent Statement: Patients signed informed consent regarding publishing their data.
Data Availability Statement: The datasets generated during and/or analyzed during the current
study are available from the corresponding author on reasonable request.
Conflicts of Interest: The authors declare no conflict of interest.

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